CRC Croce Tili List of patients for mir125b Metabolomic study Clinical data update 13/01/12

AGGRESSIVE CRC Croce Tili List of patients for mir125b Metabolomic study Clinical data update 13/01/12 INDOLENT Table S1. Clinical data of the patients used for the study ID ZAP %VH WBC Dx date First TX if No Tx Last FU Last Sample Date Latest FollowUp DaDate of Death ID ZAP %VH WBC Dx date First TX if No Tx Last FU Last Sample Date Latest FollDate of Death 1 JCB0217 46.7 100 39.5 01/05/01 01/01/05 22/11/10 22/11/10 1 TJK0829 1.1 93.1 18.5 26/09/07 18/01/11 25/10/11 25/10/11 2 JCB0175 50.1 100 149 02/02/00 01/08/03 22/02/11 21/02/09 2 TJK0540 9.7 91.7 27.9 01/01/95 30/08/11 16/11/07 04/01/11 3 TJK0563 56.6 100 10 06/05/05 04/01/07 29/02/12 29/02/12 3 JGG0012 0.9 94 152.5 01/02/94 29/09/11 29/03/12 29/09/11 4 TJK0498 82.2 100 35.1 01/10/03 05/02/07 20/12/11 20/12/11 4 JGG0015 0.5 93.1 61.5 01/07/99 01/04/10 28/07/11 22/09/11 5 TJK0437 89 100 12.5 01/11/03 09/07/06 01/07/08 28/09/08 28/09/08 5 TJK0083 4.3 94.4 231 25/02/92 17/05/04 10/08/09 10/08/09 6 MJK1200 81.1 99.7 155.1 29/12/05 05/02/07 29/01/07 29/01/07 6 MJK0165 0.8 95.4 92.2 15/12/87 13/07/10 26/01/04 13/07/10 13/07/10 7 TJK0629 71.9 100 49.2 01/01/02 13/12/06 29/04/08 11/12/11 11/12/11 7 TJK0175 0.9 90.6 22.9 01/09/00 18/05/10 31/01/12 31/01/12 8 TJK0502 43.2 100 18.6 01/01/02 13/04/08 02/11/10 11/02/11 11/02/11 8 TJK0076 7.3 93.5 55.8 01/11/98 17/06/08 17/06/08 17/06/08 9 TJK0609 42.6 100 17.7 01/08/05 10/06/08 27/03/12 28/12/11 9 TJK0768 5.4 95.8 20.7 01/06/07 03/05/11 01/11/11 01/11/11 10 TJK0659 43 100 37.5 04/08/04 03/03/08 18/01/12 18/01/12 10 TJK0832 13.6 95.8 6.8 01/03/05 01/03/11 06/03/12 06/03/12 11 TJK0717 44.7 100 89.5 01/01/06 12/06/07 02/01/08 03/09/09 03/09/09 11 MJK0151 0.7 91.9 61 15/09/98 30/06/10 30/06/10 30/06/10 12 TJK0748 83.4 100 59.3 01/01/07 14/01/08 14/02/12 14/02/12 12 TJK0345 7 96.5 19.4 01/01/97 04/01/11 20/12/11 20/12/11 13 TJK0805 33.7 98.6 6.3 27/06/07 16/11/10 30/11/11 30/11/11 13 KRR0146 0.08 94.58 73.4 01/01/02 02/11/10 23/09/08 02/11/10 14 MJK1039 31.6 100 92.5 15/01/03 22/05/06 22/05/06 22/05/06 14 TJK0476 11.6 93.3 22.1 01/12/03 17/06/08 01/11/11 01/11/11 15 MJK1045 55.8 100 ND 15/06/01 10/05/06 09/05/06 09/05/06 15 TJK0082 6.5 90 44.6 15/09/95 22/02/11 06/03/12 06/03/12 16 MJK1258 27.4 100 281.1 07/12/05 25/06/07 25/06/07 25/06/07 16 TJK0160 1 96.2 34.2 01/12/97 01/02/11 15/12/11 15/12/11 17 JGG0033 36.8 99.7 197 15/06/97 23/01/01 22/01/01 22/01/01 17 TJK0705 1 98 31.2 01/01/00 13/04/10 29/07/11 22/11/11 18 MJK0215 34.8 99.7 56.9 15/01/98 01/07/02 27/02/02 27/02/02 18 TJK0640 8.7 93.9 29.8 01/11/01 01/11/10 01/11/10 01/11/10 19 MJK0458 44.7 99.7 18 26/11/01 10/07/06 11/07/05 11/07/05 19 TJK0639 8.2 95.5 35.8 01/01/06 30/11/10 24/01/12 24/01/12 20 MJK0840 24.1 99.7 51.9 19/03/96 14/09/05 13/09/05 10/10/06 10/10/06 20 TJK0728 0.5 94.6 133 01/01/98 09/03/10 31/01/12 31/01/12 21 JCB0141 0.13 89.5 24.8 20/06/99 31/01/97 04/05/09 11/04/11 21 JCB0124 0.2 93.8 34.6 18/05/02 19/07/06 25/08/03 19/07/06 19/07/06 22 JCB0246 26.7 100 39.2 01/01/95 01/01/95 21/09/04 29/11/04 29/11/04 22 JGG0015 0.5 93.1 50.1 01/07/99 31/01/11 28/07/11 22/09/11 23 JCB0266 86.1 100 90.8 01/04/98 31/03/09 31/03/09 17/08/09 17/08/09 23 JGG0211 0.4 93 83.5 18/03/02 25/06/02 24/06/02 25/06/02 24 JRB0044 99 100 77.3 01/02/05 15/10/07 04/10/11 04/10/11 24 KRR0183 0.2 95.8 85 NA 15/10/03 10/07/03 14/07/03 25 KRR0461 64.3 100 123.8 01/01/00 15/09/10 15/09/10 15/09/10 25 KRR0295 0.4 97.5 49.8 01/07/99 29/04/11 28/07/10 29/04/11 26 KRR0487 51 100 173.6 01/01/98 29/03/06 29/03/06 29/03/06 26 KRR0322 0.4 95.5 128.5 01/09/98 11/06/08 11/06/08 11/06/08 27 KRR0730 95.2 100 106.3 01/01/04 28/01/08 03/01/08 03/01/08 27 KRR0330 0.4 92 47.4 01/04/04 03/03/11 03/03/11 03/03/11 28 KRR0743 49.9 ND 136 01/04/03 15/02/09 19/02/08 19/02/08 28 KRR0736 0.31 93.1 65.1 01/05/04 29/01/08 29/01/08 29/01/08 29 KRR0755 97.6 97.1 217.7 01/03/06 22/04/08 22/04/08 02/08/11 29 KRR0874 0.36 94 636 01/07/03 16/04/09 16/04/09 16/04/09 30 MJK0808 3.2 100 88.4 01/07/99 06/07/05 05/07/05 22/10/05 22/10/05 30 MJK0005 0.8 96.2 124.7 30/06/94 06/10/00 05/10/00 05/10/00 31 MJK0855 12.4 100 202.7 15/03/04 20/10/05 12/10/05 06/07/06 06/07/06 31 MJK0134 0.2 90 133.7 19/04/97 10/04/01 10/04/01 10/04/01 32 MJK1003 80.2 100 116.2 15/11/01 17/04/06 23/03/06 06/07/07 06/07/07 32 MJK0888 6 88.9 30.2 20/01/05 15/11/05 21/11/05 22/11/05 33 MJK1087 68.9 100 85.1 15/10/02 18/07/06 17/07/06 16/10/06 33 MJK0940 LA 2.1 69.1 64.6 15/06/97 30/01/06 30/01/06 30/01/06 34 NEK0215 97.1 99 116.9 14/08/01 20/09/01 15/02/06 29/02/08 29/02/08 34 MJK1017 1.9 88.5 56.6 24/10/00 04/05/06 11/04/06 11/04/06 35 TJK0553 28.5 100 21.4 01/12/03 01/01/07 29/12/08 29/03/09 29/03/09 35 TJK0025 1.1 93.3 15.7 01/05/97 07/09/05 14/12/11 14/12/11 36 TJK0658 82.7 100 59.9 01/09/03 01/01/04 02/05/06 02/05/06 36 TJK0085 1.9 88.1 24.5 26/03/97 20/04/99 19/08/99 20/04/99 37 TJK0658 82.7 100 59.9 01/09/03 01/01/04 02/05/06 02/05/06 37 TJK0912 0.24 96.1 34.3 01/01/07 07/07/10 20/03/12 20/03/12 38 TJK0831 84.9 98.6 104.5 01/10/02 01/02/11 07/02/12 07/02/12 38 TJK0975 0.36 90 79.9 01/08/07 03/08/10 17/05/11 17/05/11 39 TJK0882 11.5 85.6 24.4 01/01/98 01/01/98 15/02/11 15/02/11 39 TJK1152 27 92.5 34 01/10/07 22/03/11 22/03/11 22/03/11 40 WGW0079 31.3 100 ND 15/07/05 23/12/08 07/06/06 23/12/08 23/12/08 40 WGW0035 3 89.1 62.7 15/09/04 19/03/10 24/01/05 24/01/05

Table S2: Predicted mir-125b target transcripts encoding enzymes or factors downregulated in MEC2 cells following mir-125b overexpression Gene symbol Gene name Fold down regulati on P value PCTP Phosphatidyl choline transfer protein 2.60 1e-07 TP53INP1 1 Tumor protein p53 inducible nuclear protein 1 2.88 1e-07 LIPA Lipase A, lysosomal acid, cholesterol Esterase 2.24 1e-07 ACSS1 Acyl-coa synthetase short-chain family member 1 2.01 1e-07 BIN2 Bridging integrator 2 2.41 2e-07 SPARC Secreted protein, acidic, cysteine-rich (osteonectin) 1.90 2e-07 TAF4B TAF4b RNA polymerase II, TATA box binding protein 1.93 3e-07 HTATIP2 HIV-1 Tat interactive protein 2, 30kda 1.99 4e-07 FUT7 Fucosyltransferase 7 (alpha (1,3) fucosyltransferase) 5.00 4e-07 FAM102A Family with sequence similarity 102, Member A 1.76 4e-07 DUS1L Dihydrouridine synthase 1-like (S. Cerevisiae) 1.79 4e-07 KLF13 Kruppel-like factor 13 1.77 5e-07 STARD13 Star-related lipid transfer (START) domain containing 1.74 5e-07 13 SYTL1 Synaptotagmin-like 1 1.81 6e-07 KLHL24 Kelch-like 24 2.30 7e-07 PPP2R1B Protein phosphatase 2 (formerly 2A), regulatory 1.95 7e-07 subunit A, beta isoform CMTM3 CKLF-like MARVEL transmembrane, domain 1.70 8e-07 containing 3 GNPDA1 Glucosamine-6-phosphate deaminase 1 1.77 1e-06 GPR160 G protein-coupled receptor 160 2.42 1e-06 IRAK1 Interleukin-1 receptor-associated kinase 1 1.75 1.4e-06 TMEM50A Transmembrane protein 50A 1.81 1.4e-06 GPR109B G protein-coupled receptor 109B 1.65 1.4e-06 FGFR1 Fibroblast growth factor receptor 1 1.65 1.6e-06 VDR 2,3 Vitamin D (1,25- dihydroxy vitamin D3) receptor 1.58 1.8e-06 NEU1 Sialidase 1 (lysosomal sialidase) 1.65 2.9e-06 TMEM19 Transmembrane protein 19 1.71 3e-06 TMEM77 Transmembrane protein 77 1.55 3.1e-06 ARHGAP26 Rho gtpase activating protein 26 1.95 1.9e-06 RHOQ Ras homolog gene family, member Q 1.70 3.7e-06 CRTAP Cartilage associated protein 1.57 3.7e-06 ADPRH ADP-ribosylarginine hydrolase 1.70 4e-06 ATP5G2 ATP synthase, H+ transporting, mitochondrial F0 1.53 4.1e-06 complex, subunit C2 RAB37 RAB37, member RAS oncogene family 1.68 6.1e-06 LBH Limb bud and heart development homolog 1.49 6.3e-06 GORASP1 Golgi reassembly stacking protein 1 1.58 6.3e-06 ABHD3 Abhydrolase domain containing 3 1.62 6.6e-06 NLRC5 NLR family, CARD domain containing 5 1.49 8.6e-06 BMF Bcl2 modifying factor 1.61 1.01e-05 DPH2 DPH2 homolog (S. Cerevisiae) 1.56 1.04e-05 PPP1R16B Protein phosphatase 1, regulatory subunit 16B 1.55 1.09e-05 LANCL1 Lanc lantibiotic synthetase component C-like 1 1.55 1.11e-05 LIPH Lipase, member H 1.70 1.15e-05 PAN2 PAN2 polya specific ribonuclease 1.47 1.18e-05 CCR7 Chemokine (C-C motif) receptor 7 1.52 1.19e-05 ABCB9 ATP-binding cassette, sub-family B, member 9 1.89 1.19e-05 COL4A3 Collagen, type IV, alpha 3 1.54 1.2e-05 ROD1 ROD1 regulator of differentiation 1 1.45 1.22e-05 TMEM101 Transmembrane protein 101 1.47 1.37e-05

ETS1 V-ets erythroblastosis virus E26 oncogene homolog 1 1.47 1.51e-05 B3GALTL Beta 1,3 galactosyltransferase-like 1.62 1.88e-05 ENTPD4 Ectonucleoside triphosphate diphosphohydrolase 4 1.53 1.92e-05 DPYSL3 Dihydropyrimidinase-related protein 3 1.72 2.16e-05 AGXT2L2 Alanine-glyoxylate aminotransferase 2-like 2 1.55 2.25e-05 PDGFD Platelet derived growth factor D 1.70 2.3e-05 CTDSP2 Carboxy-terminal domain, RNA polymerase II, 1.42 2.37e-05 polypeptide A, small phosphatase 2 ARID3A AT rich interactive domain 3A 1.55 2.87e-05 UBE2J1 Ubiquitin-conjugating enzyme E2, J1 1.41 2.92e-05 NAIP NLR family, apoptosis inhibitory protein 1.56 2.93e-05 PAPLN Papilin 1.54 3.26e-05 BAZ2A Bromodomain adjacent to zinc finger domain, 2A 1.43 3.33e-05 RAB3D RAB3D, member RAS oncogene family 1.71 3.38e-05 SESN2 Sestrin-2 1.41 3.39e-05 NLRP1 NLR family, pyrin domain containing 1 1.46 3.46e-05 FOXN3 Forkhead box N3 1.44 3.49e-05 MXD4 MAX dimerization protein 4 1.79 4.3e-05 TP53 4 Tumor protein p53 1.43 4.32e-05 ZFYVE1 Zinc finger, FYVE domain containing 1 1.39 1.394890 GIMAP6 Gtpase, IMAP family member 6 1.43 4.42e-05 ARHGAP25 Rho gtpase activating protein 25 1.49 4.55e-05 P2RX4 Purinergic receptor P2X, ligand-gated ion channel, 4 1.37 4.63e-05 SNX1 Sorting nexin 1 1.42 4.65e-05 FMNL3 Formin-like 3 1.38 4.75e-05 NT5DC1 5 nucleotidase domain containing 1 1.70 4.77e-05 RNF44 Ring finger protein 44 1.37 4.78e-05 ATG4D Autophagy related 4 homolog D, Cysteine protease 1.46 4.88e-05 ATG4D IER3IP1 Immediate early response 3 interacting protein 1 1.48 4.88e-05 STK11IP Serine/threonine kinase 11 interacting protein 1.43 4.89e-05 MTP18 Mitochondrial protein 18 kda 1.58 5.07e-05 UNC84A Unc-84 homolog A (C. Elegans) 1.42 5.17e-05 CORO2A Coronin, actin binding protein, 2A 1.39 5.35e-05 LACTB Lactamase, beta 1.48 5.66e-05 HDAC5 Histone deacetylase 5 1.39 5.67e-05 MTUS1 Mitochondrial tumor suppressor 1 1.56 5.84e-05 PRDM1 3 PR domain containing 1, (BLIMP1) 1.60 5.95e-05 SLC9A8 Solute carrier family 9 (sodium/hydrogen exchanger) 1.39 6.22e-05 PCDHGC3 Protocadherin gamma subfamily C, 3 1.46 6.36e-05 E2F2 E2F transcription factor 2 1.50 6.54e-05 VISA Virus-induced signaling adapter 1.41 6.65e-05 TRAM2 Translocation associated membrane protein 2 1.40 6.7e-05 PSAP Prosaposin, Saposin B (Co-beta-glucosidase) 1.38 6.81e-05 ZBED1 Zinc finger, BED-type containing 1 1.47 7.09e-05 TTC30B Tetratricopeptide repeat domain 30B 1.52 7.15e-05 LYPLA2 Lysophospholipase II 1.40 7.57e-05 SEMA4D Sema domain, immunoglobulin domain (Ig), 1.36 7.73e-05 transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D EMID1 Emilin and multimerin domain-containing protein 1 1.45 7.9e-05 TNRC6B Trinucleotide repeat containing 6B 1.44 7.98e-05 MKNK1 MAP kinase interacting, serine/threonine kinase 1 1.58 8.09e-05 SCARB2 Scavenger receptor class B 1.55 8.1e-05 TAF9B TAF9B RNA polymerase II, TATA box binding 1.60 8.34e-05 protein (TBP)-associated factor, 31kda DAZAP2 DAZ associated protein 2 1.36 8.98e-05 FMR1 Fragile X mental retardation 1 1.34 9.75e-05 TUFT1 Tuftelin 1 1.59 9.89e-05 ZNF281 Zinc finger protein 281 1.44 0.000103 PPP2R5C Protein phosphatase 2, regulatory subunit gamma 1.37 0.000105 ASXL1 Additional sex combs like 1 1.43 0.000105

ERMAP Erythroblast membrane-associated protein 1.41 0.000106 SLC38A9 Solute carrier family 38, member 9 1.46 0.000113 PCSK7 Proprotein convertase subtilisin/kexin type 7 1.40 0.000115 RBM38 RNA binding motif protein 38 1.42 0.000115 INSR Insulin receptor 1.37 0.000115 TSC22D3 TSC22 domain family, member 3 glucocorticoidinduced 1.40 0.000116 leucine zipper (GILZ) TNFSF4 Tumor necrosis factor (ligand) superfamily, member 4 1.58 0.000122 TACSTD2 Tumor-associated calcium signal transducer 2 1.36 0.000126 SEPT6 Septin 6 1.36 0.000126 FLVCR2 Feline leukemia virus subgroup C cellular receptor 1.52 0.000129 family, 2 VPS4B Vacuolar protein sorting-associating protein 4B 1.43 0.000131 (Suppressor of K(+) transport growth defect 1) EXOC7 Exocyst complex component 7 1.37 0.000132 TBRG1 Transforming growth factor beta regulator 1 1.37 0.000133 NPL N-acetylneuraminate pyruvate lyase 1.68 0.000136 KLHL6 Kelch-like 6 (Drosophila) 1.50 0.000137 AKAP13 A kinase (PRKA) anchor protein 13 1.35 0.000140 PGPEP1 Pyroglutamyl-peptidase I 1.41 0.000141 ANTXR2 Anthrax toxin receptor 2 1.33 0.000146 NAPB N-ethylmaleimide-sensitive factor, attachment protein, 1.35 0.000150 beta CDC2L6 Cell division cycle 2-like 6 (CDK8- like) 1.35 0.000158 IRF4 5 Interferon regulatory factor 4 1.35 0.000164 SEC31B SEC31 homolog B (S. Cerevisiae) 1.36 0.000167 CDC42SE1 CDC42 small effector 1 1.34 0.000169 SYVN1 Synovial apoptosis inhibitor 1, synoviolin 1.33 0.000169 VANGL1 Vang-like 1 (van gogh, Drosophila) 1.39 0.000171 PSMD9 Proteasome (prosome, macropain) 26S, subunit, nonatpase, 1.39 0.000174 9 BAK1 BCL2-antagonist/killer 1 1.35 0.000182 FNBP1 Formin binding protein 1 1.34 0.000183 ATP8B2 Atpase, class I, type 8B, member 2 1.33 0.000184 METTL9 Methyltransferase like 9 1.42 0.000186 SLC26A6 Solute carrier family 26, member 6 1.35 0.000191 HHAT Hedgehog acyltransferase 1.47 0.000199 CLN6 Ceroid-lipofuscinosis, neuronal 6, 1.41 0.000202 MAN1B1 Mannosidase, alpha, class 1B, member 1 1.30 0.000205 RABEP2 Rabaptin, RAB gtpase binding effector protein 2 1.38 0.000207 RPL28 Ribosomal protein L28 1.31 0.000208 LNPEP Leucyl/cystinyl aminopeptidase 1.37 0.000218 CYFIP2 Cytoplasmic FMR1 interacting protein 2 1.32 0.000219 AMT Aminomethyltransferase 1.39 0.000230 ATP10D Atpase, class V, type 10D 1.40 0.000231 SMEK1 SMEK homolog 1, suppressor of mek1 1.40 0.000231 RAF1 V-raf-1 murine leukemia viral 1.34 0.000232 GSS Glutathione synthetase 1.37 0.000234 BDH1 3-hydroxybutyrate dehydrogenase, type 1 1.42 0.000234 WWC3 WWC family member 3 1.30 0.000241 FAM134C Family with sequence similarity 134, member C 1.32 0.000249 CREB3L2 Camp responsive element binding protein 3-like 2 1.32 0.000258 PSMB9 Proteasome (prosome, macropain) subunit, beta type, 9 1.33 0.000260 (large multifunctional peptidase 2) ZNF10 Zinc finger protein 10 1.34 0.000271 KLHL14 Kelch-like 14 (Drosophila) 1.50 0.000276 CCDC21 Coiled-coil domain containing 21 1.30 0.000282 RFX5 Regulatory factor X, 5 1.30 0.000291 ARSD Arylsulfatase D 1.35 0.000303 PIK3IP1 Phosphoinositide-3-kinase interacting protein 1 1.33 0.000322 MCL1 Myeloid cell leukemia sequence 1 1.30 0.000326 M6PR Mannose-6-phosphate receptor (cation dependent) 1.29 0.000339

CPSF6 Cleavage and polyadenylation specific factor 6, 1.29 0.000345 TMEM198 Transmembrane protein 198 1.32 0.000347 SEMA4B Sema domain 4B 1.31 0.00037 PDXDC1 Pyridoxal-dependent decarboxylase domain containing 1.40 0.000386 1 IKZF2 IKAROS family zinc finger 2 (Helios) 1.32 0.000386 NT5E 5'-nucleotidase, ecto (CD73) 1.30 0.000387 MAP3K1 Mitogen-activated protein kinase kinase kinase 1 1.33 0.00039 C9orf86 Chromosome 9 open reading frame 86 1.39 0.000400 ARHGEF2 Rho/rac guanine nucleotide exchange factor (GEF) 2 1.37 0.000406 CARS2 Cysteinyl-trna synthetase 2, mitochondrial 1.35 0.000427 BAGE2 B melanoma antigen family, member 2 1.31 0.000430 TAZ Tafazzin ( Lysophospholipid acyltransferases) 1.37 0.000432 ZNF697 Zinc finger protein 697 1.46 0.000432 ITCH Itchy E3 ubiquitin protein ligase homolog (mouse) 1.33 0.000436 ABTB1 Ankyrin repeat and BTB (POZ) domain containing 1 1.45 0.000438 ERMP1 Endoplasmic reticulum metallopeptidase 1 1.27 0.000449 GOLGB1 Golgin B1, golgi integral membrane protein 1.30 0.000454 C11orf24 Chromosome 11 open reading frame 24 1.29 0.000464 THOC6 THO complex 6 homolog 1.37 0.000466 TXNDC6 Thioredoxin domain containing 6 ( Protein Disulfide 1.50 0.000469 Oxidoreductases) ATP2A3 Atpase, Ca++ transporting, ubiquitous 1.28 0.000482 FRAT2 Frequently rearranged in advanced Tcell lymphomas 2 1.29 0.000484 IGF1R Insulin-like growth factor 1 receptor 1.39 0.000495 IKZF3 IKAROS family zinc finger 3 (Einos) 1.33 0.000386 Validated targets of mir-125: 1. Gururajan, M. et al. MicroRNA-125b inhibition of B cell differentiation in germinal centers. Int. Immunol. 7, 583-592 (2010). 2. Mohri, T., Nakajima, M., Takagi, S., Komagata, S. & Yokoi, T. MicroRNA regulates human vitamin D receptor. Int. J. Cancer 125, 1328-1333 (2009). 3. Zhang, L., Stokes, N., Polak, L. & Fuchs, E. Specific micrornas are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment. Cell Stem Cell 8, 294-308 (2011). 4. Le, M.T. et al. MicroRNA-125b is a novel negative regulator of p53. Genes Dev. 3, 862-876 (2009). 5. Malumbres, R. et al. Differentiation stage-specific expression of micrornas in B lymphocytes and diffuse large B-cell lymphomas. Blood 113, 3754-3764 (2009).

p-value q-value p-value q-value p-value q-value Table S3: Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p 0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. All data normalized using Bradford protein concentration. Fold of Change Welch's Two-Sample t-test Statistical Value Welch's Two-Sample t-test Mean Values PATHWAY SORT SUPER PATHWAY SUB PATHWAY BIOCHEMICAL NAME PLATFORM COMP ID KEGG HMDB IND CTRL AGG CTRL AGG IND IND / CTRL AGG / CTRL AGG / IND CTRL IND AGG Super Pathway Sub Pathway PUBCHEM CAS RI MASS 1 glycine GC/MS 11777 C00037 HMDB00123 1.02 1.13 1.11 0.6174 0.2757 0.5461 0.2250 0.2837 0.7632 0.995720 1.013770 1.122228 Amino acid Glycine, serine and threonine metabolism 5 257 127 750 56-40-6; 1166 101.9 8 serine GC/MS 1648 C00065 HMDB03406 1.02 1.09 1.07 0.5280 0.2461 0.9529 0.3342 0.4788 0.8013 1.013242 1.031200 1.105006 Amino acid Glycine, serine and threonine metabolism 59 516 857 581 56-45-1; 1389.1 204 Glycine, serine and threonine metabolism 10 N-acetylserine LC/MS pos 37076 HMDB02931 1.46 1.31 0.90 0.0740 0.0521 0.0657 0.0452 0.8218 0.9811 0.763475 1.111339 1.003544 Amino acid Glycine, serine and threonine metabolism 65249 97-14-3; 1012 148 17 threonine LC/MS pos 1284 C00188 HMDB00167 1.62 1.33 0.82 0.0427 0.0323 0.5136 0.2150 0.1874 0.6750 0.925775 1.500514 1.228851 Amino acid Glycine, serine and threonine metabolism 69 710 196 288 72-19-5; 713 120.1 24 aspartate GC/MS 15996 C00049 HMDB00191 1.47 1.58 1.08 0.2484 0.1417 0.0121 0.0106 0.2256 0.7100 0.808720 1.185361 1.278713 Amino acid Alanine and aspartate metabolism 5960 56-84-8; 1529.7 232 25 asparagine GC/MS 11398 C00152 HMDB00168 0.74 0.93 1.26 0.2289 0.1327 0.4867 0.2079 0.5834 0.8947 1.489115 1.098021 1.380688 Amino acid Alanine and aspartate metabolism 62 676 992 089 70-47-3; 1651.2 231 26 Alanine and aspartate metabolism beta-alanine GC/MS 55 C00099 HMDB00056 0.97 0.99 1.03 0.5388 0.2480 0.3661 0.1740 0.7530 0.9811 1.076792 1.042479 1.069941 Amino acid Alanine and aspartate metabolism 2 394 755 801 56-41-7;107-95-9; 1451.8 174 27 alanine GC/MS 1126 C00041 HMDB00161 0.94 0.96 1.03 0.4826 0.2389 0.9248 0.3280 0.4352 0.8013 1.058355 0.990402 1.019757 Amino acid Alanine and aspartate metabolism 59 507 311 724 56-41-7; 1147.6 115.9 27.1 N-acetylalanine LC/MS neg 1585 C02847 HMDB00766 1.19 1.42 1.20 0.9078 0.3608 0.1800 0.1024 0.1294 0.6583 0.603267 0.717333 0.859540 Amino acid Alanine and aspartate metabolism 88064 97-69-8; 882 130.1 39 glutamate LC/MS pos 57 C00025 HMDB03339 0.99 0.89 0.90 0.6076 0.2725 0.1305 0.0780 0.2908 0.7632 1.227619 1.215122 1.092178 Amino acid Glutamate metabolism 611 56-86-0; 700 148.1 44 glutamine LC/MS pos 53 C00064 HMDB00641 0.95 0.66 0.69 0.4641 0.2337 0.0032 0.0033 0.0198 0.2523 1.576466 1.490518 1.033114 Amino acid Glutamate metabolism 69 920 865 961 56-85-9; 684 147.2 Glutamate metabolism 45 pyroglutamine* LC/MS pos 32672 1.76 1.41 0.80 0.0029 0.0032 0.0382 0.0284 0.1782 0.6750 0.752904 1.323366 1.062730 Amino acid Glutamate metabolism 134508 764 129.2 46 gamma-aminobutyrate (GABA) GC/MS 1416 C00334 HMDB00112 0.90 0.84 0.93 0.0753 0.0525 0.0455 0.0333 0.8624 0.9811 1.369685 1.227382 1.146390 Amino acid Glutamate metabolism 6 992 099 119 56-12-2; 1539.7 304.1 50 Histidine metabolism histidine LC/MS neg 59 C00135 HMDB00177 1.34 1.24 0.93 0.2278 0.1327 0.2667 0.1358 0.8482 0.9811 0.841427 1.125255 1.044598 Amino acid Histidine metabolism 7 733 651 426 5934-29-2; 757 154.1 69 lysine GC/MS 1301 C00047 HMDB00182 1.12 1.02 0.91 0.6373 0.2805 0.5969 0.2404 0.9918 0.9923 1.068848 1.200185 1.094522 Amino acid Lysine metabolism 5962 56-87-1; 1836.7 317.2 71 Lysine metabolism 2-aminoadipate GC/MS 6146 C00956 HMDB00510 1.00 0.95 0.94 0.9739 0.3757 0.9188 0.3271 0.9369 0.9811 1.059415 1.060333 1.001517 Amino acid Lysine metabolism 469 542-32-5;1118-90-7; 1686.5 260.1 79 N6-acetyllysine LC/MS pos 36752 C02727 HMDB00206 0.52 0.42 0.82 < 0.001 0.0006 < 0.001 0.0000 0.0938 0.6116 2.205470 1.137049 0.934145 Amino acid Lysine metabolism 699 197 892 832 692-04-6; 1134 189.1 83 phenylalanine LC/MS pos 64 C00079 HMDB00159 1.25 1.21 0.97 0.4926 0.2408 0.4018 0.1818 0.9268 0.9811 0.851842 1.069011 1.032718 Amino acid Phenylalanine & tyrosine metabolism 69 256 656 140 63-91-2; 2056 166.1 88 p-cresol sulfate LC/MS neg 36103 C01468 1.35 1.08 0.81 0.0128 0.0119 0.3331 0.1617 0.0148 0.2523 0.896022 1.205984 0.970830 Amino acid Phenylalanine & tyrosine metabolism 4615422 3233-57-7; 2896 187.1 99 Phenylalanine & tyrosine metabolism tyrosine LC/MS pos 1299 C00082 HMDB00158 1.24 1.20 0.96 0.5029 0.2443 0.4045 0.1822 0.9278 0.9811 0.926234 1.152050 1.109738 Amino acid Phenylalanine & tyrosine metabolism 60 576 942 100 60-18-4; 1516 182.1 100 3-(4-hydroxyphenyl)lactate LC/MS neg 32197 C03672 HMDB00755 1.39 1.30 0.94 0.0241 0.0205 0.0714 0.0478 0.5544 0.8698 0.756571 1.048068 0.982037 Amino acid Phenylalanine & tyrosine metabolism 9378 6482-98-0; 1395 181.1 127 phenylacetylglycine LC/MS neg 33945 C05598 HMDB00821 1.25 0.93 0.75 0.3552 0.1912 0.5068 0.2131 0.0758 0.5584 1.072157 1.336714 0.996723 Amino acid Phenylalanine & tyrosine metabolism 68144 500-98-1; 2377 192.1 144 kynurenine LC/MS pos 15140 C00328 HMDB00684 0.74 0.78 1.06 0.0097 0.0093 0.1033 0.0650 0.1451 0.6626 1.288160 0.948182 1.006407 Amino acid Tryptophan metabolism 1 611 666 971 029 2922-83-0; 1902 209.1 145 tryptophan LC/MS pos 54 C00078 HMDB00929 1.22 1.20 0.98 0.5927 0.2670 0.3944 0.1811 0.7965 0.9811 0.874708 1.062897 1.045590 Amino acid Tryptophan metabolism 69 235 166 305 73-22-3; 2445 205.1 151 Tryptophan metabolism tryptophan betaine LC/MS pos 37097 C09213 0.60 0.77 1.29 0.0416 0.0317 0.2577 0.1339 0.2578 0.7547 1.262669 0.757931 0.977631 Amino acid Tryptophan metabolism 442106 20671-76-5; 2464 247.1 161 serotonin (5HT) LC/MS pos 2342 C00780 HMDB00259 1.30 0.96 0.74 0.1390 0.0868 0.3913 0.1805 0.0226 0.2568 1.005602 1.302952 0.961129 Amino acid Tryptophan metabolism 5202 153-98-0; 1660 177.1 164 C-glycosyltryptophan* LC/MS pos 32675 1.08 0.98 0.90 0.9306 0.3657 0.7534 0.2876 0.6644 0.9364 1.071930 1.162198 1.050684 Amino acid Tryptophan metabolism 1912 367.1 173 3-methyl-2-oxovalerate LC/MS neg 15676 C00671 HMDB03736 2.32 2.54 1.09 0.1457 0.0894 0.0083 0.0076 0.2599 0.7547 0.217436 0.505480 0.551659 Amino acid Valine, leucine and isoleucine metabolism 47 51829-07-3; 2106 129.2 178 beta-hydroxyisovalerate LC/MS neg 12129 HMDB00754 2.52 2.29 0.91 < 0.001 0.0000 < 0.001 0.0000 0.8638 0.9811 0.475482 1.197999 1.090492 Amino acid Valine, leucine and isoleucine metabolism 69362 625-08-1; 1043 117.1 180 isoleucine LC/MS pos 1125 C00407 HMDB00172 1.22 1.23 1.01 0.8306 0.3392 0.5032 0.2126 0.6972 0.9376 0.848664 1.038713 1.047898 Amino acid Valine, leucine and isoleucine metabolism 791 73-32-5; 1614 132.1 181 leucine LC/MS pos 60 C00123 HMDB00687 1.13 1.11 0.98 0.8083 0.3366 0.9809 0.3415 0.8022 0.9811 0.874380 0.991443 0.971169 Amino acid Valine, leucine and isoleucine metabolism 70 457 986 106 61-90-5; 1674 132.2 190 valine LC/MS pos 1649 C00183 HMDB00883 1.38 1.29 0.93 0.5222 0.2461 0.4670 0.2008 0.9923 0.9923 0.878386 1.212398 1.131635 Amino acid Valine, leucine and isoleucine metabolism 69 710 186 287 72-18-4; 1040 118.1 Valine, leucine and isoleucine metabolism 193 4-methyl-2-oxopentanoate LC/MS neg 22116 C00233 HMDB00695 1.65 2.30 1.39 0.4199 0.2182 0.0139 0.0119 0.0777 0.5584 0.413426 0.682748 0.950887 Amino acid Valine, leucine and isoleucine metabolism 70 816-66-0; 2200 129.2 200 isobutyrylcarnitine LC/MS pos 33441 1.94 1.76 0.91 < 0.001 0.0002 < 0.001 0.0002 0.7795 0.9811 0.667507 1.296548 1.177587 Amino acid Valine, leucine and isoleucine metabolism 25518-49-4; 1941 232.2 202 Amino acid 2-methylbutyroylcarnitine LC/MS pos 35431 HMDB00378 3.44 2.85 0.83 < 0.001 0.0000 < 0.001 0.0000 0.9729 0.9873 0.482173 1.660091 1.374845 Amino acid Valine, leucine and isoleucine metabolism 6426901 31023-25-3; 2439 246.1 205 isovalerylcarnitine LC/MS pos 34407 HMDB00688 5.20 3.86 0.74 < 0.001 0.0000 < 0.001 0.0000 0.3350 0.7749 0.222137 1.155911 0.856381 Amino acid Valine, leucine and isoleucine metabolism 6426851 2533 246.2 206 hydroxyisovaleroyl carnitine LC/MS pos 35433 1.27 1.21 0.96 0.4283 0.2203 0.3639 0.1738 0.9063 0.9811 0.682363 0.865292 0.827230 Amino acid Valine, leucine and isoleucine metabolism 99159-87-2; 1683 262.1 213 cysteine GC/MS 31453 C00097 HMDB00574 0.41 0.38 0.92 < 0.001 0.0005 < 0.001 0.0001 0.2806 0.7632 2.957109 1.219499 1.125983 Amino acid Cysteine, methionine, SAM, taurine metabolism 58 626 419 722 52-90-4;56-89-3; 1560.1 218 216 S-methylcysteine GC/MS 40262 HMDB02108 0.85 0.81 0.95 0.1066 0.0695 0.0686 0.0466 0.8495 0.9811 1.108233 0.937118 0.894581 Amino acid Cysteine, methionine, SAM, taurine metabolism 705 817 424 417 1187-84-4; 1447.8 162.1 219 methionine sulfoxide LC/MS pos 18374 C02989 HMDB02005 1.59 1.41 0.89 0.5188 0.2461 0.4485 0.1964 0.9595 0.9811 0.674123 1.068798 0.950428 Amino acid Cysteine, methionine, SAM, taurine metabolism 1 589 801 548 907 3226-65-1; 729 166.1 221 hypotaurine GC/MS 590 C00519 HMDB00965 0.68 0.88 1.30 0.0032 0.0035 0.4437 0.1953 0.0070 0.1912 1.479580 1.008011 1.306890 Amino acid Cysteine, methionine, SAM, taurine metabolism 107812 300-84-5; 1598.5 188 222 Cysteine, methionine, SAM, taurine metabolism taurine GC/MS 2125 C00245 HMDB00251 1.60 1.63 1.02 0.8237 0.3376 0.2703 0.1362 0.4213 0.8013 0.862820 1.383438 1.405749 Amino acid Cysteine, methionine, SAM, taurine metabolism 11 234 068 592 107-35-7; 1616.4 254.1 224 S-adenosylhomocysteine (SAH) LC/MS pos 39540 C00021 HMDB00939 1.87 1.82 0.97 < 0.001 0.0002 < 0.001 0.0002 0.9766 0.9875 0.670087 1.254333 1.219448 Amino acid Cysteine, methionine, SAM, taurine metabolism 979-92-0; 1480 193.2 225 methionine LC/MS pos 1302 C00073 HMDB00696 1.14 1.00 0.88 0.7627 0.3241 0.6256 0.2488 0.4452 0.8013 1.013664 1.154399 1.011686 Amino acid Cysteine, methionine, SAM, taurine metabolism 69 920 876 137 63-68-3; 1252 150.1 227 N-acetylmethionine LC/MS neg 1589 C02712 HMDB11745 1.24 1.07 0.86 0.3541 0.1912 0.5491 0.2250 0.6459 0.9329 0.991860 1.227536 1.057639 Amino acid Cysteine, methionine, SAM, taurine metabolism 448580 65-82-7; 1805 190.1 229 2-hydroxybutyrate (AHB) GC/MS 21044 C05984 HMDB00008 1.57 1.64 1.04 0.0631 0.0460 0.0055 0.0054 0.4650 0.8013 0.688392 1.079844 1.126637 Amino acid Cysteine, methionine, SAM, taurine metabolism 440864 3347-90-8; 1169.4 130.9 HMDB01539,H 240 dimethylarginine (SDMA + ADMA) LC/MS pos 36808 C03626 1.43 0.97 0.67 0.0142 0.0131 0.9284 0.3280 0.0010 0.0836 1.015986 1.457542 0.981964 Amino acid Urea cycle; arginine-, proline-, metabolism 123831 812 203.2 MDB03334 241 arginine LC/MS neg 1638 C00062 HMDB00517 1.52 1.44 0.95 0.1547 0.0944 0.0625 0.0437 0.8723 0.9811 0.788102 1.199926 1.137102 Amino acid Urea cycle; arginine-, proline-, metabolism 5 246 487 232 1119-34-2; 728 173.2 244 ornithine GC/MS 1493 C00077 HMDB03374 1.33 1.15 0.87 0.1061 0.0695 0.3243 0.1589 0.3858 0.7920 1.024457 1.366394 1.182993 Amino acid Urea cycle; arginine-, proline-, metabolism 6262 3184-13-2; 1763.8 141.9 245 urea GC/MS 1670 C00086 HMDB00294 1.24 1.08 0.87 0.0756 0.0525 0.2318 0.1266 0.2658 0.7558 0.936487 1.159437 1.014363 Amino acid Urea cycle; arginine-, proline-, metabolism 117 616 150 869 57-13-6; 1223.9 171 246 Urea cycle; arginine-, proline-, metabolism proline LC/MS pos 1898 C00148 HMDB00162 1.31 1.20 0.92 0.0987 0.0652 0.2492 0.1320 0.5690 0.8865 0.836108 1.096771 1.004860 Amino acid Urea cycle; arginine-, proline-, metabolism 1 457 426 971 047 147-85-3; 796 116.1 248 citrulline LC/MS pos 2132 C00327 HMDB00904 0.58 0.37 0.63 < 0.001 0.0010 < 0.001 0.0000 0.0012 0.0836 2.269390 1.324787 0.829109 Amino acid Urea cycle; arginine-, proline-, metabolism 833 372-75-8; 715 176.1 249 N-acetylornithine LC/MS pos 15630 C00437 HMDB03357 1.49 1.29 0.86 0.0014 0.0017 0.0364 0.0275 0.1056 0.6116 0.797603 1.186526 1.025478 Amino acid Urea cycle; arginine-, proline-, metabolism 6 992 102 439 232 6205-08-9; 875 175.2 252 trans-4-hydroxyproline GC/MS 1366 C01157 HMDB00725 1.23 1.13 0.92 0.1197 0.0766 0.2500 0.1320 0.5489 0.8698 0.916858 1.130067 1.038426 Amino acid Urea cycle; arginine-, proline-, metabolism 58 106 971 053 51-35-4; 1537 140 255 argininosuccinate GC/MS 15497 C03406 HMDB00052 1.17 1.42 1.21 0.7775 0.3290 0.3811 0.1793 0.1919 0.6750 0.459884 0.538052 0.653685 Amino acid Urea cycle; arginine-, proline-, metabolism 828 156637-58-0; 2157 446.3 259 creatine LC/MS pos 27718 C00300 HMDB00064 2.20 1.48 0.67 < 0.001 0.0000 0.0021 0.0025 < 0.001 0.0300 0.634150 1.392365 0.938559 Amino acid Creatine metabolism 586 57-00-1; 758 132.1 Creatine metabolism 260 creatinine LC/MS pos 513 C00791 HMDB00562 1.56 1.18 0.75 0.0015 0.0019 0.1116 0.0693 0.0090 0.2165 0.916295 1.433978 1.080169 Amino acid Creatine metabolism 588 60-27-5; 730 114.1 263 Butanoate metabolism 2-aminobutyrate GC/MS 1577 C02261 HMDB00650 1.59 1.49 0.93 0.0015 0.0019 0.0038 0.0040 0.5871 0.8955 0.763950 1.215747 1.135961 Amino acid Butanoate metabolism 4 396 916 971 251 1492-24-6; 1215.7 130 266 5-methylthioadenosine (MTA) LC/MS pos 1419 C00170 HMDB01173 1.72 2.13 1.24 < 0.001 0.0011 < 0.001 0.0000 0.1114 0.6116 0.438898 0.756471 0.936476 Amino acid Polyamine metabolism 439176 2457-80-9; 2427 298.1 270 Polyamine metabolism spermidine LC/MS pos 485 C00315 HMDB01257 4.24 3.78 0.89 < 0.001 0.0000 < 0.001 0.0000 0.9594 0.9811 0.378348 1.605551 1.429320 Amino acid Polyamine metabolism 1102 124-20-9; 533 146.2 273 spermine LC/MS pos 603 C00750 HMDB01256 10.16 6.68 0.66 < 0.001 0.0000 < 0.001 0.0000 0.1323 0.6583 0.188671 1.916333 1.260595 Amino acid Polyamine metabolism 1103 71-44-3; 506 203.2 275 4-guanidinobutanoate LC/MS pos 15681 C01035 HMDB03464 2.48 2.21 0.89 0.0145 0.0132 0.0053 0.0053 0.9269 0.9811 0.403272 0.999927 0.891752 Amino acid Guanidino and acetamido metabolism 500 463-003;463-00-3; 1085 146.1 Guanidino and acetamido metabolism 276 4-acetamidobutanoate LC/MS pos 1558 C02946 HMDB03681 1.81 1.38 0.76 < 0.001 0.0002 0.0077 0.0072 0.0022 0.1211 0.718397 1.299934 0.987960 Amino acid Guanidino and acetamido metabolism 18189 3025-96-5; 1724 146.1 280 glutathione, reduced (GSH) LC/MS pos 2127 C00051 HMDB00125 5.83 5.04 0.86 < 0.001 0.0003 < 0.001 0.0001 0.4578 0.8013 0.334387 1.949575 1.683719 Amino acid Glutathione metabolism 124886 70-18-8; 1274 308.1 282 5-oxoproline LC/MS neg 1494 C01879 HMDB00267 1.82 1.64 0.90 0.0020 0.0023 0.0046 0.0047 0.6731 0.9376 0.654622 1.192593 1.071771 Amino acid Glutathione metabolism 7405 98-79-3; 744 128.2 283 glutathione, oxidized (GSSG) LC/MS pos 27727 C00127 HMDB03337 3.38 4.07 1.20 < 0.001 0.0010 < 0.001 0.0001 0.1659 0.6750 0.444786 1.502970 1.810314 Amino acid Glutathione metabolism 6 535 911 215 652 103239-24-3; 1535 613.1 Glutathione metabolism 284 cysteine-glutathione disulfide LC/MS pos 35159 HMDB00656 0.51 0.53 1.03 0.0154 0.0139 0.0178 0.0145 0.9387 0.9811 1.400659 0.719604 0.744332 Amino acid Glutathione metabolism 4247235 13081-14-6; 821 427.1 285 ophthalmate LC/MS pos 34592 HMDB05765 5.32 4.17 0.78 < 0.001 0.0000 < 0.001 0.0000 0.7624 0.9811 0.210124 1.117286 0.875291 Amino acid Glutathione metabolism 9817431 495-27-2; 1457 290.1 286 S-lactoylglutathione LC/MS neg 15731 C03451 HMDB01066 13.48 16.07 1.19 < 0.001 0.0002 < 0.001 0.0000 0.1016 0.6116 0.118111 1.592475 1.898107 Amino acid Glutathione metabolism 1083 54398-03-7; 1271 378.2 297 glycylglycine GC/MS 21030 C02037 HMDB11733 1.48 1.31 0.89 0.0179 0.0159 0.0579 0.0414 0.4636 0.8013 0.859864 1.274556 1.130126 Peptide Dipeptide 154 889 711 163 556-50-3; 1447.3 258.1 301 glycylleucine LC/MS pos 34398 C02155 HMDB00759 0.38 0.21 0.56 0.0030 0.0033 < 0.001 0.0009 0.6919 0.9376 3.490120 1.327189 0.738526 Peptide Dipeptide 928 431 548 899 869-19-2; 2236 189.1 307 alanylalanine GC/MS 15129 C00993 HMDB03459 0.98 1.13 1.15 0.1449 0.0894 0.8512 0.3159 0.1952 0.6750 0.878305 0.859059 0.989902 Peptide Dipeptide 54 603 626 992 112 1948-31-8; 1379.5 271.1 313 alanylleucine LC/MS pos 37093 0.52 0.18 0.34 < 0.001 0.0002 < 0.001 0.0000 0.1296 0.6583 2.242942 1.175240 0.398133 Peptide Dipeptide 259583 2150 203 317 alanylglutamate LC/MS pos 37064 0.58 0.32 0.55 0.0073 0.0072 < 0.001 0.0011 0.3715 0.7749 1.451186 0.835211 0.457484 Peptide Dipeptide 656476 766 219 327 alpha-glutamylglutamate LC/MS pos 22166 C01425 1.22 0.73 0.60 0.1759 0.1064 0.0136 0.0117 0.4727 0.8013 1.224153 1.487626 0.895417 Peptide Dipeptide 439500 3929-61-1; 857 277.1 333 isoleucylleucine LC/MS pos 36760 1.02 0.77 0.75 0.6634 0.2888 0.6455 0.2514 0.9899 0.9923 0.872798 0.888063 0.668204 Peptide Dipeptide 11644431 26462-22-6; 2856 245.1 339 pro-hydroxy-pro LC/MS pos 35127 HMDB06695 1.48 1.21 0.81 0.0021 0.0024 0.0637 0.0442 0.0191 0.2523 0.854471 1.267675 1.032259 Peptide Dipeptide 11673055 18684-24-7; 960 229.2 342 pyroglutamylglycine LC/MS neg 31522 1.33 1.30 0.98 0.8178 0.3367 0.3988 0.1814 0.5200 0.8450 0.706308 0.939882 0.917089 Peptide Dipeptide 152981 855 185.1 343 pyroglutamylglutamine LC/MS neg 22194 1.15 1.13 0.98 0.8543 0.3449 0.6422 0.2514 0.4737 0.8013 0.771508 0.885586 0.870026 Peptide Dipeptide 109481-23-4; 879 256.1 344 pyroglutamylvaline LC/MS pos 32394 1.16 1.19 1.03 0.9112 0.3608 0.5746 0.2344 0.4654 0.8013 0.787520 0.910444 0.940277 Peptide Dipeptide 152416 2506 229.2 345 valylglutamate LC/MS pos 32454 5.42 2.85 0.53 0.0022 0.0026 0.0021 0.0025 0.7204 0.9501 0.252517 1.368240 0.720863 Peptide Dipeptide 7009623 3062-07-5; 1346 247.1 347 cyclo(phe-pro) LC/MS pos 37095 1.37 1.58 1.15 0.9650 0.3737 0.3064 0.1517 0.3112 0.7749 0.618769 0.850241 0.979271 Peptide Dipeptide 9837725 3651 245.1 349 cyclo(leu-phe) LC/MS pos 37101 0.92 1.05 1.13 0.2744 0.1548 0.9084 0.3246 0.2651 0.7558 0.829123 0.765067 0.866835 Peptide Dipeptide 7076347 4427 261.1 351 cyclo(leu-ala) GC/MS 37082 1.44 1.77 1.23 0.3786 0.2006 0.0192 0.0155 0.1129 0.6116 0.677346 0.976122 1.200805 Peptide Dipeptide 3634567 1803-60-7; 1509 313.1 353 Dipeptide cyclo(leu-pro) LC/MS pos 37104 1.35 1.51 1.12 0.5210 0.2461 0.7453 0.2856 0.3755 0.7767 0.698071 0.940464 1.054575 Peptide Dipeptide 7074739 3445 211.1 354 cyclo(glu-glu) LC/MS pos 37100 1.32 1.26 0.95 0.6388 0.2805 0.3896 0.1805 0.7010 0.9381 0.723322 0.956848 0.909419 Peptide Dipeptide 7408481 1595 259 355 cyclo(gly-phe) GC/MS 37102 1.46 1.25 0.85 0.1265 0.0800 0.1098 0.0686 0.9680 0.9861 0.875571 1.276616 1.090863 Peptide Dipeptide 7076549 1830 257 Peptide 356 valylleucine LC/MS pos 39994 0.74 0.42 0.57 0.0023 0.0026 < 0.001 0.0001 0.3318 0.7749 1.785765 1.323092 0.747705 Peptide Dipeptide 352039 2503.3 231.2 357 cyclo(phe-phe) LC/MS pos 38152 0.60 0.68 1.12 0.0318 0.0253 0.1274 0.0772 0.3616 0.7749 1.272217 0.766360 0.861572 Peptide Dipeptide 2862-51-3; 4527 295.2 360 aspartylleucine LC/MS pos 40068 0.96 0.42 0.44 0.0351 0.0273 < 0.001 0.0001 0.0764 0.5584 1.559779 1.489688 0.655739 Peptide Dipeptide 332962 3062-14-4; 2310 247.2 366 isoleucylglycine LC/MS pos 40008 1.24 0.60 0.49 0.2359 0.1360 0.2340 0.1271 0.9130 0.9811 2.480212 3.070147 1.495295 Peptide Dipeptide 342532 868-28-0; 1732 189.2 369 isoleucylserine LC/MS pos 40012 1.74 0.55 0.32 0.0947 0.0629 0.0067 0.0063 0.4770 0.8013 0.959474 1.669494 0.529055 Peptide Dipeptide 6403-14-1; 1472.5 219.2 373 leucylalanine LC/MS pos 40010 0.76 0.45 0.59 0.0076 0.0074 < 0.001 0.0002 0.1953 0.6750 1.131395 0.859600 0.504911 Peptide Dipeptide 259321 7298-84-2; 1760 203.2 377 leucylglutamate LC/MS pos 40021 2.01 0.73 0.36 0.2581 0.1464 0.0404 0.0298 0.6077 0.9065 1.086490 2.187293 0.791851 Peptide Dipeptide 52 595 895 259 590 1716 261.2 378 leucylglycine LC/MS pos 40045 1.75 0.73 0.42 0.3522 0.1912 0.3333 0.1617 0.9498 0.9811 0.766857 1.345742 0.561678 Peptide Dipeptide 79070 686-50-0; 1800 189.2 388 phenylalanylserine LC/MS pos 40016 1.79 0.54 0.30 0.4887 0.2408 0.1606 0.0931 0.4750 0.8013 0.816233 1.459220 0.439835 Peptide Dipeptide 9859812 16053-39-7; 1808 253.1 389 serylleucine LC/MS pos 40066 0.49 0.26 0.54 0.0081 0.0078 0.0010 0.0013 0.4207 0.8013 3.091153 1.515468 0.814072 Peptide Dipeptide 6665-16-3; 2106 219.2 391 threonylleucine LC/MS pos 40051 0.58 0.40 0.68 < 0.001 0.0010 0.0031 0.0033 0.4571 0.8013 1.583634 0.918092 0.627658 Peptide Dipeptide 4420322 50299-12-2; 2204 233.2 395 tyrosylleucine LC/MS pos 40031 1.84 0.60 0.33 0.7417 0.3190 0.2672 0.1358 0.1094 0.6116 0.354159 0.652882 0.213511 Peptide Dipeptide 870 717 009 561 17355-10-1; 2656 295.2 396 valylisoleucine LC/MS pos 40050 1.23 0.72 0.58 0.1763 0.1064 0.0240 0.0187 0.4065 0.8013 1.030495 1.266240 0.739342 Peptide Dipeptide 52 460 125 246 013 20556-14-3; 2365 231.2 397 Dipeptide derivative carnosine LC/MS neg 1768 C00386 HMDB00033 1.53 1.25 0.82 0.0048 0.0050 0.0684 0.0466 0.1517 0.6678 0.826579 1.266313 1.033792 Peptide Dipeptide derivative 4 392 246 992 100 305-84-0; 813 225.2 404 gamma-glutamylleucine LC/MS pos 18369 HMDB11171 0.83 0.77 0.93 0.0832 0.0571 0.0382 0.0284 0.8120 0.9811 1.143768 0.954110 0.882978 Peptide gamma-glutamyl 151023 2566-39-4; 2744 261.2 405 gamma-glutamylisoleucine* LC/MS pos 34456 HMDB11170 0.86 0.79 0.91 0.0571 0.0419 0.0796 0.0525 0.7566 0.9811 0.844135 0.727181 0.662951 Peptide gamma-glutamyl 2644 261.2 gamma-glutamyl 412 gamma-glutamylphenylalanine LC/MS pos 33422 HMDB00594 1.60 1.83 1.14 0.8480 0.3449 0.1888 0.1050 0.3116 0.7749 0.645717 1.036149 1.183447 Peptide gamma-glutamyl 111299 7432-24-8; 2846 295.1 413 gamma-glutamyltyrosine LC/MS pos 2734 1.56 1.77 1.13 0.8546 0.3449 0.2612 0.1344 0.3474 0.7749 0.581306 0.909253 1.030181 Peptide gamma-glutamyl 94340 7432-23-7; 2073 311.2 453 erythronate* GC/MS 33477 HMDB00613 1.25 1.10 0.88 0.0877 0.0598 0.2572 0.1339 0.3549 0.7749 0.940378 1.174754 1.034343 Carbohydrate Aminosugars metabolism 2781043 13752-84-6; 1546.9 292.1 Aminosugars metabolism 455 N-acetylneuraminate GC/MS 1592 C00270 HMDB00230 1.59 1.37 0.86 0.0040 0.0042 0.0232 0.0182 0.3592 0.7749 0.759983 1.209294 1.040882 Carbohydrate Aminosugars metabolism 131-48-6; 2074.9 245 472 fructose GC/MS 31266 C00095 HMDB00660 0.75 0.61 0.81 0.3308 0.1818 0.0936 0.0605 0.2729 0.7603 1.657150 1.243462 1.012861 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 5984 57-48-7; 1762.7 204 480 6'-sialyllactose GC/MS 39795 G00265 HMDB06569 1.09 1.00 0.92 0.4646 0.2337 0.7206 0.2784 0.5996 0.8994 1.044846 1.138390 1.048394 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 35890-39-2; 2071.5 285.1 482 maltose GC/MS 15806 C00208 HMDB00163 1.56 0.65 0.41 0.9084 0.3608 0.0999 0.0633 0.1053 0.6116 1.003326 1.561333 0.647590 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 439341 6363-53-7; 2142.1 204.1 483 mannitol GC/MS 15335 C00392 HMDB00765 0.80 0.66 0.82 0.1964 0.1171 0.1438 0.0838 0.9231 0.9811 1.538265 1.237368 1.008955 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 6251 69-65-8; 1839 319.1 489 Fructose, mannose, galactose, starch, and sucrose metabolism mannose-6-phosphate GC/MS 1470 C00275 HMDB01078 0.45 0.40 0.88 0.0027 0.0031 0.0050 0.0051 0.4528 0.8013 2.542180 1.154073 1.012848 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 70442-25-0;104872-94-8; 2035.9 387.2 494 stachyose LC/MS neg 15960 C01613 HMDB03553 1.67 1.70 1.02 0.8178 0.3367 0.5219 0.2175 0.6497 0.9335 0.579174 0.965963 0.987355 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 10094-58-3; 932 665.2 495 sorbitol GC/MS 15053 C00794 HMDB00247 0.67 0.55 0.82 0.1422 0.0883 0.0765 0.0509 0.6943 0.9376 2.129220 1.428068 1.167894 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 107428 6706-59-8; 1843 319.1 499 sucrose LC/MS neg 1519 C00089 HMDB00258 1.40 1.42 1.01 0.8182 0.3367 0.5849 0.2376 0.4155 0.8013 0.632231 0.883389 0.894993 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 5988 57-50-1; 875 341.2 506 raffinose LC/MS neg 586 C00492 HMDB03213 1.32 1.33 1.01 0.9640 0.3737 0.5468 0.2250 0.4962 0.8111 0.657977 0.869381 0.875440 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 439242 17629-30-0; 997 503.2 517 glycerate GC/MS 1572 C00258 HMDB00139 1.42 1.19 0.84 0.0891 0.0603 0.6377 0.2514 0.2496 0.7489 0.717167 1.015986 0.853266 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 752 600-19-1; 1360.7 189 Carbohydrate 519 glucose-6-phosphate (G6P) GC/MS 31260 C00668 HMDB01401 0.41 0.38 0.92 0.0041 0.0043 0.0109 0.0099 0.4792 0.8013 2.950075 1.214907 1.115136 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 103192-55-8; 2042.7 387.2 521 glucose GC/MS 20488 C00293 HMDB00122 0.63 0.45 0.72 0.0921 0.0619 0.0016 0.0020 0.0265 0.2787 2.324363 1.459777 1.049892 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 79025 50-99-7; 1866.8 217.1 Glycolysis, gluconeogenesis, pyruvate metabolism 528 2-phosphoglycerate GC/MS 35629 C00631 HMDB03391 8.15 5.31 0.65 < 0.001 0.0002 < 0.001 0.0000 0.9377 0.9811 0.181015 1.474948 0.961816 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 70195-25-4; 1734 459.1 529 3-phosphoglycerate GC/MS 1414 C00597 HMDB00807 6.64 5.15 0.78 < 0.001 0.0000 < 0.001 0.0000 0.7678 0.9811 0.390809 2.593599 2.011211 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 80731-10-8; 1756 299 536 lactate GC/MS 527 C00186 HMDB00190 1.49 1.33 0.89 < 0.001 0.0004 0.0020 0.0024 0.2962 0.7632 0.815814 1.214387 1.086845 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 612 79-33-4; 1102.8 116.9 545 6-phosphogluconate LC/MS neg 15442 C00345 HMDB01316 4.56 1.84 0.40 < 0.001 0.0000 0.0113 0.0100 < 0.001 0.0300 0.632568 2.882796 1.166934 Carbohydrate Nucleotide sugars, pentose metabolism 91493 921-62-0;53411-70-4; 588 275.1 546 arabitol GC/MS 38075 C00474 HMDB01851 0.86 0.74 0.87 0.5311 0.2461 0.2734 0.1364 0.5323 0.8499 1.555088 1.332386 1.156375 Carbohydrate Nucleotide sugars, pentose metabolism 94154 488-82-4; 1687.5 307.1 548 ribitol GC/MS 15772 C00474 HMDB00508 0.98 0.84 0.86 0.7546 0.3232 0.3470 0.1674 0.4468 0.8013 1.275878 1.245622 1.066357 Carbohydrate Nucleotide sugars, pentose metabolism 488-81-3; 1692.4 217 549 Nucleotide sugars, pentose metabolism threitol GC/MS 35854 C16884 HMDB04136 0.91 0.84 0.92 0.0343 0.0269 0.0698 0.0470 0.6326 0.9285 0.985115 0.899461 0.828017 Carbohydrate Nucleotide sugars, pentose metabolism 169019 2418-52-2; 1513 217.1 554 ribose GC/MS 12080 C00121 HMDB00283 0.65 0.57 0.87 0.0278 0.0228 0.0149 0.0125 0.8565 0.9811 1.552643 1.010360 0.883014 Carbohydrate Nucleotide sugars, pentose metabolism 5311110 50-69-1; 1639.2 204 561 Isobar: ribulose 5-phosphate, xylulose 5-phosphate GC/MS 37288 0.74 0.68 0.92 0.0940 0.0628 0.1206 0.0735 0.8714 0.9811 1.654085 1.226988 1.127764 Carbohydrate Nucleotide sugars, pentose metabolism 1935 357.2 565 xylitol GC/MS 4966 C00379 HMDB00568 0.99 0.83 0.84 0.2965 0.1655 0.3541 0.1700 0.8188 0.9811 0.998446 0.988242 0.825328 Carbohydrate Nucleotide sugars, pentose metabolism 6912 87-99-0; 1677.6 307.2 579 citrate GC/MS 1564 C00158 HMDB00094 0.66 0.80 1.21 0.0336 0.0265 0.2460 0.1320 0.2254 0.7100 1.722693 1.144901 1.383527 Energy Krebs cycle 311 77-92-9; 1763.4 273.1 590 succinate GC/MS 1437 C00042 HMDB00254 4.29 5.36 1.25 < 0.001 0.0000 < 0.001 0.0000 0.3680 0.7749 0.335330 1.438778 1.797644 Energy Krebs cycle 1110 110-15-6; 1348 247 Krebs cycle 594 fumarate GC/MS 1643 C00122 HMDB00134 1.93 1.69 0.88 < 0.001 0.0001 < 0.001 0.0000 0.7934 0.9811 0.639131 1.231913 1.082394 Energy Krebs cycle 100-17-8; 1382.1 245 598 Energy malate GC/MS 1303 C00149 HMDB00156 2.32 2.24 0.97 < 0.001 0.0000 < 0.001 0.0000 0.5315 0.8499 0.544643 1.263141 1.219061 Energy Krebs cycle 525 6915-15-7; 1502 233 601 acetylphosphate GC/MS 15488 C00227 HMDB01494 1.32 1.06 0.80 0.1192 0.0766 0.7270 0.2798 0.1501 0.6678 0.957874 1.268862 1.018263 Energy Oxidative phosphorylation 186 94249-01-1; 1263 211 Oxidative phosphorylation

602 phosphate GC/MS 11438 C00009 HMDB01429 1.67 1.45 0.87 < 0.001 0.0001 0.0017 0.0021 0.1770 0.6750 0.733623 1.226776 1.063734 Energy Oxidative phosphorylation 1061 7664-38-2 ; 1307.7 298.9 Energy Oxidative phosphorylation 603 pyrophosphate (PPi) GC/MS 2078 C00013 HMDB00250 1.40 1.20 0.86 0.0544 0.0402 0.2740 0.1364 0.2721 0.7603 0.930768 1.305512 1.119937 Energy Oxidative phosphorylation 644102 1466-09-3; 1642.3 451 604 linoleate (18:2n6) LC/MS neg 1105 C01595 HMDB00673 2.93 2.86 0.98 < 0.001 0.0000 < 0.001 0.0000 0.6841 0.9376 0.436982 1.278671 1.249534 Lipid Essential fatty acid 5280450 60-33-3; 5533 279.3 608 linolenate [alpha or gamma; (18:3n3 or 6)] LC/MS neg 34035 C06427 HMDB01388 4.89 1.95 0.40 < 0.001 0.0003 < 0.001 0.0004 0.3718 0.7749 0.688670 3.366978 1.345187 Lipid Essential fatty acid 5450 277.3 609 dihomo-linolenate (20:3n3 or n6) LC/MS neg 35718 C03242 HMDB02925 2.10 1.74 0.83 < 0.001 0.0003 < 0.001 0.0007 0.4101 0.8013 0.620219 1.305479 1.078372 Lipid Essential fatty acid 5312529 5600 305.4 Essential fatty acid 611 docosapentaenoate (n3 DPA; 22:5n3) LC/MS neg 32504 C16513 HMDB01976 1.20 0.93 0.77 0.2065 0.1217 0.8758 0.3159 0.1100 0.6116 1.102840 1.318062 1.021316 Lipid Essential fatty acid 2234-74-4 ; 5574 329.4 612 docosapentaenoate (n6 DPA; 22:5n6) LC/MS neg 37478 C06429 HMDB13123 1.25 0.97 0.78 0.4718 0.2358 0.8775 0.3159 0.3216 0.7749 1.078855 1.348616 1.046071 Lipid Essential fatty acid 6441454 25182-74-5; 5625 329.4 613 docosahexaenoate (DHA; 22:6n3) LC/MS neg 19323 C06429 HMDB02183 1.18 0.91 0.77 0.5232 0.2461 0.8904 0.3194 0.3335 0.7749 1.079210 1.268326 0.979872 Lipid Essential fatty acid 445580 6217-54-5; 5518 327.3 618 caproate (6:0) LC/MS neg 32489 C01585 HMDB00535 2.98 2.69 0.90 < 0.001 0.0000 < 0.001 0.0000 0.8264 0.9811 0.355269 1.058761 0.955140 Lipid Medium chain fatty acid 8892 142-62-1; 2766 115.2 620 caprylate (8:0) LC/MS neg 32492 C06423 HMDB00482 2.08 2.45 1.18 0.1151 0.0746 0.0356 0.0271 0.5283 0.8499 0.669475 1.390143 1.641181 Lipid Medium chain fatty acid 379 124-07-2; 4367 143.2 621 Medium chain fatty acid pelargonate (9:0) LC/MS neg 12035 C01601 HMDB00847 2.19 1.91 0.87 < 0.001 0.0000 < 0.001 0.0000 0.1115 0.6116 0.568428 1.247187 1.087234 Lipid Medium chain fatty acid 5461016 112-05-0; 4847 157.2 622 caprate (10:0) LC/MS neg 1642 C01571 HMDB00511 1.41 1.25 0.88 0.0195 0.0172 0.1164 0.0718 0.2890 0.7632 0.894751 1.265606 1.116211 Lipid Medium chain fatty acid 2969 112-37-8; 5092 171.2 625 laurate (12:0) LC/MS neg 1645 C02679 HMDB00638 1.90 1.51 0.80 < 0.001 0.0000 0.0013 0.0017 0.0197 0.2523 0.710114 1.347695 1.073198 Lipid Medium chain fatty acid 3893 143-07-7; 5288 199.3 630 myristoleate (14:1n5) LC/MS neg 32418 C08322 HMDB02000 1.95 2.66 1.36 < 0.001 0.0010 < 0.001 0.0001 0.2094 0.6992 0.736369 1.434680 1.955643 Lipid Long chain fatty acid 5281119 544-64-9 ; 5338 225.3 631 pentadecanoate (15:0) LC/MS neg 1361 C16537 HMDB00826 1.74 1.28 0.74 < 0.001 0.0009 0.0812 0.0532 0.0166 0.2523 0.774134 1.349873 0.994205 Lipid Long chain fatty acid 13849 1002-84-2; 5522 241.3 632 palmitate (16:0) LC/MS neg 1336 C00249 HMDB00220 1.86 1.48 0.80 < 0.001 0.0000 0.0024 0.0028 0.0173 0.2523 0.701342 1.302804 1.038694 Lipid Long chain fatty acid 985 57-10-3; 5619 255.3 633 palmitoleate (16:1n7) LC/MS neg 33447 C08362 HMDB03229 1.91 1.36 0.71 < 0.001 0.0003 0.0287 0.0222 0.0135 0.2523 0.801456 1.528567 1.088348 Lipid Long chain fatty acid 445638 373-49-9; 5477 253.3 635 margarate (17:0) LC/MS neg 1121 HMDB02259 1.66 1.37 0.83 < 0.001 0.0002 0.0109 0.0099 0.0473 0.4166 0.752387 1.247837 1.031488 Lipid Long chain fatty acid 10465 506-12-7; 5733 269.3 636 10-heptadecenoate (17:1n7) LC/MS neg 33971 1.81 1.51 0.83 < 0.001 0.0002 0.0013 0.0017 0.1949 0.6750 0.673233 1.221453 1.017186 Lipid Long chain fatty acid 5312435 29743-97-3; 5558 267.3 637 stearate (18:0) LC/MS neg 1358 C01530 HMDB00827 1.75 1.29 0.74 < 0.001 0.0001 0.0347 0.0266 0.0032 0.1262 0.823766 1.437903 1.063596 Lipid Long chain fatty acid 5281 57-11-4; 5886 283.4 639 oleate (18:1n9) GC/MS 1359 C00712 HMDB00207 1.77 1.54 0.87 < 0.001 0.0001 < 0.001 0.0004 0.2991 0.7632 0.733996 1.296159 1.127950 Lipid Long chain fatty acid 445639 112-80-1; 1984.4 339.2 641 Long chain fatty acid cis-vaccenate (18:1n7) GC/MS 33970 C08367 1.90 1.46 0.77 < 0.001 0.0001 0.0112 0.0100 0.0224 0.2568 0.705452 1.340941 1.032471 Lipid Long chain fatty acid 5282761 693-72-1; 1987 339.3 647 nonadecanoate (19:0) LC/MS neg 1356 C16535 HMDB00772 1.38 1.03 0.75 0.0120 0.0112 0.8566 0.3159 0.0044 0.1509 0.971362 1.343653 1.004752 Lipid Long chain fatty acid 12591 646-30-0; 6073 297.3 648 10-nonadecenoate (19:1n9) LC/MS neg 33972 1.88 1.69 0.90 < 0.001 0.0002 < 0.001 0.0003 0.6752 0.9376 0.692697 1.300020 1.171038 Lipid Long chain fatty acid 5312513 73033-09-7; 5775 295.4 653 eicosenoate (20:1n9 or 11) LC/MS neg 33587 HMDB02231 2.68 2.30 0.86 < 0.001 0.0000 < 0.001 0.0000 0.6635 0.9364 0.495344 1.325540 1.140724 Lipid Long chain fatty acid 5955 309.4 655 dihomo-linoleate (20:2n6) LC/MS neg 17805 C16525 3.34 3.46 1.04 < 0.001 0.0000 < 0.001 0.0000 0.5516 0.8698 0.364989 1.219136 1.263613 Lipid Long chain fatty acid 6439848 2091-39-6; 5722 307.3 658 mead acid (20:3n9) LC/MS neg 35174 HMDB10378 1.10 0.83 0.75 0.5142 0.2461 0.3847 0.1801 0.0571 0.4723 0.969934 1.068572 0.803027 Lipid Long chain fatty acid 5312531 20590-32-3; 5642 305.4 659 arachidonate (20:4n6) LC/MS neg 1110 C00219 HMDB01043 2.09 1.54 0.74 0.0013 0.0016 0.0016 0.0020 0.3312 0.7749 0.659285 1.374745 1.017825 Lipid Long chain fatty acid 444899 506-32-1; 5525 303.4 663 docosadienoate (22:2n6) LC/MS neg 32415 C16533 1.57 1.73 1.10 0.0307 0.0248 0.0019 0.0023 0.3993 0.8013 0.739039 1.159649 1.276617 Lipid Long chain fatty acid 5282807 7370-49-2 ; 6017 335.4 665 adrenate (22:4n6) LC/MS neg 32980 C16527 HMDB02226 1.53 1.24 0.81 0.0039 0.0042 0.2484 0.1320 0.0362 0.3525 0.837705 1.284383 1.037415 Lipid Long chain fatty acid 5282844 2091-25-0; 5684 331.3 704 2-hydroxystearate LC/MS neg 17945 C03045 1.48 1.02 0.69 0.2079 0.1219 0.8681 0.3159 0.1399 0.6583 1.087833 1.604874 1.107484 Lipid Fatty acid, monohydroxy 69417 629-22-1; 5705 299.4 Fatty acid, monohydroxy 706 2-hydroxypalmitate LC/MS neg 35675 1.56 1.04 0.67 0.0259 0.0214 0.4607 0.2000 0.0360 0.3525 1.045167 1.631888 1.087411 Lipid Fatty acid, monohydroxy 92836 764-67-0; 5508 271.3 714 Fatty acid, dicarboxylate 2-hydroxyglutarate GC/MS 37253 C02630 HMDB00606 0.68 0.89 1.32 < 0.001 0.0008 0.1696 0.0977 0.0165 0.2523 1.251477 0.847334 1.118668 Lipid Fatty acid, dicarboxylate 43 40951-21-1; 1576 247 733 Fatty acid, amide stearamide GC/MS 37487 C13846 1.17 1.19 1.02 0.8766 0.3524 0.1828 0.1028 0.1890 0.6750 0.824469 0.966891 0.982060 Lipid Fatty acid, amide 31292 124-26-5; 2071 131 746 Fatty acid, branched 17-methylstearate LC/MS neg 38296 1.66 1.30 0.78 0.0049 0.0050 0.1185 0.0727 0.0957 0.6116 0.842268 1.400290 1.097436 Lipid Fatty acid, branched 3083779 2724-59-6; 5987 297.4 795 Eicosanoid 12-HETE LC/MS neg 37536 HMDB06111 0.18 0.11 0.62 < 0.001 0.0000 < 0.001 0.0000 0.0236 0.2578 8.017156 1.409954 0.875451 Lipid Eicosanoid 73837-14-6; 5295 319.3 802 Endocannabinoid oleic ethanolamide LC/MS neg 38102 HMBD02088 4.39 5.50 1.25 < 0.001 0.0000 < 0.001 0.0000 0.4375 0.8013 0.230193 1.010638 1.264980 Lipid Endocannabinoid 5283454 11-58-0;111-58-0; 6553 324.5 809 propionylcarnitine LC/MS pos 32452 C03017 HMDB00824 3.68 2.71 0.74 < 0.001 0.0000 < 0.001 0.0000 0.0925 0.6116 0.522677 1.925637 1.416328 Lipid Fatty acid metabolism (also BCAA metabolism) 107738 17298-37-2 ; 1589 218.2 Fatty acid metabolism (also BCAA metabolism) 811 butyrylcarnitine LC/MS pos 32412 2.03 2.64 1.30 0.0249 0.0209 < 0.001 0.0001 0.0511 0.4360 0.674347 1.369126 1.783035 Lipid Fatty acid metabolism (also BCAA metabolism) 213144 25576-40-3; 2007 232.2 819 deoxycarnitine LC/MS pos 36747 C01181 HMDB01161 2.68 2.72 1.02 < 0.001 0.0000 < 0.001 0.0000 0.9167 0.9811 0.563497 1.508158 1.531027 Lipid Carnitine metabolism 725 6249-56-5; 759 146.1 820 carnitine LC/MS pos 15500 3.64 2.64 0.72 < 0.001 0.0000 < 0.001 0.0000 0.3603 0.7749 0.553202 2.013236 1.458658 Lipid Carnitine metabolism 10917 461-05-2; 702 162.2 821 3-dehydrocarnitine* LC/MS pos 32654 C02636 HMDB12154 2.69 2.34 0.87 < 0.001 0.0003 < 0.001 0.0005 0.6390 0.9302 0.525043 1.412570 1.229833 Lipid Carnitine metabolism 6991982 10457-99-5; 1020 160.2 Carnitine metabolism 822 acetylcarnitine LC/MS pos 32198 C02571 HMDB00201 2.30 1.93 0.84 0.0101 0.0095 0.0026 0.0029 0.9309 0.9811 0.818852 1.882544 1.576747 Lipid Carnitine metabolism 7045767 5080-50-2; 1203 204.2 833 palmitoylcarnitine LC/MS pos 22189 0.28 0.37 1.30 0.1319 0.0829 0.3131 0.1542 0.4561 0.8013 1.683510 0.478418 0.620821 Lipid Carnitine metabolism 461 6865-14-1; 5179 400.4 835 oleoylcarnitine LC/MS pos 35160 HMDB05065 0.57 0.93 1.65 0.0794 0.0548 0.4638 0.2004 0.2226 0.7100 1.029129 0.581719 0.957802 Lipid Carnitine metabolism 5202 426.4 837 cholate LC/MS neg 22842 C00695 HMDB00619 1.07 1.18 1.10 0.6816 0.2956 0.8085 0.3037 0.4654 0.8013 0.767253 0.822315 0.907141 Lipid Bile acid metabolism 81-25-4; 5148 407.4 840 glycocholate LC/MS neg 18476 C01921 HMDB00138 1.10 0.95 0.86 0.2850 0.1600 0.8775 0.3159 0.1397 0.6583 1.005769 1.107976 0.956858 Lipid Bile acid metabolism 10140 475-31-0;863-57-0; 5104 464.4 841 Lipid Bile acid metabolism taurocholate LC/MS neg 18497 C05122 HMDB00036 1.07 0.87 0.81 0.3679 0.1960 0.8743 0.3159 0.0832 0.5824 1.055420 1.131400 0.916241 Lipid Bile acid metabolism 145-42-6; 5122 514.3 843 taurochenodeoxycholate LC/MS neg 18494 C05465 HMDB00951 1.11 0.86 0.78 0.4350 0.2227 0.6446 0.2514 0.0713 0.5559 1.112128 1.239307 0.961159 Lipid Bile acid metabolism 387316 6009-98-9; 5218 498.3 851 glycochenodeoxycholate LC/MS neg 32346 C05466 HMDB00637 1.09 0.90 0.82 0.7824 0.3297 0.5002 0.2123 0.2421 0.7344 1.204065 1.314640 1.078310 Lipid Bile acid metabolism 16564-43-5; 5245 448.4 875 choline phosphate LC/MS pos 34396 4.52 3.82 0.85 < 0.001 0.0000 < 0.001 0.0000 0.9059 0.9811 0.459056 2.074045 1.754709 Lipid Glycerolipid metabolism 135437 72556-74-2; 695 184.1 876 ethanolamine GC/MS 1497 C00189 HMDB00149 1.25 1.30 1.04 0.5323 0.2461 0.1381 0.0815 0.4154 0.8013 0.926616 1.161152 1.205788 Lipid Glycerolipid metabolism 141-43-5; 1304 174.1 877 phosphoethanolamine GC/MS 12102 C00346 HMDB00224 2.20 2.08 0.95 0.0490 0.0365 0.0069 0.0065 0.4853 0.8029 0.870988 1.914071 1.810433 Lipid Glycerolipid metabolism 52 323 241 015 1071-23-4; 1577.3 299.1 880 Glycerolipid metabolism glycerol GC/MS 15122 C00116 HMDB00131 1.25 0.98 0.79 0.0253 0.0211 0.4603 0.2000 0.0095 0.2165 1.036223 1.295997 1.020642 Lipid Glycerolipid metabolism 753 56-81-5; 1311 205 881 choline LC/MS pos 15506 2.10 1.76 0.84 < 0.001 0.0000 < 0.001 0.0001 0.1385 0.6583 0.640266 1.341507 1.126200 Lipid Glycerolipid metabolism 170746 67-48-1; 674 104.2 882 glycerol 3-phosphate (G3P) GC/MS 15365 C00093 HMDB00126 1.61 1.64 1.02 0.0013 0.0017 < 0.001 0.0005 0.6861 0.9376 0.670127 1.075682 1.101465 Lipid Glycerolipid metabolism 754 29849-82-9; 1719.7 357.1 883 glycerophosphorylcholine (GPC) LC/MS pos 15990 C00670 HMDB00086 2.12 1.78 0.84 < 0.001 0.0003 0.0014 0.0018 0.2263 0.7100 0.678742 1.438785 1.210367 Lipid Glycerolipid metabolism 657272 28319-77-9; 694 258.1 890 myo-inositol GC/MS 19934 C00137 HMDB00211 1.62 1.98 1.22 0.0243 0.0206 0.0026 0.0029 0.2963 0.7632 0.790291 1.283604 1.566338 Lipid Inositol metabolism 87-89-8; 1924.9 217 891 chiro-inositol GC/MS 37112 1.23 1.30 1.06 0.9575 0.3735 0.3806 0.1793 0.3381 0.7749 0.757346 0.929635 0.980890 Lipid Inositol metabolism 643-12-9; 1857 318.1 892 pinitol GC/MS 37086 C03844 1.08 1.19 1.10 0.6377 0.2805 0.7968 0.3017 0.3972 0.8013 0.853975 0.920947 1.016688 Lipid Inositol metabolism 10284-63-6; 1773 318.1 Inositol metabolism 893 inositol 1-phosphate (I1P) GC/MS 1481 HMDB00213 1.64 1.68 1.02 0.0239 0.0205 < 0.001 0.0005 0.4257 0.8013 0.626481 1.027929 1.052239 Lipid Inositol metabolism 106032-59-1; 2057.8 318.1 898 scyllo-inositol GC/MS 32379 C06153 HMDB06088 1.45 1.70 1.17 0.1896 0.1137 0.0171 0.0140 0.2008 0.6854 1.101021 1.594559 1.870688 Lipid Inositol metabolism 488-59-5; 1893.8 318.2 myo-inositol pentakisphosphate (1,2,4,5,6 or 902 LC/MS neg 38388 1.44 1.05 0.73 < 0.001 0.0007 0.0950 0.0606 0.0030 0.1262 0.553130 0.793928 0.579522 Lipid Inositol metabolism 533 579 1,3,4,5,6) 909 1-palmitoylglycerophosphoethanolamine LC/MS neg 35631 HMDB11503 1.26 1.17 0.92 0.2435 0.1397 0.4231 0.1888 0.6654 0.9364 0.789320 0.996029 0.920585 Lipid Lysolipid 9547069 5940 452.3 914 1-stearoylglycerophosphoethanolamine LC/MS neg 34416 HMDB11130 1.10 0.93 0.85 0.8816 0.3531 0.3907 0.1805 0.3360 0.7749 1.066313 1.171476 0.993435 Lipid Lysolipid 9547068 69747-55-3; 6200 480.4 915 1-oleoylglycerophosphoethanolamine LC/MS neg 35628 HMDB11506 2.30 1.95 0.85 < 0.001 0.0003 < 0.001 0.0005 0.6594 0.9364 0.588241 1.350081 1.145197 Lipid Lysolipid 9547071 5928 478.3 916 2-oleoylglycerophosphoethanolamine* LC/MS neg 35687 1.69 1.87 1.11 0.0417 0.0317 < 0.001 0.0012 0.2100 0.6992 0.608122 1.025289 1.136990 Lipid Lysolipid 5848 478.3 917 1-linoleoylglycerophosphoethanolamine* LC/MS neg 32635 HMDB11507 1.99 2.01 1.01 0.0059 0.0059 < 0.001 0.0009 0.5954 0.8980 0.543057 1.083007 1.089118 Lipid Lysolipid 5725 476.3 918 2-linoleoylglycerophosphoethanolamine* LC/MS pos 34666 1.06 0.94 0.89 0.5710 0.2594 0.3980 0.1814 0.7911 0.9811 0.850399 0.897780 0.801695 Lipid Lysolipid 5541 478.3 919 1-arachidonoylglycerophosphoethanolamine* LC/MS neg 35186 HMDB11517 1.85 1.74 0.94 < 0.001 0.0005 < 0.001 0.0010 0.6241 0.9210 0.653933 1.208547 1.136095 Lipid Lysolipid 5731 500.3 920 2-arachidonoylglycerophosphoethanolamine* LC/MS pos 34656 2.27 1.71 0.76 0.0211 0.0184 0.1812 0.1025 0.3140 0.7749 0.956455 2.171198 1.639850 Lipid Lysolipid 5525 502.3 922 2-docosapentaenoylglycerophosphoethanolamine* LC/MS pos 34875 0.75 0.61 0.81 0.4197 0.2182 0.4391 0.1943 0.9396 0.9811 1.518163 1.141749 0.928669 Lipid Lysolipid 5548 528.2 923 2-docosahexaenoylglycerophosphoethanolamine* LC/MS pos 34258 1.14 0.78 0.68 0.7588 0.3237 0.8736 0.3159 0.8431 0.9811 1.152303 1.318139 0.897863 Lipid Lysolipid 5512 526.2 Lysolipid 929 1-palmitoylglycerophosphocholine LC/MS pos 33955 1.16 0.88 0.76 0.3931 0.2073 0.7759 0.2950 0.4675 0.8013 1.776239 2.061476 1.566890 Lipid Lysolipid 86554 17364-16-8; 5671 496.4 930 2-palmitoylglycerophosphocholine* LC/MS pos 35253 0.71 1.27 1.78 0.7925 0.3326 0.9321 0.3281 0.8350 0.9811 1.557215 1.108115 1.969890 Lipid Lysolipid 5604 496.3 934 1-stearoylglycerophosphocholine LC/MS pos 33961 0.68 0.61 0.89 0.5264 0.2461 0.4081 0.1830 0.8163 0.9811 1.764798 1.200262 1.069111 Lipid Lysolipid 497299 19420-57-6; 5844 524.4 936 1-oleoylglycerophosphocholine LC/MS pos 33960 0.74 0.78 1.05 0.5552 0.2533 0.5994 0.2404 0.9319 0.9811 1.193421 0.887353 0.928847 Lipid Lysolipid 16081932 19420-56-5; 5700 522.4 937 2-oleoylglycerophosphocholine* LC/MS pos 35254 0.52 0.59 1.14 0.4418 0.2250 0.4877 0.2079 0.9177 0.9811 1.268265 0.656392 0.750054 Lipid Lysolipid 5640 522.4 945 2-arachidonoylglycerophosphocholine* LC/MS pos 35256 0.65 1.01 1.55 0.5273 0.2461 0.6300 0.2495 0.8733 0.9811 1.631047 1.064536 1.651774 Lipid Lysolipid 5524 544.3 954 1-stearoylglycerophosphoinositol LC/MS neg 19324 1.66 1.64 0.99 0.0037 0.0040 < 0.001 0.0005 0.6955 0.9376 0.731448 1.211634 1.199730 Lipid Lysolipid 5800 599.4 959 1-arachidonoylglycerophosphoinositol* LC/MS neg 34214 2.37 1.91 0.80 < 0.001 0.0000 < 0.001 0.0002 0.1937 0.6750 0.580942 1.379013 1.109242 Lipid Lysolipid 5479 619.4 962 1-oleoylglycerophosphoserine LC/MS neg 19260 0.65 0.56 0.87 0.0409 0.0316 0.0160 0.0133 0.7618 0.9811 1.509350 0.976493 0.846354 Lipid Lysolipid 9547099 5690 522.3 964 1-palmitoylplasmenylethanolamine* LC/MS neg 39270 0.75 0.60 0.80 0.0070 0.0069 0.0030 0.0032 0.9596 0.9811 1.498491 1.121767 0.900244 Lipid Lysolipid 6153 436.4 970 1-palmitoylglycerol (1-monopalmitin) GC/MS 21127 2.13 1.76 0.83 < 0.001 0.0001 < 0.001 0.0009 0.2783 0.7632 0.680727 1.448129 1.200785 Lipid Monoacylglycerol 14900 542-44-9; 2119.5 371.3 Monoacylglycerol 972 1-stearoylglycerol (1-monostearin) GC/MS 21188 D01947 1.48 1.24 0.84 0.0055 0.0055 0.0603 0.0427 0.1696 0.6750 0.836673 1.239589 1.037305 Lipid Monoacylglycerol 24699 123-94-4; 2186.6 399.4 992 Neurotransmitter acetylcholine LC/MS pos 18790 C01996 HMDB00895 1.54 3.71 2.41 0.3586 0.1920 0.0026 0.0029 0.0203 0.2523 0.142512 0.219446 0.528277 Lipid Neurotransmitter 187 60-32-1; 866 146.1 995 sphingosine LC/MS pos 17747 C00319 HMDB00252 0.66 0.43 0.66 0.4071 0.2136 0.2564 0.1339 0.7184 0.9501 2.331922 1.543922 1.012095 Lipid Sphingolipid 5353955 123-78-4; 5197 300.2 1004 Sphingolipid palmitoyl sphingomyelin GC/MS 37506 0.57 0.58 1.02 < 0.001 0.0001 < 0.001 0.0000 0.4941 0.8111 1.518027 0.866314 0.882338 Lipid Sphingolipid 9939941 2524 311.3 1005 stearoyl sphingomyelin GC/MS 19503 C00550 HMDB01348 1.22 1.14 0.94 0.9217 0.3636 0.9735 0.3402 0.9023 0.9811 0.957646 1.165124 1.094681 Lipid Sphingolipid 6453725 85187-10-6;85187-10-6 ; 2645 311.3 1018 lathosterol GC/MS 33488 C01189 HMDB01170 0.81 0.60 0.74 0.0458 0.0343 0.0028 0.0030 0.3600 0.7749 1.146953 0.930730 0.691143 Lipid Sterol/Steroid 65728 80-99-9 ; 2337 458.5 1020 cholesterol GC/MS 63 C00187 HMDB00067 1.01 0.88 0.87 0.6320 0.2805 0.1416 0.0831 0.3655 0.7749 1.069767 1.077148 0.939583 Lipid Sterol/Steroid 6432564 57-88-5; 2316.9 329.3 Sterol/Steroid 1023 7-alpha-hydroxycholesterol GC/MS 35692 C03594 HMDB01496 1.41 1.11 0.79 0.6559 0.2868 0.5886 0.2380 0.9582 0.9811 0.582366 0.823228 0.648353 Lipid Sterol/Steroid 107722 566-27-8; 2300 456.2 1024 7-beta-hydroxycholesterol GC/MS 35092 C03594 HMDB06119 1.15 0.80 0.70 0.7194 0.3107 0.1292 0.0777 0.2355 0.7305 1.095027 1.263951 0.881267 Lipid Sterol/Steroid 473141 566-27-8; 2340 456.4 1095 xanthine GC/MS 3147 C00385 HMDB00292 1.54 1.34 0.87 0.0013 0.0016 0.0170 0.0140 0.1693 0.6750 0.791239 1.217051 1.059793 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 1188 69-89-6; 1889.9 353 1098 hypoxanthine LC/MS neg 3127 C00262 HMDB00157 0.88 0.90 1.01 0.0734 0.0520 0.0944 0.0606 0.9307 0.9811 1.239486 1.094342 1.110757 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 790 68-94-0; 1313 135.1 Purine metabolism, (hypo)xanthine/inosine containing 1099 inosine LC/MS neg 1123 1.09 0.88 0.81 0.9826 0.3777 0.1706 0.0977 0.1329 0.6583 1.651607 1.796163 1.450961 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 58-63-9; 1630 267.2 1101 inosine 5'-monophosphate (IMP) LC/MS pos 2133 C00130 HMDB00175 4.32 2.96 0.68 0.0718 0.0513 0.1348 0.0801 0.6812 0.9376 0.270169 1.167709 0.799288 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 7140378 4691-65-0; 1310 349 1105 adenine GC/MS 554 C00147 HMDB00034 2.51 2.37 0.94 < 0.001 0.0000 < 0.001 0.0000 0.8852 0.9811 0.517900 1.302478 1.225959 Nucleotide Purine metabolism, adenine containing 190 73-24-5; 1804.2 264 1106 adenosine LC/MS pos 555 C00212 HMDB00050 3.60 2.66 0.74 < 0.001 0.0000 < 0.001 0.0000 0.0669 0.5373 0.421932 1.519908 1.123046 Nucleotide Purine metabolism, adenine containing 60961 58-61-7; 1650 268.1 1112 adenosine 2'-monophosphate (2'-AMP) LC/MS pos 36815 C00946 HMDB11617 2.58 2.39 0.93 0.0306 0.0248 0.0064 0.0062 0.6236 0.9210 0.371193 0.958355 0.888554 Nucleotide Purine metabolism, adenine containing 130-49-4; 1625 348.1 Purine metabolism, adenine containing 1113 adenosine 3'-monophosphate (3'-AMP) LC/MS pos 35142 C01367 HMDB03540 0.39 0.41 1.04 < 0.001 0.0002 < 0.001 0.0002 0.8417 0.9811 2.385804 0.934240 0.973100 Nucleotide Purine metabolism, adenine containing 15938966 84-21-9; 1451 348.1 1114 adenosine 5'-monophosphate (AMP) LC/MS pos 32342 C00020 HMDB00045 7.10 5.35 0.75 < 0.001 0.0002 0.0018 0.0022 0.3543 0.7749 0.606753 4.310071 3.243802 Nucleotide Purine metabolism, adenine containing 15938965 149022-20-8; 1210 348.1 1116 adenosine 5'-diphosphate (ADP) LC/MS neg 3108 C00008 HMDB01341 1.96 1.62 0.83 0.5262 0.2461 0.6821 0.2646 0.8083 0.9811 0.666793 1.307704 1.079149 Nucleotide Purine metabolism, adenine containing 6022 20398-34-9; 800 426.1 1124 guanine LC/MS pos 32352 C00242 HMDB00132 0.78 0.84 1.08 0.0043 0.0045 0.0121 0.0106 0.9218 0.9811 1.424753 1.106620 1.191528 Nucleotide Purine metabolism, guanine containing 764 73-40-5; 1022 152.1 Nucleotide 1128 Purine metabolism, guanine containing guanosine LC/MS pos 1573 C00387 HMDB00133 0.70 0.54 0.77 0.0657 0.0472 0.0062 0.0060 0.3394 0.7749 2.009604 1.416685 1.084632 Nucleotide Purine metabolism, guanine containing 6802 118-00-3; 1676 284 1131 guanosine 5'- monophosphate (5'-GMP) LC/MS pos 2849 7.01 5.18 0.74 < 0.001 0.0003 0.0037 0.0039 0.3241 0.7749 0.200903 1.407827 1.040611 Nucleotide Purine metabolism, guanine containing 761 5550-12-9; 1300 364 1149 urate GC/MS 1604 C00366 HMDB00289 1.44 1.28 0.89 0.0657 0.0472 0.0473 0.0343 0.9471 0.9811 0.856326 1.229439 1.099003 Nucleotide Purine metabolism, urate metabolism 69-93-2;120K5305; 1928 441.2 Purine metabolism, urate metabolism 1150 allantoin GC/MS 1107 C02350 HMDB00462 1.35 1.06 0.79 0.0317 0.0253 0.2460 0.1320 0.0386 0.3635 0.888786 1.201052 0.945969 Nucleotide Purine metabolism, urate metabolism 204 97-59-6; 1809.8 518.3 1159 Pyrimidine metabolism, cytidine containing cytosine-2',3'-cyclic monophosphate LC/MS neg 37465 C02354 HMDB11691 3.85 2.41 0.63 < 0.001 0.0002 < 0.001 0.0005 0.4172 0.8013 0.489891 1.883946 1.180254 Nucleotide Pyrimidine metabolism, cytidine containing 417654 15718-51-1; 957 304.1 1178 uracil GC/MS 605 C00106 HMDB00300 0.40 0.34 0.85 < 0.001 0.0000 < 0.001 0.0000 0.1456 0.6626 2.659574 1.065149 0.902924 Nucleotide Pyrimidine metabolism, uracil containing 1174 66-22-8; 1370.4 241 1180 uridine LC/MS neg 606 C00299 HMDB00296 2.34 2.19 0.94 < 0.001 0.0001 < 0.001 0.0001 0.7897 0.9811 0.567679 1.331007 1.244708 Nucleotide Pyrimidine metabolism, uracil containing 6029 58-96-8; 1467 243.1 1181 Pyrimidine metabolism, uracil containing pseudouridine LC/MS pos 33442 C02067 HMDB00767 1.59 1.28 0.81 < 0.001 0.0001 0.0140 0.0119 0.0062 0.1892 0.780057 1.239577 0.999432 Nucleotide Pyrimidine metabolism, uracil containing 1445-07-4; 1180 245 1187 uridine monophosphate (5' or 3') LC/MS pos 39879 5.14 4.17 0.81 < 0.001 0.0001 < 0.001 0.0004 0.4814 0.8013 0.201272 1.035442 0.838628 Nucleotide Pyrimidine metabolism, uracil containing 1079 325 1188 uridine-2',3'-cyclic monophosphate LC/MS neg 37137 C02355 HMDB11640 3.68 2.25 0.61 < 0.001 0.0001 < 0.001 0.0005 0.1750 0.6750 0.341973 1.259121 0.770514 Nucleotide Pyrimidine metabolism, uracil containing 4634036 1082 304.9 1193 Purine and pyrimidine metabolism methylphosphate GC/MS 37070 1.19 1.21 1.02 0.4933 0.2408 0.2617 0.1344 0.7116 0.9477 0.901919 1.070008 1.093891 Nucleotide Purine and pyrimidine metabolism 13130 7023-27-0; 1221 240.9 1197 ascorbate (Vitamin C) GC/MS 1640 C00072 HMDB00044 5.02 6.45 1.29 < 0.001 0.0012 < 0.001 0.0001 0.1792 0.6750 0.429827 2.155823 2.774042 Cofactors and vitamins Ascorbate and aldarate metabolism 134-03-2; 1850.1 332.1 1199 threonate GC/MS 27738 C01620 HMDB00943 1.71 1.77 1.04 < 0.001 0.0010 < 0.001 0.0009 0.8962 0.9811 0.732041 1.251556 1.297092 Cofactors and vitamins Ascorbate and aldarate metabolism 151152 70753-61-6; 1560.7 292.1 Ascorbate and aldarate metabolism 1200 glucarate (saccharate) GC/MS 1476 C00818 HMDB00663 1.05 1.22 1.17 0.4744 0.2360 0.8020 0.3025 0.2857 0.7632 0.818663 0.859530 1.002481 Cofactors and vitamins Ascorbate and aldarate metabolism 33037 5793-88-4; 1885.8 333.1 1202 arabonate GC/MS 37516 HMDB00539 1.52 1.59 1.05 0.3294 0.1818 0.1857 0.1038 0.7469 0.9803 0.644754 0.978523 1.022663 Cofactors and vitamins Ascorbate and aldarate metabolism 122045 7643-75-7; 1736 292.1 1221 nicotinamide LC/MS pos 594 C00153 HMDB01406 2.92 3.10 1.06 < 0.001 0.0000 < 0.001 0.0000 0.5926 0.8980 0.456763 1.332941 1.417964 Cofactors and vitamins Nicotinate and nicotinamide metabolism 936 98-92-0; 1267 123.1 1224 Cofactors and vitamins Nicotinate and nicotinamide metabolism nicotinamide adenine dinucleotide (NAD+) LC/MS pos 5278 C00003 HMDB00902 7.08 4.92 0.70 < 0.001 0.0001 < 0.001 0.0000 0.7943 0.9811 0.137018 0.970030 0.674246 Cofactors and vitamins Nicotinate and nicotinamide metabolism ###################### 53-84-9; 1370 664 1242 trigonelline (N'-methylnicotinate) LC/MS pos 32401 HMDB00875 1.75 1.74 0.99 0.5501 0.2521 0.2709 0.1362 0.6405 0.9302 0.648231 1.136004 1.125403 Cofactors and vitamins Nicotinate and nicotinamide metabolism 5570 6138-41-6 ; 757 138.1 1243 Pantothenate and CoA metabolism pantothenate LC/MS pos 1508 C00864 HMDB00210 1.25 1.06 0.85 0.1211 0.0770 0.5443 0.2250 0.1814 0.6750 1.123121 1.399198 1.186342 Cofactors and vitamins Pantothenate and CoA metabolism 6613 137-08-6; 2218 220.1 1259 Riboflavin metabolism flavin adenine dinucleotide (FAD) LC/MS neg 2134 C00016 HMDB01248 1.53 1.26 0.82 0.0015 0.0019 0.0616 0.0433 0.1142 0.6116 0.797167 1.223039 1.006513 Cofactors and vitamins Riboflavin metabolism 643975 146-14-5;84366-81-4; 2413 784.1 1266 Tocopherol metabolism alpha-tocopherol GC/MS 1561 C02477 HMDB01893 0.65 0.64 0.99 < 0.001 0.0005 < 0.001 0.0004 0.8600 0.9811 1.414263 0.913462 0.905860 Cofactors and vitamins Tocopherol metabolism 14985 59-02-9;10191-41-0; 2305.4 502.5 1282 Vitamin B6 metabolism pyridoxate LC/MS neg 31555 C00847 HMDB00017 1.13 0.94 0.83 0.8007 0.3347 0.8159 0.3053 0.5747 0.8865 0.859042 0.968616 0.808157 Cofactors and vitamins Vitamin B6 metabolism 6723 82-82-6 ; 2210 182.1 1288 hippurate LC/MS neg 15753 C01586 HMDB00714 1.33 1.04 0.78 0.0226 0.0196 0.4396 0.1943 0.0166 0.2523 0.889248 1.187059 0.928098 Xenobiotics Benzoate metabolism 464 495-69-2; 2136 178.1 1292 Benzoate metabolism 3-hydroxyhippurate LC/MS neg 39600 HMDB06116 1.58 0.81 0.51 0.4238 0.2191 0.2096 0.1151 0.0424 0.3858 0.515205 0.813713 0.417019 Xenobiotics Benzoate metabolism 450268 1670 194.1 1300 catechol sulfate LC/MS neg 35320 C00090 2.09 1.66 0.80 < 0.001 0.0001 < 0.001 0.0008 0.2166 0.7100 0.409836 0.857526 0.681857 Xenobiotics Benzoate metabolism 3083879 1928 188.9 1318 glycolate (hydroxyacetate) GC/MS 15737 C00160 HMDB00115 1.43 1.29 0.90 0.0158 0.0141 0.0542 0.0390 0.4711 0.8013 0.824996 1.180398 1.062330 Xenobiotics Chemical 3 698 251 757 79-14-1; 1119 177 1347 2-phenoxyethanol GC/MS 27548 1.76 1.41 0.80 0.0017 0.0020 0.0210 0.0168 0.1677 0.6750 0.850003 1.493386 1.197275 Xenobiotics Chemical 122-99-6; 1398.2 151 Chemical 1375 ectoine LC/MS pos 35651 C06231 1.84 1.68 0.91 0.3098 0.1720 0.1952 0.1079 0.8120 0.9811 0.624506 1.148841 1.050642 Xenobiotics Chemical 1 260 416 993 223 96702-03-3; 832 143.1 1376 Xenobiotics phenol red LC/MS neg 36817 C12600 0.96 0.96 1.01 0.3338 0.1824 0.6147 0.2455 0.5724 0.8865 0.872177 0.834059 0.841251 Xenobiotics Chemical 4766 143-74-8; 3650 353.1 1509 daidzein LC/MS neg 32453 C10208 HMDB03312 1.41 1.75 1.24 0.5856 0.2649 0.0865 0.0563 0.2382 0.7305 0.686947 0.968615 1.202338 Xenobiotics Food component/plant 5281708 486-66-8 ; 3541 253.1 1511 genistein LC/MS neg 32448 C06563 HMDB03217 1.51 1.89 1.25 0.2046 0.1213 0.0224 0.0177 0.2542 0.7543 0.574277 0.867752 1.083077 Xenobiotics Food component/plant 5280961 446-72-0 ; 3745 269.1 1565 Food component/plant ergothioneine LC/MS pos 37459 C05570 HMDB03045 0.49 0.50 1.03 < 0.001 0.0010 0.0048 0.0048 0.3429 0.7749 1.805717 0.877967 0.904095 Xenobiotics Food component/plant 3032311 58511-63-0; 847 230.2 1584 stachydrine LC/MS pos 34384 C10172 HMDB04827 1.08 0.88 0.82 0.9507 0.3723 0.8613 0.3159 0.7789 0.9811 1.331287 1.441417 1.177128 Xenobiotics Food component/plant 115244 4136-37-2; 860 144.1 1585 homostachydrine* LC/MS pos 33009 C08283 0.99 0.86 0.87 0.0012 0.0016 0.0012 0.0016 0.8371 0.9811 0.905893 0.895628 0.778853 Xenobiotics Food component/plant 441447 1195-94-4; 1199 158.2 1632 Sugar, sugar substitute, starch erythritol GC/MS 20699 C00503 HMDB02994 1.06 0.89 0.84 0.4654 0.2337 0.8434 0.3144 0.1548 0.6708 1.204834 1.278465 1.075875 Xenobiotics Sugar, sugar substitute, starch 149-32-6; 1517.5 217

Table S4: Genes encoding the human aldehyde dehydrogenases are mostly located in CLL-susceptible loci Gene Name and Function Location Ref. ALDH1A1 aldehyde dehydrogenase 1 family, member A1 9q21.13 retinol metabolism; regulation of the metabolic responses to high-fat diet ALDH1A2 aldehyde dehydrogenase 1 family, member A2 15q21.3 1 catalyzes the synthesis of retinoic acid from retinaldehyde ALDH1A3 aldehyde dehydrogenase 1 family, member A3 15q26.3 uses retinal as a substrate ALDH1B1 aldehyde dehydrogenase 1 family, member B1 9p11.1 unknown ALDH1L1 aldehyde dehydrogenase 1 family, member L1 3q21.3 2 converts 10-formyltetrahydrofolate, NADP, and water to tetrahydrofolate, NADPH, and carbon dioxide ALDH1L2 aldehyde dehydrogenase 1 family, member L2 12q23.3 3 converts 10-formyltetrahydrofolate to tetrahydrofolate and CO2 in an NADP(+)-dependent reaction ALDH2 aldehyde dehydrogenase 2 family 12q24.2 4 alcohol metabolism ALDH3A1 aldehyde dehydrogenase 3 family, member A1 17p11.2 5 oxidizes aromatic and medium-chain saturated and unsaturated aldehyde substrates ALDH3A2 aldehyde dehydrogenase 3 family, member A2 17p11.2 5 catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid ALDH3B1 aldehyde dehydrogenase 3 family, member B1 11q13 6 unknown ALDH3B2 aldehyde dehydrogenase 3 family, member B2 11q13 6 unknown ALDH4A1 aldehyde dehydrogenase 4 family, member A1 1p36 7 proline degradation; converts pyrroline-5-carboxylate to glutamate ALDH5A1 aldehyde dehydrogenase 5 family, member A1 6p22 8 mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase ALDH6A1 aldehyde dehydrogenase 6 family, member A1 14q24.3 9 catalyzes the irreversible oxidative decarboxylation of malonate and methylmalonate semialdehydes to acetyl- and propionyl-coa ALDH7A1 aldehyde dehydrogenase 7 family, member A1 5q31 protects against hyperosmotic stress presumably through the generation of betaine, an important cellular osmolyte, formed from betaine aldehyde. Hyperosmotic stress is coupled to an increase in oxidative stress and lipid peroxidation (LPO) ALDH8A1 aldehyde dehydrogenase 8 family, member A1 6q23.2 10

converts 9-cis-retinal into the retinoid X receptor ligand 9-cisretinoic acid ALDH9A1 aldehyde dehydrogenase 9 family, member A1 1q23.1 11 catalyzes the dehydrogenation of gamma-aminobutyraldehyde to gamma-aminobutyric acid ALDH16A aldehyde dehydrogenase 16 family, member A1 19q13.33 12 1 act on aldehyde substrates and use nicotinamide adenine dinucleotide phosphate (NADP) as a cofactor ALDH18A aldehyde dehydrogenase 18 family, member A1 10q24.3 1 catalyzes the reduction of glutamate to delta1-pyrroline-5- carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine 74% of ALDHs are located in CLL-susceptible loci (shown in bold and underlined) 1. Crowther-Swanepoel, D et al. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nat. Genet. 42, 132-136 (2010). 2. Yağci, M., Sucak, G.T., Oğur, G. & Haznedar, R. Therapy-related refractory anemia with ringed sideroblasts in chronic lymphocytic leukemia. Involvement of 3q21 region. Cancer Genet. Cytogenet. 129, 43-46 (2001). 3. Schmidt, H.H. et al. Deregulation of the carbohydrate (chondroitin 4) sulfotransferase 11 (CHST11) gene in a B-cell chronic lymphocytic leukemia with a t(12;14)(q23;q32). Oncogene 23, 6991-6996 (2004). 4. Ng, D. et al. High-density mapping and follow-up studies on chromosomal regions 1, 3, 6, 12, 13 and 17 in 28 families with chronic lymphocytic leukaemia. Br. J. Haematol. 133, 59-61 (2006). 5. Fink, S.R. et al. Loss of TP53 is due to rearrangements involving chromosome region 17p10 approximately p12 in chronic lymphocytic leukemia. Cancer Genet. Cytogenet. 167, 177-181 (2006). 6. Koduru, P.R., Offit, K. & Filippa, D.A. Molecular analysis of breaks in BCL-1 protooncogene in B-cell lymphomas with abnormalities of 11q13. Oncogene 4, 929-934 (1989). 7. Leupin, N. et al. P73 status in B-cell chronic lymphocytic leukaemia. Leuk. Lymphoma 45, 1205-1207 (2004). 8. Sellick, G.S et al. A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci. Am. J. Hum. Genet. 77, 420-429. (2005). 9. Autio, K. et al. Low number of DNA copy number changes in small lymphocytic lymphoma. Haematologica 83, 690-692 (1998). 10. Amiel, A. et al. Deletion of 6q27 in chronic lymphocytic leukemia and multiple myeloma detected by fluorescence in situ hybridization. Cancer Genet. Cytogenet. 112, 53-56 (1999). 11. Tyybakinoja, A., Vilpo, J. & Knuutila, S. High-resolution oligonucleotide array-cgh pinpoints genes involved in cryptic losses in chronic lymphocytic leukemia. Cytogenet. Genome Res. 118, 8-12 (2007). 12. Crowther-Swanepoel, D. et al. Verification that common variation at 2q37.1, 6p25.3, 11q24.1, 15q23, and 19q13.32 influences chronic lymphocytic leukaemia risk. Br. J. Haematol. 150, 473-479 (2010).

p-value q-value p-value q-value p-value q-value 1 glycine GC/MS 11777 C00037 HMDB00123 0.84 1.15 0.95 0.0739 0.1621 0.2824 0.3883 0.1497 0.3675 1.900607 2.260726 1.068928 0.926310 1.219354 1.288455 100 100 100 100 100 100 Amino acid Glycine, serine and threonine metabolism 5 257 127 750 56-40-6; 1166 101.9 4 N-acetylglycine GC/MS 27710 HMDB00532 0.96 1.02 0.93 0.6785 0.5609 0.9475 0.6906 0.7380 0.5747 1.006930 1.054054 0.918786 0.897789 0.852222 0.919881 50 75 75 100 75 100 Amino acid Glycine, serine and threonine metabolism 10972 543-24-8; 1396.4 143.9 8 serine GC/MS 1648 C00065 HMDB03406 0.91 1.23 1.01 0.2336 0.3202 0.1249 0.3048 0.7371 0.5747 0.990022 1.085644 1.201719 0.974386 1.405451 1.387938 100 100 100 100 100 100 Amino acid Glycine, serine and threonine metabolism 59 516 857 581 56-45-1; 1389.1 204 10 N-acetylserine LC/MS pos 37076 HMDB02931 1.10 1.41 0.96 0.4890 0.4713 0.0251 0.3048 0.6356 0.5478 0.911590 0.827727 1.705521 1.213270 1.001113 1.045098 100 100 100 100 100 100 Amino acid Glycine, serine and threonine metabolism 65249 97-14-3; 1012 148 12 homoserine GC/MS 23642 C00263,C02 926 HMDB00719 1.05 1.26 1.12 0.7263 0.5808 0.2309 0.3704 0.3881 0.4872 0.807131 0.770605 1.043878 0.829395 1.353431 1.206238 100 100 100 100 100 100 Amino acid Glycine, serine and threonine metabolism 126 476 971 022 672-15-1; 1471 218.1 17 threonine LC/MS pos 1284 C00188 HMDB00167 1.33 1.19 0.95 0.0196 0.0819 0.1728 0.3353 0.2891 0.4386 1.212495 0.910050 0.901857 0.756805 0.903388 0.952162 100 100 100 100 100 100 Amino acid Glycine, serine and threonine metabolism 69 710 196 288 72-19-5; 713 120.1 18 N-acetylthreonine LC/MS neg 33939 C01118 1.11 1.14 0.87 0.3908 0.4236 0.3252 0.4211 0.1816 0.3681 0.941761 0.851390 1.130798 0.996130 0.974121 1.115524 100 100 100 100 100 100 Amino acid Glycine, serine and threonine metabolism 4651717 846 160.1 22 betaine LC/MS pos 3141 HMDB00043 1.34 1.17 0.92 0.0042 0.0418 0.2371 0.3704 0.5482 0.5168 1.209284 0.905546 1.550550 1.329878 0.543217 0.588699 100 100 100 100 100 100 Amino acid Glycine, serine and threonine metabolism 247 107-43-7; 721 118.2 24 aspartate GC/MS 15996 C00049 HMDB00191 0.69 1.16 0.96 0.0017 0.0234 0.1710 0.3353 0.3420 0.4653 0.736429 1.062421 2.022186 1.738512 2.605377 2.700466 100 100 100 100 100 100 Amino acid Alanine and aspartate metabolism 5960 56-84-8; 1529.7 232 25 asparagine LC/MS pos 512 C00152 HMDB00168 1.81 1.11 0.98 < 0.001 0.0177 0.4762 0.4987 0.7149 0.5697 1.894304 1.048014 0.949847 0.853445 0.815166 0.831803 100 100 100 100 100 100 Amino acid Alanine and aspartate metabolism 62 676 992 089 70-47-3; 669 133.1 26 beta-alanine GC/MS 55 C00099 HMDB00056 1.03 1.17 0.63 0.7557 0.5872 0.7063 0.6270 0.2953 0.4450 0.932064 0.905689 2.387051 2.044355 1.113423 1.764321 100 100 100 100 100 100 Amino acid Alanine and aspartate metabolism 2 394 755 801 56-41-7;107-95-9; 1451.8 174 27 alanine GC/MS 1126 C00041 HMDB00161 0.92 1.27 0.96 0.2977 0.3679 0.1004 0.3048 0.5096 0.5054 1.563808 1.693143 1.045683 0.822561 2.303542 2.405090 100 100 100 100 100 100 Amino acid Alanine and aspartate metabolism 59 507 311 724 56-41-7; 1147.6 115.9 27.1 N-acetylalanine LC/MS neg 1585 C02847 HMDB00766 0.92 1.10 0.95 0.2962 0.3679 0.3828 0.4531 0.4877 0.5054 0.557979 0.609555 1.072669 0.978167 1.097183 1.159875 100 100 100 100 100 100 Amino acid Alanine and aspartate metabolism 88064 97-69-8; 882 130.1 28 N-carbamoylaspartate GC/MS 1594 C00438 HMDB00828 1.00 1.00 1.24 0.4488 0.5054 0.121276 0.121276 0.121276 0.121276 0.251238 0.203406 0 0 0 0 100 100 Amino acid Alanine and aspartate metabolism 5460257 923-37-5; 1749 257.1 29 N-acetylaspartate (NAA) LC/MS pos 22185 C01042 HMDB00812 1.15 1.30 0.95 0.3389 0.3855 0.0687 0.3048 0.7421 0.5748 24.033060 20.823960 0.463594 0.357382 0.973313 1.028041 100 100 100 100 100 100 Amino acid Alanine and aspartate metabolism 65065 997-55-7;997-55-7 ; 1222 176.1 39 glutamate LC/MS pos 57 C00025 HMDB03339 1.14 1.21 0.92 0.0782 0.1621 0.1510 0.3203 0.2477 0.3999 1.580754 1.387339 1.057887 0.872275 0.816483 0.886080 100 100 100 100 100 100 Amino acid Glutamate metabolism 611 56-86-0; 700 148.1 43 glutamate, gamma-methyl ester LC/MS pos 33487 1.02 1.09 1.33 0.8836 0.6440 0.9283 0.6898 0.2014 0.3876 1.449458 1.426676 0.953009 0.874343 1.000672 0.750229 100 100 100 100 100 100 Amino acid Glutamate metabolism 73913 1499-55-4 ; 1062 162.1 44 glutamine LC/MS pos 53 C00064 HMDB00641 1.43 1.23 0.92 0.0059 0.0538 0.1378 0.3085 0.0870 0.3258 1.748219 1.223448 1.086356 0.881288 0.747188 0.807797 100 100 100 100 100 100 Amino acid Glutamate metabolism 69 920 865 961 56-85-9; 684 147.2 45 pyroglutamine* LC/MS pos 32672 1.69 1.76 0.95 0.0121 0.0704 0.0024 0.1913 0.6585 0.5547 1.328419 0.786286 1.082165 0.615995 0.573388 0.602851 100 100 100 100 100 100 Amino acid Glutamate metabolism 134508 764 129.2 46 gamma-aminobutyrate (GABA) GC/MS 1416 C00334 HMDB00112 1.08 1.28 0.99 0.9546 0.6554 0.5060 0.5211 0.8073 0.5902 1.023461 0.947068 2.407525 1.874241 2.085152 2.102616 100 100 100 100 100 100 Amino acid Glutamate metabolism 6 992 099 119 56-12-2; 1539.7 304.1 48 N-acetyl-aspartyl-glutamate (NAAG) LC/MS pos 35665 C12270 HMDB01067 1.01 1.19 0.83 0.9199 0.6524 0.4757 0.4987 0.1356 0.3533 9.364412 9.278304 0.633397 0.532025 0.956939 1.155686 100 100 75 100 100 100 Amino acid Glutamate metabolism 5255 3106-85-2; 1563 305 50 histidine LC/MS neg 59 C00135 HMDB00177 1.06 1.13 0.99 0.3725 0.4118 0.3349 0.4215 0.9808 0.6353 1.034781 0.976776 1.011583 0.891451 0.772989 0.778152 100 100 100 100 100 100 Amino acid Histidine metabolism 7 733 651 426 5934-29-2; 757 154.1 52 trans-urocanate LC/MS pos 607 C00785 HMDB00301 1.16 1.85 1.33 0.9562 0.6554 0.1175 0.3048 0.4083 0.4896 0.995100 0.859353 0.786708 0.424390 0.542627 0.408328 50 75 75 50 50 75 Amino acid Histidine metabolism 736715 104-98-3; 1119 139.1 63 glutarate (pentanedioate) GC/MS 396 C00489 HMDB00661 0.45 0.88 1.26 0.0069 0.0560 0.8692 0.6727 0.2852 0.4357 0.446522 1.002715 0.678006 0.771220 0.926505 0.734557 75 100 75 75 100 100 Amino acid Lysine metabolism 4418048 110-94-1; 1433.6 261 69 lysine GC/MS 1301 C00047 HMDB00182 0.88 0.60 1.32 0.5713 0.5063 0.4723 0.4987 0.3609 0.4759 1.513382 1.712271 0.470689 0.785040 0.835019 0.634735 100 100 100 100 100 100 Amino acid Lysine metabolism 5962 56-87-1; 1836.7 317.2 71 2-aminoadipate GC/MS 6146 C00956 HMDB00510 0.86 1.08 1.54 0.2308 0.3183 0.7853 0.6554 0.0167 0.2896 2.411014 2.808392 1.083882 1.002373 0.525716 0.341066 100 100 100 100 100 100 Amino acid Lysine metabolism 469 542-32-5;1118-90-7; 1686.5 260.1 79 N6-acetyllysine LC/MS pos 36752 C02727 HMDB00206 1.05 1.33 1.03 0.6852 0.5643 0.0303 0.3048 0.6203 0.5476 0.910972 0.865713 1.332720 1.000102 0.973395 0.945126 100 100 100 100 100 100 Amino acid Lysine metabolism 699 197 892 832 692-04-6; 1134 189.1 83 phenylalanine LC/MS pos 64 C00079 HMDB00159 1.06 1.20 0.99 0.3018 0.3679 0.1333 0.3048 0.9115 0.6156 1.158960 1.089058 1.038813 0.864963 0.947093 0.952334 100 100 100 100 100 100 Amino acid Phenylalanine & tyrosine metabolism 69 256 656 140 63-91-2; 2056 166.1 88 p-cresol sulfate LC/MS neg 36103 C01468 0.86 1.02 1.36 0.4963 0.4728 0.9373 0.6898 0.1214 0.3533 0.714293 0.829846 0.766516 0.749363 1.033815 0.761000 50 75 75 50 100 100 Amino acid Phenylalanine & tyrosine metabolism 4615422 3233-57-7; 2896 187.1 99 tyrosine LC/MS pos 1299 C00082 HMDB00158 1.06 1.28 1.05 0.4136 0.4306 0.0550 0.3048 0.4317 0.5054 1.276572 1.206691 1.228068 0.962746 0.940237 0.898563 100 100 100 100 100 100 Amino acid Phenylalanine & tyrosine metabolism 60 576 942 100 60-18-4; 1516 182.1 100 3-(4-hydroxyphenyl)lactate LC/MS neg 32197 C03672 HMDB00755 0.94 1.24 1.10 0.3067 0.3679 0.0928 0.3048 0.1177 0.3533 0.503473 0.534721 1.352286 1.089001 1.191649 1.082292 100 100 100 100 100 100 Amino acid Phenylalanine & tyrosine metabolism 9378 6482-98-0; 1395 181.1 103 tyramine LC/MS pos 1603 C00483 HMDB00306 1.00 1.00 0.91 0.2320 0.3984 0.851850 0.851850 0.851850 0.851850 0.979590 1.073934 0 0 0 0 100 100 Amino acid Phenylalanine & tyrosine metabolism 5610 60-19-5; 1503 138.1 127 phenylacetylglycine LC/MS neg 33945 C05598 HMDB00821 0.59 1.33 1.38 0.0213 0.0841 0.1100 0.3048 0.0343 0.2896 3.165255 5.401996 1.083418 0.812284 0.428262 0.311250 100 100 100 100 100 100 Amino acid Phenylalanine & tyrosine metabolism 68144 500-98-1; 2377 192.1 144 kynurenine LC/MS pos 15140 C00328 HMDB00684 0.97 1.69 1.08 0.7402 0.5816 0.2708 0.3883 0.7777 0.5822 5.510994 5.675890 1.054098 0.625145 0.845963 0.786523 100 100 100 100 100 100 Amino acid Tryptophan metabolism 1 611 666 971 029 2922-83-0; 1902 209.1 145 tryptophan LC/MS pos 54 C00078 HMDB00929 0.97 1.22 0.98 0.6898 0.5659 0.0980 0.3048 0.8134 0.5908 1.093021 1.122038 1.125645 0.923145 0.966849 0.982750 100 100 100 100 100 100 Amino acid Tryptophan metabolism 69 235 166 305 73-22-3; 2445 205.1 161 serotonin (5HT) LC/MS pos 2342 C00780 HMDB00259 1.26 1.06 1.29 0.5552 0.4984 0.5940 0.5646 0.0333 0.2896 1.893233 1.498132 0.590602 0.558212 0.491792 0.380930 100 100 100 100 100 100 Amino acid Tryptophan metabolism 5202 153-98-0; 1660 177.1 164 C-glycosyltryptophan* LC/MS pos 32675 1.01 1.15 0.91 0.8709 0.6432 0.2590 0.3883 0.5601 0.5213 3.744559 3.714413 0.971141 0.843381 1.068699 1.175229 100 100 100 100 100 100 Amino acid Tryptophan metabolism 1912 367.1 178 beta-hydroxyisovalerate LC/MS neg 12129 HMDB00754 0.82 0.99 1.10 0.2106 0.3057 0.9479 0.6906 0.5380 0.5127 0.770441 0.937225 1.007698 1.021562 0.907233 0.822126 75 100 100 100 100 100 Amino acid Valine, leucine and isoleucine metabolism 69362 625-08-1; 1043 117.1 180 isoleucine LC/MS pos 1125 C00407 HMDB00172 1.02 1.23 1.07 0.6191 0.5215 0.1056 0.3048 0.4169 0.4939 1.122067 1.100735 1.048446 0.855604 0.817926 0.761281 100 100 100 100 100 100 Amino acid Valine, leucine and isoleucine metabolism 791 73-32-5; 1614 132.1 181 leucine LC/MS pos 60 C00123 HMDB00687 1.00 1.18 1.02 0.9152 0.6524 0.1535 0.3203 0.7780 0.5822 1.148348 1.143996 1.105975 0.936957 0.871578 0.853618 100 100 100 100 100 100 Amino acid Valine, leucine and isoleucine metabolism 70 457 986 106 61-90-5; 1674 132.2 186 N-acetylvaline LC/MS pos 1591 HMDB11757 1.43 0.99 0.72 0.2884 0.3674 0.9322 0.6898 0.0560 0.2896 1.108606 0.777955 0.958251 0.964057 0.637130 0.890342 75 50 100 100 100 100 Amino acid Valine, leucine and isoleucine metabolism 66789 96-81-1; 2654 160.1 190 valine LC/MS pos 1649 C00183 HMDB00883 1.07 1.21 1.00 0.2899 0.3674 0.1246 0.3048 0.9055 0.6156 1.284864 1.202451 1.209981 1.003569 0.904120 0.900073 100 100 100 100 100 100 Amino acid Valine, leucine and isoleucine metabolism 69 710 186 287 72-18-4; 1040 118.1 198 alpha-hydroxyisovalerate GC/MS 33937 HMDB00407 1.00 1.07 1.02 0.5944 0.5646 0.9547 0.6281 0.632187 0.632187 1.108245 1.032533 0.836224 0.821844 0 0 100 75 100 75 Amino acid Valine, leucine and isoleucine metabolism 99823 600-37-3; 1208 145.1 200 isobutyrylcarnitine LC/MS pos 33441 1.33 1.63 1.32 0.1402 0.2345 < 0.001 0.1549 0.0295 0.2896 1.085940 0.814862 1.828602 1.123489 0.537722 0.408483 100 100 100 100 100 100 Amino acid Valine, leucine and isoleucine metabolism 25518-49-4; 1941 232.2 202 2-methylbutyroylcarnitine LC/MS pos 35431 HMDB00378 1.20 1.71 0.99 0.1305 0.2250 0.0104 0.3048 0.9601 0.6281 2.089222 1.741992 1.040637 0.609943 0.967302 0.981001 100 100 100 100 100 100 Amino acid Valine, leucine and isoleucine metabolism 6426901 31023-25-3; 2439 246.1 205 isovalerylcarnitine LC/MS pos 34407 HMDB00688 1.25 1.89 1.03 0.2703 0.3509 0.0013 0.1549 0.6865 0.5646 0.599476 0.478897 1.960134 1.036544 0.962567 0.931079 100 100 100 100 100 100 Amino acid Valine, leucine and isoleucine metabolism 6426851 2533 246.2 213 cysteine GC/MS 31453 C00097 HMDB00574 0.39 1.31 1.31 0.0777 0.1621 0.2757 0.3883 0.0654 0.2896 2.826766 7.207850 1.320980 1.009742 5.875732 4.474986 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 58 626 419 722 52-90-4;56-89-3; 1560.1 218 216 S-methylcysteine GC/MS 39592 HMDB02108 0.51 1.42 1.31 0.0505 0.1282 0.1098 0.3048 0.2300 0.3984 0.991504 1.952409 0.879030 0.617014 1.882377 1.436671 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 705 817 424 417 1187-84-4; 1447.8 218.1 217 cystine GC/MS 31454 C00491 HMDB00192 0.23 1.00 1.82 0.0168 0.0798 0.1228 0.3533 0.289265 1.237447 0.133388 0.133388 0.269265 0.147741 50 100 0 0 75 50 Amino acid Cysteine, methionine, SAM, taurine metabolism 595 56-89-3; 2015.3 218 218 cystathionine GC/MS 15705 C02291 HMDB00099 0.87 0.94 1.33 0.4923 0.4724 0.7192 0.6285 0.1300 0.3533 3.909848 4.500054 0.758959 0.803502 1.055353 0.792064 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 4 083 111 834 535-34-2; 1979.6 218.1 220 N-formylmethionine LC/MS neg 2829 C03145 HMDB01015 1.07 1.14 0.97 0.4607 0.4539 0.4317 0.4867 0.9866 0.6353 0.714419 0.666195 1.183647 1.040026 1.082452 1.119879 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 439750 4289-98-9; 1541 176.1 221 hypotaurine LC/MS pos 590 C00519 HMDB00965 1.80 1.15 0.73 0.0044 0.0418 0.4820 0.5008 0.1323 0.3533 0.835888 0.464360 2.131119 1.850104 0.720468 0.985084 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 107812 300-84-5; 674 110.1 222 taurine GC/MS 35961 C00245 HMDB00251 1.09 0.69 1.06 0.7430 0.5816 0.5448 0.5430 0.5974 0.5403 1.463181 1.346257 0.792323 1.156463 0.807177 0.760319 100 100 75 75 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 11 234 068 592 107-35-7; 1652 326.2 224 S-adenosylhomocysteine (SAH) LC/MS neg 15948 C00021 HMDB00939 1.06 1.23 1.13 0.4991 0.4728 0.1038 0.3048 0.0203 0.2896 0.959748 0.907840 1.229125 0.999694 1.071586 0.951353 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 979-92-0; 1821 383.1 225 methionine LC/MS pos 1302 C00073 HMDB00696 1.04 1.24 0.96 0.5392 0.4918 0.1039 0.3048 0.6165 0.5476 1.030997 0.993507 1.033359 0.830964 0.738745 0.771767 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 69 920 876 137 63-68-3; 1252 150.1 227 N-acetylmethionine LC/MS neg 1589 C02712 HMDB11745 1.11 1.27 0.90 0.3596 0.4008 0.0473 0.3048 0.1275 0.3533 0.513494 0.461724 1.440866 1.138102 1.076416 1.199724 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 448580 65-82-7; 1805 190.1 229 2-hydroxybutyrate (AHB) GC/MS 21044 C05984 HMDB00008 1.60 1.62 1.29 0.2657 0.3490 0.0443 0.3048 0.1689 0.3681 1.147983 0.718739 1.282578 0.791029 1.071079 0.828345 75 75 100 75 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 440864 3347-90-8; 1169.4 130.9 231 homocysteine GC/MS 40266 C00155 HMDB00742 0.88 1.07 0.99 0.6083 0.5215 0.8228 0.6659 0.9030 0.6156 4.059745 4.631538 0.978236 0.915725 1.116837 1.130772 100 100 100 100 100 100 Amino acid Cysteine, methionine, SAM, taurine metabolism 778 454-29-5; 1648.2 234 240 dimethylarginine (SDMA + ADMA) LC/MS pos 36808 C03626 HMDB01539,HM DB03334 1.21 1.01 0.76 0.2304 0.3183 0.9766 0.6978 0.0579 0.2896 0.879290 0.728029 0.733787 0.728854 1.050120 1.387124 100 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 123831 812 203.2 241 arginine LC/MS neg 1638 C00062 HMDB00517 1.37 1.05 1.15 0.0320 0.1086 0.6489 0.5960 0.1134 0.3533 1.520658 1.112437 1.051791 0.997609 0.583440 0.506492 100 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 5 246 487 232 1119-34-2; 728 173.2 244 ornithine GC/MS 1493 C00077 HMDB03374 0.88 0.77 1.48 0.5142 0.4791 0.4733 0.4987 0.1953 0.3828 0.769021 0.871788 0.757725 0.979779 0.539923 0.365249 100 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 6262 3184-13-2; 1763.8 141.9 245 urea GC/MS 1670 C00086 HMDB00294 0.84 1.47 0.71 0.7216 0.5808 0.2705 0.3883 0.2406 0.3999 0.786232 0.939929 1.020040 0.693646 0.638645 0.901465 100 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 117 616 150 869 57-13-6; 1223.9 171 246 proline LC/MS pos 1898 C00148 HMDB00162 1.10 1.22 0.98 0.1967 0.2933 0.1349 0.3057 0.9612 0.6281 1.026066 0.929788 1.475811 1.210941 1.420760 1.452804 100 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 1 457 426 971 047 147-85-3; 796 116.1 247 5-aminovalerate LC/MS pos 18319 C00431 HMDB03355 1.06 1.28 1.00 0.8791 0.6440 0.1278 0.3048 0.9107 0.6156 1.336160 1.263172 0.764948 0.599288 1.204268 1.206765 75 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 6 992 101 138 660-88-8; 860 118.1 248 citrulline LC/MS pos 2132 C00327 HMDB00904 1.47 1.31 1.29 0.0733 0.1621 0.1304 0.3048 0.1404 0.3576 0.574615 0.389685 1.087078 0.829792 0.727434 0.565921 100 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 833 372-75-8; 715 176.1 249 N-acetylornithine LC/MS pos 15630 C00437 HMDB03357 1.19 0.98 1.08 0.1474 0.2428 0.9393 0.6898 0.5113 0.5054 1.086206 0.913486 1.019304 1.035422 0.911831 0.840585 100 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 6 992 102 439 232 6205-08-9; 875 175.2 252 trans-4-hydroxyproline GC/MS 1366 C01157 HMDB00725 0.77 1.22 1.04 0.0136 0.0751 0.1271 0.3048 0.4983 0.5054 0.891881 1.164400 1.245021 1.020636 1.149735 1.107706 100 100 100 100 100 100 Amino acid Urea cycle; arginine-, proline-, metabolism 58 106 971 053 51-35-4; 1537 140 255 argininosuccinate GC/MS 15497 C03406 HMDB00052 0.82 0.99 1.18 0.3046 0.3679 0.9733 0.6978 0.5328 0.5127 0.762943 0.930440 0.817829 0.829051 1.394893 1.180370 50 75 50 75 100 75 Amino acid Urea cycle; arginine-, proline-, metabolism 828 156637-58-0; 2157 446.3 259 creatine LC/MS pos 27718 C00300 HMDB00064 0.96 1.28 1.00 0.4725 0.4594 0.1085 0.3048 0.9469 0.6261 8.381348 8.704641 0.533479 0.416842 0.941458 0.944610 100 100 100 100 100 100 Amino acid Creatine metabolism 586 57-00-1; 758 132.1 260 creatinine LC/MS pos 513 C00791 HMDB00562 1.12 1.04 1.18 0.5070 0.4781 0.7910 0.6554 0.1659 0.3681 1.150307 1.028112 0.888963 0.855161 0.635248 0.536124 100 100 100 100 100 100 Amino acid Creatine metabolism 588 60-27-5; 730 114.1 263 Butanoate metabolism 2-aminobutyrate GC/MS 1577 C02261 HMDB00650 0.94 1.24 0.93 0.4487 0.4526 0.1851 0.3468 0.3000 0.4459 1.683043 1.798901 1.102432 0.889945 0.805329 0.864819 100 100 100 100 100 100 Amino acid Butanoate metabolism 4 396 916 971 251 1492-24-6; 1215.7 130 266 5-methylthioadenosine (MTA) LC/MS pos 1419 C00170 HMDB01173 1.34 1.35 1.35 0.0233 0.0873 0.0614 0.3048 0.0070 0.2231 3.768878 2.804704 1.283037 0.948370 0.762955 0.565875 100 100 100 100 100 100 Amino acid Polyamine metabolism 439176 2457-80-9; 2427 298.1 267 putrescine GC/MS 1408 C00134 HMDB01414 1.50 1.26 0.80 0.4459 0.4526 0.1212 0.3048 0.7312 0.5744 1.117160 0.745664 5.297807 4.204424 4.902504 6.129077 100 100 100 100 100 100 Amino acid Polyamine metabolism 110-60-1; 1705.8 174 268 N-acetylputrescine LC/MS pos 37496 C02714 HMDB02064 1.67 1.13 0.84 0.0992 0.1840 0.3368 0.4217 0.1825 0.3681 0.292983 0.175631 1.665928 1.473317 0.957741 1.139154 100 100 100 100 100 100 Amino acid Polyamine metabolism 122356 18233-70-0; 895 131.1 269 agmatine GC/MS 15496 C00179 HMDB01432 0.79 1.25 1.21 0.8063 0.6033 0.1323 0.3048 0.3371 0.4653 0.445557 0.567520 1.073781 0.859470 2.253645 1.866464 100 100 100 100 100 100 Amino acid Polyamine metabolism 199 2482-00-0; 1528 174 270 spermidine LC/MS pos 485 C00315 HMDB01257 1.39 1.33 1.00 0.0218 0.0845 0.0110 0.3048 0.9467 0.6261 2.149012 1.545939 0.654603 0.490367 0.734651 0.734842 100 100 100 100 100 100 Amino acid Polyamine metabolism 1102 124-20-9; 533 146.2 275 4-guanidinobutanoate LC/MS pos 15681 C01035 HMDB03464 1.25 1.27 1.02 0.0298 0.1046 0.1637 0.3329 0.7683 0.5809 1.668748 1.332601 0.588469 0.463517 0.906293 0.888006 100 100 100 100 100 100 Amino acid Guanidino and acetamido metabolism 500 463-003;463-00-3; 1085 146.1 276 4-acetamidobutanoate LC/MS pos 1558 C02946 HMDB03681 1.32 1.07 1.19 0.0868 0.1669 0.5483 0.5430 0.1590 0.3681 1.373279 1.042764 0.884929 0.824806 0.547981 0.460459 100 100 100 100 100 100 Amino acid Guanidino and acetamido metabolism 18189 3025-96-5; 1724 146.1 280 glutathione, reduced (GSH) LC/MS pos 2127 C00051 HMDB00125 2.19 1.28 1.24 0.0022 0.0260 0.1121 0.3048 0.0304 0.2896 1.938225 0.884131 1.586893 1.240139 1.002769 0.809289 100 100 100 100 100 100 Amino acid Glutathione metabolism 124886 70-18-8; 1274 308.1 282 5-oxoproline LC/MS neg 1494 C01879 HMDB00267 0.91 1.15 1.16 0.3038 0.3679 0.2767 0.3883 0.0706 0.3011 1.389820 1.530742 0.911411 0.791476 0.974108 0.840447 100 100 100 100 100 100 Amino acid Glutathione metabolism 7405 98-79-3; 744 128.2 283 glutathione, oxidized (GSSG) LC/MS pos 27727 C00127 HMDB03337 1.62 1.31 1.35 0.0021 0.0253 0.0244 0.3048 0.0040 0.1479 1.699281 1.050883 1.517206 1.157845 0.660732 0.490937 100 100 100 100 100 100 Amino acid Glutathione metabolism 6 535 911 215 652 103239-24-3; 1535 613.1 284 cysteine-glutathione disulfide LC/MS pos 35159 HMDB00656 0.34 1.87 1.16 < 0.001 0.0177 0.0395 0.3048 0.1335 0.3533 1.282280 3.722350 0.424587 0.227576 1.074074 0.928648 100 100 100 100 100 100 Amino acid Glutathione metabolism 4247235 13081-14-6; 821 427.1 286 S-lactoylglutathione LC/MS neg 15731 C03451 HMDB01066 9.01 0.93 1.00 < 0.001 0.0174 0.7691 0.6518 3.257548 0.361711 0.770502 0.826344 0.211200 0.211200 100 100 100 100 0 0 Amino acid Glutathione metabolism 1083 54398-03-7; 1271 378.2 296 glycylvaline LC/MS pos 18357 1.12 1.04 1.00 0.4583 0.4536 0.8823 0.6727 0.8989 0.6156 1.303928 1.160151 1.033648 0.995559 0.807191 0.806239 100 100 100 100 100 100 Peptide Dipeptide 27 248 076 994 979 1963-21-9; 1572 175.1 299 glycylproline LC/MS pos 22171 HMDB00721 1.04 1.29 0.85 0.7896 0.6025 0.1734 0.3353 0.3104 0.4539 0.878921 0.847117 1.095800 0.850831 1.425961 1.669761 100 100 100 100 100 100 Peptide Dipeptide 30 136 256 993 386 704-15-4; 1115 173.1 300 glycylisoleucine LC/MS pos 36659 0.84 1.54 0.81 0.4281 0.4395 0.3180 0.4156 0.2708 0.4224 0.873034 1.039298 1.209022 0.786328 0.755241 0.932282 50 100 100 100 100 100 Peptide Dipeptide 19461-38-2; 2080 189.1 301 glycylleucine LC/MS pos 34398 C02155 HMDB00759 1.05 1.32 0.73 0.9460 0.6554 0.2025 0.3472 0.1456 0.3665 0.997484 0.949660 1.233542 0.933157 1.341549 1.833979 100 100 100 100 100 100 Peptide Dipeptide 928 431 548 899 869-19-2; 2236 189.1 305 glycyltyrosine LC/MS pos 33958 0.79 1.69 0.74 0.4854 0.4699 0.1060 0.3048 0.3949 0.4872 0.499028 0.629482 1.230928 0.727678 1.125801 1.528535 25 100 100 100 100 100 Peptide Dipeptide 928 296 994 980 658-79-7; 1728 239.1 307 alanylalanine GC/MS 15129 C00993 HMDB03459 1.00 1.00 0.96 0.8165 0.5911 0.726770 0.726770 0.726770 0.726770 0.947432 0.984016 0 0 0 0 100 100 Peptide Dipeptide 54 603 626 992 112 1948-31-8; 1379.5 271.1 330 prolylleucine LC/MS pos 31914 0.97 1.34 0.75 0.7551 0.5872 0.0333 0.3048 0.3759 0.4872 0.875437 0.902800 1.210598 0.903271 1.166409 1.547941 100 100 100 100 100 100 Peptide Dipeptide 4 441 097 082 009 52899-07-7; 2334 229.2 339 pro-hydroxy-pro LC/MS pos 35127 HMDB06695 1.18 1.00 1.34 0.3196 0.3735 0.8162 0.6659 0.4905 0.5054 1.086688 0.922695 0.880400 0.880790 0.309943 0.231284 100 100 100 100 100 100 Peptide Dipeptide 11673055 18684-24-7; 960 229.2 345 valylglutamate LC/MS pos 32454 1.12 1.16 1.31 0.0489 0.1282 0.3679 0.4398 0.0782 0.3208 1.929576 1.730163 1.010843 0.871466 0.835106 0.635443 100 100 100 100 100 100 Peptide Dipeptide 7009623 3062-07-5; 1346 247.1 346 cysteinylglycine GC/MS 35637 C01419 HMDB00078 1.28 0.82 1.68 0.4579 0.4536 0.5592 0.5452 0.2216 0.3984 1.717401 1.344532 0.982643 1.195419 1.582813 0.940135 100 100 100 100 100 100 Peptide Dipeptide 65270 19246-18-5; 1763 257 353 cyclo(leu-pro) LC/MS pos 37104 1.00 1.00 1.52 0.1049 0.3533 0.359915 0.359915 0.359915 0.359915 0.978616 0.642013 0 0 0 0 100 100 Peptide Dipeptide 7074739 3445 211.1 354 cyclo(glu-glu) LC/MS pos 37100 1.25 1.14 1.17 0.5791 0.5112 0.5536 0.5430 0.4513 0.5054 0.980054 0.785068 0.810400 0.713839 1.063453 0.908948 50 75 75 50 100 100 Peptide Dipeptide 7408481 1595 259 360 aspartylleucine LC/MS pos 40068 1.36 1.36 0.86 0.0099 0.0654 0.5531 0.5430 0.5934 0.5403 2.729088 2.010848 0.875251 0.642985 0.721206 0.842005 100 100 75 100 100 100 Peptide Dipeptide 332962 3062-14-4; 2310 247.2 366 isoleucylglycine LC/MS pos 40008 1.31 1.46 0.91 0.0241 0.0888 0.1989 0.3472 0.3204 0.4562 2.073825 1.586319 0.746301 0.511027 0.875068 0.966616 100 100 100 100 100 100 Peptide Dipeptide 342532 868-28-0; 1732 189.2 378 leucylglycine LC/MS pos 40045 1.36 1.00 1.15 0.1280 0.2225 0.7284 0.5744 1.533772 1.130638 0.274424 0.274424 0.451070 0.392124 100 100 0 0 75 100 Peptide Dipeptide 79070 686-50-0; 1800 189.2 389 serylleucine LC/MS pos 40066 1.38 1.17 0.80 0.2289 0.3183 0.5125 0.5256 0.4538 0.5054 1.910744 1.380319 0.655167 0.559410 0.760950 0.946722 100 100 100 100 100 100 Peptide Dipeptide 6665-16-3; 2106 219.2 402 gamma-glutamylvaline LC/MS pos 32393 HMDB11172 0.65 1.62 0.63 0.0926 0.1747 0.1843 0.3468 0.0274 0.2896 0.833210 1.282198 0.953711 0.587333 0.836262 1.336708 75 100 100 75 100 100 Peptide gamma-glutamyl 2746-34-1; 2040 247.2 404 gamma-glutamylleucine LC/MS pos 18369 HMDB11171 0.78 1.16 0.72 0.1710 0.2677 0.3329 0.4215 0.1135 0.3533 1.674302 2.138379 0.645475 0.555877 0.997449 1.378334 100 100 100 100 100 100 Peptide gamma-glutamyl 151023 2566-39-4; 2744 261.2 405 gamma-glutamylisoleucine* LC/MS pos 34456 HMDB11170 0.82 1.19 0.66 0.2242 0.3183 0.0571 0.3048 0.0038 0.1479 1.306206 1.589301 0.756653 0.634322 0.879959 1.331799 100 100 100 100 100 100 Peptide gamma-glutamyl 2644 261.2 407 gamma-glutamylglycine GC/MS 33949 HMDB11667 0.51 0.91 0.87 0.1762 0.2738 0.8322 0.6666 0.7037 0.5648 1.775403 3.472058 0.440866 0.483650 0.604977 0.699005 75 100 75 50 75 75 Peptide gamma-glutamyl 165527 1948-29-4; 1934 375.2 408 gamma-glutamylmethionine LC/MS pos 37539 0.84 1.25 1.16 0.1942 0.2933 0.2877 0.3911 0.3890 0.4872 2.100752 2.487163 0.689241 0.553123 1.164837 1.000111 100 100 100 100 100 100 Peptide gamma-glutamyl 7009567 17663-87-5; 1993 279.2 409 gamma-glutamylglutamate LC/MS pos 36738 0.71 1.34 1.13 0.0147 0.0754 0.0332 0.3048 0.2431 0.3999 3.329527 4.680581 0.971172 0.724811 1.703693 1.505129 100 100 100 100 100 100 Peptide gamma-glutamyl 92865 1116-22-9; 1036 277.1 410 gamma-glutamylglutamine LC/MS pos 2730 HMDB11738 0.92 1.53 1.50 0.2556 0.3399 0.0078 0.3048 0.0010 0.1156 4.132268 4.473070 1.098718 0.717539 1.712725 1.139478 100 100 100 100 100 100 Peptide gamma-glutamyl 150914 10148-81-9; 806 276.1 412 gamma-glutamylphenylalanine LC/MS pos 33422 HMDB00594 1.01 1.25 1.06 0.9492 0.6554 0.5547 0.5430 0.5567 0.5203 1.417459 1.401384 0.498983 0.400253 0.996871 0.938162 100 100 75 75 100 100 Peptide gamma-glutamyl 111299 7432-24-8; 2846 295.1 413 gamma-glutamyltyrosine LC/MS pos 2734 1.02 1.41 1.19 0.9981 0.6657 0.2681 0.3883 0.4226 0.4979 1.888307 1.847843 0.478985 0.340120 0.892230 0.746863 100 100 100 75 100 100 Peptide gamma-glutamyl 94340 7432-23-7; 2073 311.2 449 N-acetylglucosamine GC/MS 15095 C00140 HMDB00215 0.87 0.82 0.93 0.8714 0.6432 0.6156 0.5721 0.8741 0.6117 1.322065 1.526198 0.637360 0.774659 0.610319 0.656111 75 75 50 75 75 75 Carbohydrate Aminosugars metabolism 24139 7512-17-6; 1903.3 245 453 erythronate* GC/MS 33477 HMDB00613 0.88 1.13 0.99 0.1621 0.2630 0.2771 0.3883 0.8914 0.6156 0.621209 0.708361 2.744827 2.434867 2.978786 3.023238 100 100 100 100 100 100 Carbohydrate Aminosugars metabolism 2781043 13752-84-6; 1546.9 292.1 455 N-acetylneuraminate GC/MS 1592 C00270 HMDB00230 0.88 0.81 1.31 0.3556 0.3999 0.6132 0.5721 0.3927 0.4872 1.033449 1.172951 0.582149 0.721361 1.264233 0.965873 100 100 50 75 100 75 Carbohydrate Aminosugars metabolism 131-48-6; 2074.9 245 457 Isobar: UDP-acetylglucosamine, UDPacetylgalactosamine LC/MS pos 38673 1.37 1.26 0.98 0.0015 0.0214 0.0899 0.3048 0.7933 0.5897 1.280876 0.932239 1.020805 0.811390 1.108057 1.129036 100 100 100 100 100 100 Carbohydrate Aminosugars metabolism 963 607.7 472 fructose GC/MS 31266 C00095 HMDB00660 0.82 1.06 1.31 0.4548 0.4536 0.6613 0.6028 0.3212 0.4562 1.033183 1.255754 0.921703 0.867236 0.206569 0.157170 100 100 100 100 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 5984 57-48-7; 1762.7 204 473 galactitol (dulcitol) GC/MS 1117 C01697 HMDB00107 1.00 0.98 0.66 0.7738 0.6518 0.1510 0.3675 0.528106 0.528106 0.971202 0.995177 0.887196 1.342824 0 0 100 100 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 11850 608-66-2; 1849.2 319.1 474 galactose GC/MS 12055 C01582 HMDB00143 1.00 0.94 0.98 0.8894 0.6440 0.7883 0.6554 0.6644 0.5554 1.890737 1.883678 0.438061 0.466281 0.959648 0.983953 100 100 75 100 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 3037556 59-23-4; 1793.8 203.9 480 6'-sialyllactose GC/MS 39795 G00265 HMDB06569 2.12 1.90 0.80 0.0535 0.1343 0.2202 0.3613 0.8560 0.6058 1.590351 0.751930 2.218155 1.168507 1.224352 1.538291 100 75 100 100 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 35890-39-2; 2071.5 285.1 483 mannitol GC/MS 15335 C00392 HMDB00765 0.72 1.01 0.82 0.1898 0.2930 0.8206 0.6659 0.2219 0.3984 0.966753 1.345323 1.047343 1.040583 0.629613 0.771903 100 100 100 100 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 6251 69-65-8; 1839 319.1 487 mannose GC/MS 584 C00159 HMDB00169 0.82 1.24 1.38 0.2815 0.3613 0.0486 0.3048 0.0431 0.2896 1.431811 1.756323 1.009769 0.817125 0.298694 0.216400 100 100 100 100 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 161658 3458-28-4; 1753.5 203.9 489 mannose-6-phosphate GC/MS 1470 C00275 HMDB01078 1.03 1.25 1.15 0.9683 0.6582 0.3098 0.4094 0.1387 0.3573 3.648592 3.557151 2.128050 1.704312 0.106095 0.092368 100 100 100 100 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 70442-25-0;104872-94-8; 2035.9 387.2 494 stachyose LC/MS neg 15960 C01613 HMDB03553 1.00 1.00 1.41 0.0617 0.2896 0.593320 0.593320 0.593320 0.593320 1.049410 0.745369 0 0 0 0 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 10094-58-3; 932 665.2 495 sorbitol GC/MS 15053 C00794 HMDB00247 0.70 1.33 1.05 0.2015 0.2965 0.0572 0.3048 0.7022 0.5648 3.180332 4.525931 1.438845 1.085023 0.535513 0.510241 100 100 100 100 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 107428 6706-59-8; 1843 319.1 499 sucrose LC/MS neg 1519 C00089 HMDB00258 1.00 1.00 1.39 0.0632 0.2896 0.553182 0.553182 0.553182 0.553182 1.006817 0.726851 0 0 0 0 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 5988 57-50-1; 875 341.2 506 raffinose LC/MS neg 586 C00492 HMDB03213 1.00 1.00 1.39 0.0355 0.2896 0.553968 0.553968 0.553968 0.553968 1.027454 0.740960 0 0 0 0 100 100 Carbohydrate Fructose, mannose, galactose, starch, and sucrose metabolism 439242 17629-30-0; 997 503.2 517 glycerate GC/MS 1572 C00258 HMDB00139 1.00 1.13 1.58 0.9240 0.6524 0.4779 0.4987 0.0024 0.1339 1.725005 1.721453 0.641160 0.566918 0.494863 0.313270 100 100 100 100 100 100 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 752 600-19-1; 1360.7 189 519 glucose-6-phosphate (G6P) GC/MS 31260 C00668 HMDB01401 1.01 1.37 1.01 0.9529 0.6554 0.1185 0.3048 0.8922 0.6156 6.295670 6.216681 4.040949 2.954796 0.016500 0.016394 100 100 100 100 100 100 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 103192-55-8; 2042.7 387.2 520 glucose 1-phosphate GC/MS 33755 C00103 HMDB01586 1.06 1.36 1.03 0.7099 0.5760 0.0350 0.3048 0.7573 0.5805 4.257010 4.033722 1.325115 0.975774 0.546891 0.533055 100 100 100 100 100 100 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 65533 56401-20-8; 1853 217.1 521 glucose GC/MS 20488 C00293 HMDB00122 0.84 0.89 1.90 0.4204 0.4356 0.7754 0.6518 0.0146 0.2896 0.700004 0.828772 0.746642 0.837354 0.117640 0.061792 100 100 100 100 100 100 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 79025 50-99-7; 1866.8 217.1 524 fructose-6-phosphate GC/MS 12021 C05345 HMDB00124 0.78 1.51 1.11 0.4699 0.4594 0.3420 0.4238 0.6622 0.5554 3.921782 5.008276 3.263801 2.165308 0.033518 0.030237 100 100 100 100 75 100 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 103213-47-4; 1994.9 315.1 527 Isobar: fructose 1,6-diphosphate, glucose 1,6- diphosphate, myo-inositol 1,4 or 1,3-diphosphate LC/MS neg 36984 1.61 1.25 1.56 0.0398 0.1170 0.2799 0.3883 0.0647 0.2896 25.004920 15.575880 0.613371 0.490887 0.036806 0.023520 100 100 100 100 100 50 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 572 339 529 3-phosphoglycerate GC/MS 40264 C00597 HMDB00807 1.76 1.40 1.59 0.0824 0.1633 0.1899 0.3472 0.0707 0.3011 0.496099 0.282137 1.357233 0.970463 0.934291 0.588475 100 100 100 100 100 100 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 80731-10-8; 1756 357.1 531 dihydroxyacetone phosphate (DHAP) GC/MS 15522 C00111 HMDB01473 1.25 0.99 1.00 0.5323 0.4874 0.9768 0.6978 2.071167 1.656921 0.434371 0.438162 0.331005 0.331005 100 100 50 75 0 0 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 4643300 102783-56-2; 1737 315.1 532 1,3-dihydroxyacetone GC/MS 35963 C00184 HMDB01882 1.13 1.00 1.00 0.7615 0.5897 1.092791 0.967218 0.597206 0.597206 0.597206 0.597206 100 100 0 0 0 0 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 670 62147-49-3; 1263 103 534 phosphoenolpyruvate (PEP) GC/MS 597 C00074 HMDB00263 1.00 1.00 1.00 0.660569 0.660569 0.660569 0.660569 0.660569 0.660569 0 0 0 0 0 0 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 1005 10526-80-4; 1595.4 369 536 lactate GC/MS 527 C00186 HMDB00190 0.93 1.17 1.01 0.3199 0.3735 0.2748 0.3883 0.7461 0.5752 0.993239 1.066442 1.623043 1.384805 1.842177 1.816482 100 100 100 100 100 100 Carbohydrate Glycolysis, gluconeogenesis, pyruvate metabolism 612 79-33-4; 1102.8 116.9 546 arabitol GC/MS 38075 C00474 HMDB01851 0.79 1.25 0.93 0.1960 0.2933 0.0800 0.3048 0.6208 0.5476 0.684578 0.861840 1.412379 1.132836 1.452401 1.564196 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 94154 488-82-4; 1687.5 307.1 548 ribitol GC/MS 15772 C00474 HMDB00508 0.88 1.19 1.08 0.5258 0.4855 0.3395 0.4229 0.5841 0.5369 0.785967 0.894635 1.653469 1.389979 1.508502 1.392481 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 488-81-3; 1692.4 217 549 threitol GC/MS 35854 C16884 HMDB04136 0.81 1.24 1.18 0.2004 0.2965 0.2029 0.3472 0.0551 0.2896 0.970388 1.198811 1.438181 1.162318 0.996745 0.841204 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 169019 2418-52-2; 1513 217.1 551 sedoheptulose-7-phosphate GC/MS 35649 C05382 HMDB01068 0.83 1.45 1.53 0.4017 0.4236 0.0933 0.3048 0.0526 0.2896 1.018539 1.225809 2.245590 1.550703 0.564271 0.369676 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 616 2646-35-7; 2070 691.35 554 ribose GC/MS 12080 C00121 HMDB00283 0.96 1.18 0.98 0.7321 0.5812 0.1708 0.3353 0.8754 0.6117 2.216973 2.314451 1.126051 0.956348 0.452296 0.459362 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 5311110 50-69-1; 1639.2 204 557 ribose 5-phosphate GC/MS 561 C00117 HMDB00618 0.90 1.41 1.62 0.5448 0.4948 0.4130 0.4746 0.0912 0.3258 1.202360 1.340732 1.201419 0.849570 0.183607 0.113382 100 100 100 100 100 75 Carbohydrate Nucleotide sugars, pentose metabolism 447634 18265-46-8;108321-05-7; 1928.4 315.1 559 ribulose GC/MS 35855 C00309 HMDB00621,HM DB03371 0.64 1.15 0.93 0.0793 0.1621 0.5655 0.5468 0.9332 0.6255 2.062026 3.223146 0.785684 0.681195 1.042619 1.115630 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 79021 488-84-6; 1662 306.1 561 Isobar: ribulose 5-phosphate, xylulose 5-phosphate GC/MS 37288 0.95 1.17 1.16 0.6572 0.5453 0.3036 0.4043 0.3405 0.4653 1.634048 1.721292 1.001907 0.859162 0.093934 0.081022 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 1935 357.2 562 UDP-glucose GC/MS 32344 C00029 HMDB00286 1.03 1.15 1.06 0.6997 0.5719 0.7733 0.6518 0.4997 0.5054 1.077929 1.042431 0.660038 0.572956 1.354972 1.283323 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 8629 117756-22-6; 1986 243.1 563 UDP-glucuronate GC/MS 34377 C00167 HMDB00935 0.84 1.05 1.17 0.3569 0.3999 0.6851 0.6127 0.1473 0.3665 1.073699 1.282656 1.189633 1.131029 0.908326 0.774416 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 17473 28053-08-9;63700-19-6; 1957 315.2 565 xylitol GC/MS 4966 C00379 HMDB00568 0.62 0.96 0.72 0.0121 0.0704 0.7294 0.6327 0.0495 0.2896 1.077380 1.737788 0.556719 0.581260 0.945914 1.320577 100 100 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 6912 87-99-0; 1677.6 307.2 566 arabinose GC/MS 575 C00181 HMDB00646 1.00 1.14 0.68 0.9971 0.6657 0.5502 0.5430 0.0618 0.2896 0.948437 0.946852 0.970891 0.853379 0.744819 1.098954 75 75 75 50 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 66308 28697-53-2; 1631.6 217 570 xylonate GC/MS 35638 C00502,C05 411 1.00 1.30 0.97 0.1220 0.3048 0.8889 0.6156 0.673016 0.673016 1.254603 0.963323 0.899027 0.922239 0 0 100 100 100 100 Carbohydrate Nucleotide sugars, pentose metabolism 6602431 73686-31-7; 1722 292 571 xylulose GC/MS 18344 C00310 HMDB00654 0.62 1.00 1.00 0.1029 0.1876 0.697149 1.118323 0.330288 0.330288 0.330288 0.330288 100 100 0 0 0 0 Carbohydrate Nucleotide sugars, pentose metabolism 5289590 551-84-8; 1668 306.1 576 Nucleotide sugars UDP-galactose GC/MS 15860 C00052 HMDB000302 0.92 1.19 1.04 0.7432 0.5816 0.4366 0.4900 0.6675 0.5559 0.783025 0.848230 1.124911 0.948700 1.891893 1.810731 100 100 100 100 100 100 Carbohydrate Nucleotide sugars 18068 2956-16-3;91183-98-1; 1973 243.1 579 citrate GC/MS 1564 C00158 HMDB00094 0.79 0.98 1.32 0.0455 0.1257 0.8789 0.6727 0.1590 0.3681 1.059870 1.343827 1.125088 1.146681 0.691614 0.524978 100 100 100 100 100 100 Energy Krebs cycle 311 77-92-9; 1763.4 273.1 590 succinate GC/MS 1437 C00042 HMDB00254 1.53 1.48 1.13 0.1473 0.2428 0.0242 0.3048 0.6777 0.5614 0.630332 0.412688 0.292774 0.197482 11.570440 10.200260 100 100 100 100 100 100 Energy Krebs cycle 1110 110-15-6; 1348 247 594 fumarate GC/MS 1643 C00122 HMDB00134 0.77 1.15 1.12 0.0781 0.1621 0.6610 0.6028 0.6166 0.5476 0.896630 1.168011 1.493859 1.298764 2.619577 2.338317 100 100 100 100 100 100 Energy Krebs cycle 100-17-8; 1382.1 245 598 malate GC/MS 1303 C00149 HMDB00156 0.94 1.24 1.09 0.6189 0.5215 0.1313 0.3048 0.0549 0.2896 1.120411 1.191699 1.083672 0.875328 1.670064 1.538071 100 100 100 100 100 100 Energy Krebs cycle 525 6915-15-7; 1502 233 601 acetylphosphate GC/MS 15488 C00227 HMDB01494 1.58 1.63 1.11 0.0197 0.0819 0.0679 0.3048 0.4890 0.5054 1.000088 0.632120 1.582798 0.970047 0.631816 0.567069 100 100 100 100 100 100 Energy Oxidative phosphorylation 186 94249-01-1; 1263 211 602 phosphate GC/MS 11438 C00009 HMDB01429 1.26 1.23 1.17 0.0093 0.0654 0.1596 0.3274 0.0293 0.2896 0.872365 0.694668 1.156307 0.940602 0.867987 0.742763 100 100 100 100 100 100 Energy Oxidative phosphorylation 1061 7664-38-2 ; 1307.7 298.9 603 pyrophosphate (PPi) GC/MS 2078 C00013 HMDB00250 1.16 2.32 1.16 0.8763 0.6440 0.0471 0.3048 0.5176 0.5074 1.259026 1.087276 2.036613 0.879187 0.695658 0.599078 100 100 100 100 100 100 Energy Oxidative phosphorylation 644102 1466-09-3; 1642.3 451 604 linoleate (18:2n6) LC/MS neg 1105 C01595 HMDB00673 1.21 1.21 1.20 0.0787 0.1621 0.0588 0.3048 0.0998 0.3508 1.358680 1.123602 0.973607 0.801889 0.824386 0.685709 100 100 100 100 100 100 Lipid Essential fatty acid 5280450 60-33-3; 5533 279.3 608 linolenate [alpha or gamma; (18:3n3 or 6)] LC/MS neg 34035 C06427 HMDB01388 1.27 1.42 1.18 0.1648 0.2636 0.0112 0.3048 0.1312 0.3533 1.600506 1.257886 1.347180 0.951987 0.768562 0.652776 100 100 100 100 100 100 Lipid Essential fatty acid 5450 277.3 609 dihomo-linolenate (20:3n3 or n6) LC/MS neg 35718 C03242 HMDB02925 1.68 1.24 1.36 0.0070 0.0560 0.0372 0.3048 0.0293 0.2896 1.028317 0.611047 1.632507 1.314719 0.529269 0.388671 100 100 100 100 100 100 Lipid Essential fatty acid 5312529 5600 305.4 610 eicosapentaenoate (EPA; 20:5n3) LC/MS neg 18467 C06428 HMDB01999 1.34 1.43 1.11 0.1640 0.2636 0.0283 0.3048 0.2341 0.3990 2.993011 2.232129 0.955418 0.666491 0.457535 0.413638 100 100 100 100 100 100 Lipid Essential fatty acid 446284 10-2005-9;10417-94-4; 5442 301.3 611 docosapentaenoate (n3 DPA; 22:5n3) LC/MS neg 32504 C16513 HMDB01976 1.49 1.26 1.21 0.0263 0.0937 0.0324 0.3048 0.1123 0.3533 3.095177 2.083391 1.058121 0.838536 0.433281 0.356939 100 100 100 100 100 100 Lipid Essential fatty acid 2234-74-4 ; 5574 329.4 612 docosapentaenoate (n6 DPA; 22:5n6) LC/MS neg 37478 C06429 HMDB13123 1.68 1.33 1.22 0.0043 0.0418 0.0929 0.3048 0.2990 0.4459 1.875670 1.116000 1.166829 0.874240 0.354899 0.291003 100 100 100 100 100 100 Lipid Essential fatty acid 6441454 25182-74-5; 5625 329.4 613 docosahexaenoate (DHA; 22:6n3) LC/MS neg 19323 C06429 HMDB02183 1.09 1.33 1.09 0.4988 0.4728 0.0147 0.3048 0.3940 0.4872 2.622188 2.416629 1.083500 0.814852 0.417781 0.383123 100 100 100 100 100 100 Lipid Essential fatty acid 445580 6217-54-5; 5518 327.3 620 caprylate (8:0) LC/MS neg 32492 C06423 HMDB00482 1.22 1.35 1.49 0.4267 0.4395 0.2108 0.3508 0.1234 0.3533 0.956283 0.782361 0.905127 0.669698 1.123158 0.753992 100 100 100 100 100 100 Lipid Medium chain fatty acid 379 124-07-2; 4367 143.2 621 pelargonate (9:0) LC/MS neg 12035 C01601 HMDB00847 1.38 1.20 1.21 0.0028 0.0313 0.3257 0.4211 0.1351 0.3533 1.035260 0.749882 0.968227 0.803915 0.604232 0.500835 100 100 100 100 100 100 Lipid Medium chain fatty acid 5461016 112-05-0; 4847 157.2 622 caprate (10:0) LC/MS neg 1642 C01571 HMDB00511 1.31 1.18 1.20 0.0101 0.0654 0.2652 0.3883 0.1279 0.3533 1.009006 0.770616 0.886396 0.748761 0.581897 0.485023 100 100 100 100 100 100 Lipid Medium chain fatty acid 2969 112-37-8; 5092 171.2 625 laurate (12:0) LC/MS neg 1645 C02679 HMDB00638 1.29 1.21 1.12 0.0830 0.1633 0.2488 0.3844 0.3058 0.4516 0.984387 0.761229 0.929418 0.770225 0.563251 0.502712 100 100 100 100 100 100 Lipid Medium chain fatty acid 3893 143-07-7; 5288 199.3 629 myristate (14:0) LC/MS neg 1365 C06424 HMDB00806 1.20 1.19 1.09 0.0170 0.0798 0.1995 0.3472 0.2296 0.3984 1.027143 0.856031 0.978460 0.821194 0.688916 0.630695 100 100 100 100 100 100 Lipid Long chain fatty acid 11005 544-63-8; 5439 227.3 630 myristoleate (14:1n5) LC/MS neg 32418 C08322 HMDB02000 1.29 1.42 1.00 0.2583 0.3414 0.0320 0.3048 0.9104 0.6156 0.994122 0.771506 1.136240 0.802051 0.526568 0.524454 100 100 100 100 100 100 Lipid Long chain fatty acid 5281119 544-64-9 ; 5338 225.3 631 pentadecanoate (15:0) GC/MS 1361 C16537 HMDB00826 1.24 1.20 0.99 0.3228 0.3750 0.1969 0.3472 0.9965 0.6399 1.270112 1.023067 0.933029 0.780574 0.582156 0.589856 100 100 100 100 100 100 Lipid Long chain fatty acid 13849 1002-84-2; 1853.5 299.2 632 palmitate (16:0) LC/MS neg 1336 C00249 HMDB00220 1.25 1.17 1.07 0.0450 0.1257 0.1508 0.3203 0.3992 0.4872 1.207762 0.968563 0.795248 0.681133 0.570380 0.531471 100 100 100 100 100 100 Lipid Long chain fatty acid 985 57-10-3; 5619 255.3 633 palmitoleate (16:1n7) LC/MS neg 33447 C08362 HMDB03229 1.10 1.21 1.10 0.4030 0.4236 0.0459 0.3048 0.2387 0.3999 1.178972 1.074909 1.052187 0.866002 0.469688 0.425952 100 100 100 100 100 100 Lipid Long chain fatty acid 445638 373-49-9; 5477 253.3 635 margarate (17:0) LC/MS neg 1121 HMDB02259 1.51 1.24 1.10 0.0410 0.1191 0.1389 0.3085 0.3912 0.4872 1.474822 0.975225 0.903355 0.727916 0.446201 0.406368 100 100 100 100 100 100 Lipid Long chain fatty acid 10465 506-12-7; 5733 269.3 636 10-heptadecenoate (17:1n7) LC/MS neg 33971 1.16 1.21 1.22 0.3031 0.3679 0.1120 0.3048 0.0581 0.2896 1.614897 1.390089 1.131086 0.932439 0.623024 0.509790 100 100 100 100 100 100 Lipid Long chain fatty acid 5312435 29743-97-3; 5558 267.3 637 stearate (18:0) LC/MS neg 1358 C01530 HMDB00827 1.43 1.17 1.10 0.0645 0.1529 0.1245 0.3048 0.2138 0.3984 1.252209 0.877905 0.959595 0.816805 0.549077 0.497659 100 100 100 100 100 100 Lipid Long chain fatty acid 5281 57-11-4; 5886 283.4 Mean Values % Filled Values THP mir Contr Mec1 mir-125b Mec1 mir Contr Mec2 mir-125b Mec2 mir Contr Mec2 mir Contr Table S5: Heat map of statistically significant biochemicals profiled in this study. For paired comparisons, shaded cells indicate p 0.05 (red indicates that the mean values are significantly higher for that comparison; green values significantly lower). Blue-bolded text indicates 0.05< p< 0.10. All data normalized using Bradford protein concentration. Fold of Change Statistical Value Welch's Two-Sample t-test Welch's Two-Sample t-test HMDB THP mir-125b THP mir Contr Mec1 mir-125b Mec1 mir Contr Mec2 mir-125b Mec2 mir Contr PATHWAY SORT SUPER PATHWAY SUB PATHWAY BIOCHEMICAL NAME PLATFORM COMP ID KEGG THP mir-125b THP mir-125b / THP mir Contr Mec1 mir-125b / Mec1 mir Contr Mec2 mir-125b / Mec2 mir Contr CAS RI MASS Glycine, serine and threonine metabolism Super Pathway Sub Pathway PUBCHEM Mec1 mir-125b Mec1 mir Contr Mec2 mir-125b THP mir-125b THP mir Contr Guanidino and acetamido metabolism Glutathione metabolism Peptide Dipeptide gamma-glutamyl Carbohydrate Aminosugars metabolism Fructose, mannose, galactose, starch, and sucrose metabolism Glycolysis, gluconeogenesis, pyruvate metabolism Nucleotide sugars, pentose metabolism Amino acid Cysteine, methionine, SAM, taurine metabolism Urea cycle; arginine-, proline-, metabolism Creatine metabolism Polyamine metabolism Tryptophan metabolism Valine, leucine and isoleucine metabolism Alanine and aspartate metabolism Glutamate metabolism Histidine metabolism Lysine metabolism Phenylalanine & tyrosine metabolism Energy Krebs cycle Oxidative phosphorylation Essential fatty acid Medium chain fatty acid Long chain fatty acid

639 oleate (18:1n9) GC/MS 1359 C00712 HMDB00207 1.14 1.18 1.05 0.1710 0.2677 0.0952 0.3048 0.5102 0.5054 1.113520 0.979590 1.034050 0.874486 0.842447 0.804602 100 100 100 100 100 100 Lipid Long chain fatty acid 445639 112-80-1; 1984.4 339.2 641 cis-vaccenate (18:1n7) GC/MS 33970 C08367 1.12 1.20 1.15 0.2212 0.3170 0.0761 0.3048 0.0397 0.2896 1.052082 0.941891 0.971098 0.808195 0.814800 0.709220 100 100 100 100 100 100 Lipid Long chain fatty acid 5282761 693-72-1; 1987 339.3 643 13-octadecenoate (18:1n5) GC/MS 17804 0.98 1.08 1.05 0.8867 0.6440 0.4416 0.4909 0.6581 0.5547 0.810603 0.826693 1.015598 0.942374 0.949170 0.907694 100 75 100 100 100 100 Lipid Long chain fatty acid 5312441 13126-39-1; 1993.4 339.3 648 10-nonadecenoate (19:1n9) LC/MS neg 33972 1.32 1.29 1.09 0.0580 0.1422 0.1277 0.3048 0.4967 0.5054 1.163906 0.882886 1.320705 1.026087 0.966592 0.890218 100 100 100 100 100 100 Lipid Long chain fatty acid 5312513 73033-09-7; 5775 295.4 653 eicosenoate (20:1n9 or 11) LC/MS neg 33587 HMDB02231 1.24 1.20 1.15 0.1393 0.2345 0.0832 0.3048 0.2303 0.3984 0.869281 0.701413 1.297313 1.081130 1.262125 1.095200 100 100 100 100 100 100 Lipid Long chain fatty acid 5955 309.4 655 dihomo-linoleate (20:2n6) LC/MS neg 17805 C16525 1.22 1.18 1.13 0.1915 0.2933 0.1516 0.3203 0.3544 0.4743 0.822339 0.675211 2.316750 1.963487 1.487656 1.311998 100 100 100 100 100 100 Lipid Long chain fatty acid 6439848 2091-39-6; 5722 307.3 659 arachidonate (20:4n6) LC/MS neg 1110 C00219 HMDB01043 1.49 1.31 1.26 0.0209 0.0841 0.0127 0.3048 0.0240 0.2896 1.374857 0.924043 1.110953 0.848864 0.341360 0.270820 100 100 100 100 100 100 Lipid Long chain fatty acid 444899 506-32-1; 5525 303.4 663 docosadienoate (22:2n6) LC/MS neg 32415 C16533 1.14 1.16 1.09 0.5911 0.5157 0.4742 0.4987 0.6137 0.5476 0.808852 0.712121 1.782866 1.543290 1.636383 1.502612 100 100 100 100 100 100 Lipid Long chain fatty acid 5282807 7370-49-2 ; 6017 335.4 664 docosatrienoate (22:3n3) LC/MS neg 32417 C16534 HMDB02823 1.38 1.01 1.14 0.1133 0.2017 0.8689 0.6727 0.1828 0.3681 0.806554 0.583815 1.795739 1.784806 1.792102 1.569099 100 100 100 100 100 100 Lipid Long chain fatty acid 5312556 59708-86-0 ; 5825 333.4 665 adrenate (22:4n6) LC/MS neg 32980 C16527 HMDB02226 1.98 1.24 1.30 0.0152 0.0754 0.1400 0.3085 0.0494 0.2896 1.306173 0.661328 1.075463 0.866661 0.376873 0.289920 100 100 100 100 100 100 Lipid Long chain fatty acid 5282844 2091-25-0; 5684 331.3 679 Fatty acid, methyl ester methyl stearate GC/MS 6097 1.17 1.32 1.37 0.7667 0.5917 0.5452 0.5430 0.1812 0.3681 0.885240 0.759321 1.477220 1.117073 0.921393 0.672189 75 75 100 100 100 100 Lipid Fatty acid, methyl ester 8201 112-61-8; 1946.4 73.9 692 4-hydroxybutyrate (GHB) GC/MS 34585 C00989 HMDB00710 0.86 1.25 1.23 0.3441 0.3894 0.2382 0.3704 0.0593 0.2896 0.987242 1.152585 0.842437 0.671679 1.312420 1.068593 100 100 100 100 100 100 Lipid Fatty acid, monohydroxy 10413 502-85-2; 1277 233.1 706 2-hydroxypalmitate LC/MS neg 35675 1.23 1.01 1.35 0.7028 0.5723 0.9106 0.6829 0.0760 0.3177 0.709139 0.576458 0.766133 0.762296 1.416533 1.047394 100 100 100 100 100 100 Lipid Fatty acid, monohydroxy 92836 764-67-0; 5508 271.3 713 adipate GC/MS 21134 C06104 HMDB00448 0.56 0.97 1.19 0.0018 0.0234 0.8929 0.6743 0.1154 0.3533 0.839944 1.512609 0.937784 0.967229 1.114447 0.938382 100 100 100 100 100 100 Lipid Fatty acid, dicarboxylate 196 124-04-9; 1522.2 110.9 714 2-hydroxyglutarate GC/MS 37253 C02630 HMDB00606 0.97 1.21 1.13 0.7929 0.6025 0.1917 0.3472 0.1637 0.3681 2.860829 2.950557 0.976378 0.809723 2.396589 2.119816 100 100 100 100 100 100 Lipid Fatty acid, dicarboxylate 43 40951-21-1; 1576 247 721 azelate (nonanedioate) LC/MS neg 18362 C08261 HMDB00784 1.22 0.88 0.79 0.9972 0.6657 0.6403 0.5904 0.3115 0.4539 1.266216 1.036471 0.666907 0.758380 0.380362 0.481378 75 100 75 100 50 100 Lipid Fatty acid, dicarboxylate 2266 123-99-9; 1322 187.2 731 oleamide GC/MS 27409 HMDB02117 1.07 0.90 1.42 0.8027 0.6025 0.6792 0.6099 0.1727 0.3681 0.957404 0.891509 0.759053 0.841853 0.770076 0.540817 100 100 50 75 100 75 Lipid Fatty acid, amide 5283387 301-02-0; 2062.5 338.3 733 stearamide GC/MS 37487 C13846 1.00 0.77 0.75 0.4640 0.4987 0.4781 0.5054 0.383664 0.383664 0.498591 0.644113 0.591494 0.793487 0 0 50 75 100 75 Lipid Fatty acid, amide 31292 124-26-5; 2071 131 744 Fatty acid, branched methyl palmitate (15 or 2) LC/MS neg 38768 1.18 1.11 1.00 0.3968 0.4236 0.2809 0.3883 0.9776 0.6353 1.170589 0.994641 0.728880 0.657271 0.583346 0.581043 100 100 100 100 100 100 Lipid Fatty acid, branched 5698 269.4 802 oleic ethanolamide LC/MS neg 38102 HMBD02088 1.00 1.00 1.11 0.3776 0.4872 0.848897 0.848897 0.848897 0.848897 1.064701 0.956361 0 0 0 0 100 100 Lipid Endocannabinoid 5283454 11-58-0;111-58-0; 6553 324.5 803 palmitoyl ethanolamide LC/MS neg 38165 1.37 1.27 1.27 0.0888 0.1689 0.1039 0.3048 0.2306 0.3984 0.597736 0.436350 1.769366 1.390913 0.842982 0.661789 100 100 100 100 100 100 Lipid Endocannabinoid 4671 6416 298.4 804 stearoyl ethanolamide LC/MS pos 38625 1.00 0.72 0.90 0.6062 0.5700 0.5911 0.5403 0.228161 0.228161 0.929345 1.296640 0.911026 1.013198 0 0 75 100 75 100 Lipid Endocannabinoid 27902 111-57-9; 5968.9 328.3 809 propionylcarnitine LC/MS pos 32452 C03017 HMDB00824 1.44 1.36 1.25 0.0092 0.0654 0.1254 0.3048 0.1192 0.3533 1.257724 0.871643 0.590578 0.435032 0.397286 0.318970 100 100 100 100 100 100 Lipid Fatty acid metabolism (also BCAA metabolism) 107738 17298-37-2 ; 1589 218.2 811 butyrylcarnitine LC/MS pos 32412 2.01 1.07 1.75 < 0.001 0.0177 0.7632 0.6508 0.0272 0.2896 2.148102 1.067586 1.229464 1.143816 0.321864 0.184417 100 100 100 100 100 100 Lipid Fatty acid metabolism (also BCAA metabolism) 213144 25576-40-3; 2007 232.2 819 deoxycarnitine LC/MS pos 36747 C01181 HMDB01161 1.34 1.21 0.94 0.0153 0.0754 0.0826 0.3048 0.6329 0.5476 1.626518 1.212619 1.282035 1.056071 0.767193 0.820475 100 100 100 100 100 100 Lipid Carnitine metabolism 725 6249-56-5; 759 146.1 820 carnitine LC/MS pos 15500 1.16 1.20 0.89 0.0378 0.1144 0.0985 0.3048 0.2030 0.3876 6.075236 5.237598 1.390596 1.160655 0.875469 0.986600 100 100 100 100 100 100 Lipid Carnitine metabolism 10917 461-05-2; 702 162.2 821 3-dehydrocarnitine* LC/MS pos 32654 C02636 HMDB12154 1.10 1.32 0.93 0.2676 0.3495 0.1521 0.3203 0.7478 0.5752 7.163294 6.486171 1.130048 0.858899 0.579268 0.619864 100 100 100 100 100 100 Lipid Carnitine metabolism 6991982 10457-99-5; 1020 160.2 822 acetylcarnitine LC/MS pos 32198 C02571 HMDB00201 1.56 1.14 1.69 < 0.001 0.0036 0.3851 0.4533 < 0.001 0.1074 2.937081 1.887309 0.999991 0.880478 0.144076 0.085318 100 100 100 100 100 100 Lipid Carnitine metabolism 7045767 5080-50-2; 1203 204.2 833 palmitoylcarnitine LC/MS pos 22189 1.38 1.27 1.29 0.6046 0.5215 0.4315 0.4867 0.4849 0.5054 3.835929 2.783688 1.276825 1.007871 0.282314 0.219591 100 100 100 100 100 100 Lipid Carnitine metabolism 461 6865-14-1; 5179 400.4 834 stearoylcarnitine LC/MS pos 34409 HMDB00848 1.81 1.41 1.11 0.3138 0.3735 0.3635 0.4382 0.8321 0.5933 3.795447 2.092499 0.925854 0.655876 0.223281 0.201418 100 100 100 100 50 100 Lipid Carnitine metabolism 18822-91-8; 5300 428.4 835 oleoylcarnitine LC/MS pos 35160 HMDB05065 1.22 1.12 1.00 0.7295 0.5812 0.9522 0.6906 1.351362 1.104111 0.535345 0.478734 0.237040 0.237040 100 100 75 100 0 0 Lipid Carnitine metabolism 5202 426.4 840 glycocholate LC/MS neg 18476 C01921 HMDB00138 0.95 1.24 1.36 0.7723 0.5939 0.1573 0.3254 0.3213 0.4562 0.485442 0.509014 1.145009 0.922071 0.313320 0.230417 50 75 100 100 75 50 Lipid Bile acid metabolism 10140 475-31-0;863-57-0; 5104 464.4 841 taurocholate LC/MS neg 18497 C05122 HMDB00036 0.72 1.12 1.19 0.2430 0.3311 0.3925 0.4533 0.1936 0.3828 0.393753 0.549982 1.115489 0.995009 0.243213 0.204995 50 100 100 100 75 75 Lipid Bile acid metabolism 145-42-6; 5122 514.3 843 taurochenodeoxycholate LC/MS neg 18494 C05465 HMDB00951 0.63 1.27 1.33 0.0605 0.1468 0.1236 0.3048 0.2284 0.3984 0.218031 0.346123 1.171297 0.922866 0.218191 0.163676 100 100 100 100 100 100 Lipid Bile acid metabolism 387316 6009-98-9; 5218 498.3 847 deoxycholate LC/MS neg 1114 C04483 HMDB00626 0.55 1.58 1.03 < 0.001 0.0036 0.0386 0.3048 0.8330 0.5933 3.888835 7.106324 1.173498 0.742084 0.112690 0.109634 100 100 100 100 100 100 Lipid Bile acid metabolism 440355 83-44-3; 5268 391.4 848 taurodeoxycholate LC/MS neg 12261 C05463 HMDB00896 0.89 1.30 1.29 0.6131 0.5215 0.2369 0.3704 0.3267 0.4590 0.150269 0.169094 1.367619 1.048576 0.174052 0.134979 75 100 100 100 100 100 Lipid Bile acid metabolism 2733768 207737-97-1; 5243 498.3 851 glycochenodeoxycholate LC/MS neg 32346 C05466 HMDB00637 0.86 1.34 1.22 0.2081 0.3042 0.0789 0.3048 0.1753 0.3681 0.312693 0.363708 1.226584 0.915570 0.194577 0.158855 100 100 100 100 100 100 Lipid Bile acid metabolism 16564-43-5; 5245 448.4 874 Fatty alcohol, long chain 1-octadecanol GC/MS 21128 D01924 HMDB02350 1.33 1.25 1.17 0.0378 0.1144 0.1807 0.3439 0.0442 0.2896 1.102592 0.829660 0.869789 0.696930 0.523402 0.445817 100 100 100 100 100 100 Lipid Fatty alcohol, long chain 8221 112-92-5; 1957.7 327.3 875 choline phosphate LC/MS pos 34396 2.41 1.19 1.16 < 0.001 0.0036 0.2359 0.3704 0.0239 0.2896 1.678730 0.695305 1.718706 1.438391 0.913883 0.785955 100 100 100 100 100 100 Lipid Glycerolipid metabolism 135437 72556-74-2; 695 184.1 876 ethanolamine GC/MS 1497 C00189 HMDB00149 0.77 1.20 0.75 0.2517 0.3387 0.3289 0.4215 0.3990 0.4872 1.288272 1.681879 0.999528 0.833221 1.633126 2.164424 100 100 100 100 100 100 Lipid Glycerolipid metabolism 141-43-5; 1304 174.1 877 phosphoethanolamine GC/MS 12102 C00346 HMDB00224 1.31 1.20 1.24 0.0133 0.0751 0.4183 0.4784 0.1609 0.3681 1.579144 1.201763 1.462039 1.221313 1.148867 0.929485 100 100 100 100 100 100 Lipid Glycerolipid metabolism 52 323 241 015 1071-23-4; 1577.3 299.1 878 glycerophosphoethanolamine GC/MS 37455 C01233 HMDB00114 0.38 2.14 0.73 0.2159 0.3114 0.5187 0.5274 0.6962 0.5648 0.740502 1.949211 0.115006 0.053675 1.067317 1.468927 75 100 50 50 100 75 Lipid Glycerolipid metabolism 123874 33049-08-0; 1906 357.1 882 glycerol 3-phosphate (G3P) GC/MS 15365 C00093 HMDB00126 1.36 1.22 1.14 0.0174 0.0798 0.2143 0.3540 0.5347 0.5127 1.794343 1.323181 0.541002 0.442791 0.856380 0.750455 100 100 100 100 100 100 Lipid Glycerolipid metabolism 754 29849-82-9; 1719.7 357.1 883 glycerophosphorylcholine (GPC) LC/MS pos 15990 C00670 HMDB00086 2.26 1.18 1.12 < 0.001 0.0177 0.3347 0.4215 0.6320 0.5476 2.978882 1.315798 0.201281 0.171189 0.698955 0.624604 100 100 100 100 100 100 Lipid Glycerolipid metabolism 657272 28319-77-9; 694 258.1 886 cytidine 5'-diphosphocholine LC/MS pos 34418 1.23 1.07 1.08 0.0318 0.1086 0.4588 0.4984 0.2016 0.3876 2.982317 2.425126 1.389840 1.294365 1.009338 0.936265 100 100 100 100 100 100 Lipid Glycerolipid metabolism 33818-15-4; 777 489.1 887 cytidine-5'-diphosphoethanolamine LC/MS pos 34410 C00570 HMDB01564 1.45 1.08 1.09 0.0010 0.0177 0.4558 0.4974 0.2491 0.3999 1.591711 1.095508 1.053132 0.977776 0.909007 0.836011 100 100 100 100 100 100 Lipid Glycerolipid metabolism 293 72842-05-8; 765 447 890 myo-inositol GC/MS 19934 C00137 HMDB00211 0.89 1.12 0.93 0.3185 0.3735 0.3309 0.4215 0.5391 0.5127 0.857908 0.963270 1.761572 1.571278 1.255150 1.354019 100 100 100 100 100 100 Lipid Inositol metabolism 87-89-8; 1924.9 217 891 chiro-inositol GC/MS 37112 1.00 1.00 1.02 0.7610 0.5805 0.640343 0.640343 0.640343 0.640343 0.957381 0.937083 0 0 0 0 100 100 Lipid Inositol metabolism 643-12-9; 1857 318.1 893 inositol 1-phosphate (I1P) GC/MS 1481 HMDB00213 1.00 1.02 1.27 0.9209 0.6524 0.8261 0.6662 0.0443 0.2896 1.116171 1.116083 0.809702 0.791604 0.584615 0.461213 100 100 100 100 100 100 Lipid Inositol metabolism 106032-59-1; 2057.8 318.1 898 scyllo-inositol GC/MS 32379 C06153 HMDB06088 0.75 1.18 0.82 0.2289 0.3183 0.2622 0.3883 0.4712 0.5054 0.548742 0.733003 3.467987 2.931422 1.968354 2.389041 100 100 100 100 100 100 Lipid Inositol metabolism 488-59-5; 1893.8 318.2 909 1-palmitoylglycerophosphoethanolamine LC/MS neg 35631 HMDB11503 1.13 1.00 0.89 0.9983 0.6657 0.9157 0.6829 0.5051 0.5054 0.933707 0.824861 1.018082 1.018695 1.359865 1.529136 100 100 100 100 100 100 Lipid Lysolipid 9547069 5940 452.3 910 2-palmitoylglycerophosphoethanolamine* LC/MS pos 35684 5.31 0.99 1.50 < 0.001 0.0177 0.8735 0.6727 0.6327 0.5476 1.457794 0.274795 0.306333 0.310829 1.040488 0.691950 100 75 50 50 100 100 Lipid Lysolipid 5598 454.2 911 1-palmitoleoylglycerophosphoethanolamine* LC/MS neg 34565 0.90 1.28 1.14 0.5704 0.5063 0.4760 0.4987 0.8052 0.5902 0.718285 0.796822 0.903238 0.703853 0.794831 0.694383 25 75 75 75 100 100 Lipid Lysolipid 5661 450.4 912 2-palmitoleoylglycerophosphoethanolamine* LC/MS pos 34871 1.58 0.74 1.24 0.2536 0.3392 0.7408 0.6386 0.5393 0.5127 2.331472 1.471338 0.608254 0.819158 0.667589 0.540224 100 100 100 100 100 100 Lipid Lysolipid 5487 452.1 914 1-stearoylglycerophosphoethanolamine LC/MS pos 34416 HMDB11130 1.63 0.95 0.89 0.0720 0.1621 0.9132 0.6829 0.7035 0.5648 1.167663 0.715689 0.897167 0.945434 1.538543 1.738387 100 100 100 100 100 100 Lipid Lysolipid 9547068 69747-55-3; 5842 482.3 915 1-oleoylglycerophosphoethanolamine LC/MS neg 35628 HMDB11506 1.25 1.01 0.93 0.5555 0.4984 0.9658 0.6963 0.7184 0.5704 0.507011 0.405668 0.772970 0.765197 1.328776 1.422723 100 100 100 100 100 100 Lipid Lysolipid 9547071 5928 478.3 916 2-oleoylglycerophosphoethanolamine* LC/MS neg 35687 1.14 1.13 1.18 0.5973 0.5190 0.7313 0.6327 0.4926 0.5054 0.858679 0.751537 0.977422 0.864102 1.103435 0.934515 100 100 100 100 100 100 Lipid Lysolipid 5848 478.3 918 2-linoleoylglycerophosphoethanolamine* LC/MS pos 34666 1.77 0.82 1.28 0.0233 0.0873 0.8390 0.6698 0.6882 0.5646 2.095197 1.186405 0.633843 0.768778 0.649522 0.506053 100 100 100 100 100 100 Lipid Lysolipid 5541 478.3 919 1-arachidonoylglycerophosphoethanolamine* LC/MS neg 35186 HMDB11517 1.36 1.05 1.39 0.0387 0.1153 0.7934 0.6554 0.2776 0.4301 1.478475 1.089388 0.967660 0.925636 0.567725 0.407452 100 100 100 100 100 100 Lipid Lysolipid 5731 500.3 920 2-arachidonoylglycerophosphoethanolamine* LC/MS neg 32815 1.16 1.13 1.20 0.5091 0.4781 0.4391 0.4905 0.5768 0.5346 1.591824 1.369622 1.022636 0.908748 0.645557 0.539362 100 100 100 100 100 100 Lipid Lysolipid 5674 500.3 922 2-docosapentaenoylglycerophosphoethanolamine* LC/MS pos 34875 2.28 0.80 1.29 0.0141 0.0754 0.8544 0.6727 0.6791 0.5614 3.307795 1.451410 0.747820 0.932294 0.843317 0.652930 100 100 100 100 100 100 Lipid Lysolipid 5548 528.2 923 2-docosahexaenoylglycerophosphoethanolamine* LC/MS pos 34258 1.54 0.88 1.29 0.0370 0.1144 0.9909 0.6995 0.4710 0.5054 2.614305 1.692954 1.027195 1.171996 0.997048 0.773729 100 100 100 100 100 100 Lipid Lysolipid 5512 526.2 925 1-stearoylglycerophosphoglycerol LC/MS neg 34437 1.02 1.12 1.16 0.9808 0.6620 0.9803 0.6982 0.9446 0.6261 0.465460 0.454369 0.890123 0.793035 1.335882 1.154310 75 75 75 100 100 100 Lipid Lysolipid 5826 511.4 926 1-myristoylglycerophosphocholine LC/MS pos 35626 HMDB10379 1.24 0.95 0.91 0.6496 0.5410 0.8797 0.6727 0.6920 0.5648 0.607611 0.489269 0.772916 0.811139 2.025882 2.214730 100 100 100 100 100 100 Lipid Lysolipid 460604 20559-16-4; 5481 468.3 927 2-myristoylglycerophosphocholine* LC/MS pos 35681 1.46 0.69 1.18 0.3993 0.4236 0.7458 0.6405 0.5133 0.5054 1.181529 0.810160 0.759706 1.098247 1.430702 1.207927 100 100 100 100 100 100 Lipid Lysolipid 5450 468.3 928 1-pentadecanoylglycerophosphocholine* LC/MS pos 37418 2.91 1.13 0.99 < 0.001 0.0152 0.8315 0.6666 0.7288 0.5744 1.633120 0.560264 0.791856 0.703042 0.976382 0.989129 100 100 75 75 100 100 Lipid Lysolipid 5563 482.3 929 1-palmitoylglycerophosphocholine LC/MS pos 33955 2.18 1.17 0.85 0.0245 0.0888 0.8885 0.6734 0.6455 0.5522 1.723591 0.791031 0.788097 0.670796 1.469470 1.727595 100 100 100 100 100 100 Lipid Lysolipid 86554 17364-16-8; 5671 496.4 930 2-palmitoylglycerophosphocholine* LC/MS pos 35253 3.56 0.95 1.18 0.0182 0.0803 0.9395 0.6898 0.9019 0.6156 2.898637 0.815064 0.655678 0.687590 1.016960 0.861659 100 100 100 100 100 100 Lipid Lysolipid 5604 496.3 931 1-palmitoleoylglycerophosphocholine* LC/MS pos 33230 1.54 0.80 0.85 0.1615 0.2630 0.7120 0.6274 0.5025 0.5054 0.968579 0.627986 0.685243 0.852499 1.165046 1.373957 100 100 75 100 100 100 Lipid Lysolipid 5524 494.3 932 2-palmitoleoylglycerophosphocholine* LC/MS pos 35819 1.48 0.78 1.02 0.2779 0.3586 0.8541 0.6727 0.9578 0.6281 1.523805 1.026623 0.880510 1.131201 0.790429 0.774952 100 100 100 100 100 100 Lipid Lysolipid 5482 494.3 933 1-heptadecanoylglycerophosphocholine LC/MS pos 33957 HMDB12108 1.26 0.85 0.74 0.8971 0.6471 0.6793 0.6099 0.4526 0.5054 0.889760 0.705386 0.698303 0.824651 1.148543 1.542646 50 100 100 75 100 100 Lipid Lysolipid 50930-23-9; 5750 510.4 934 1-stearoylglycerophosphocholine LC/MS pos 33961 1.38 1.02 0.90 0.2501 0.3386 0.9508 0.6906 0.6575 0.5547 0.670719 0.485184 0.820197 0.801224 1.401330 1.554764 100 100 100 100 100 100 Lipid Lysolipid 497299 19420-57-6; 5844 524.4 935 2-stearoylglycerophosphocholine* LC/MS pos 35255 2.00 1.57 1.27 0.0627 0.1505 0.5957 0.5646 0.9865 0.6353 2.373935 1.184116 0.571285 0.362898 0.768280 0.604682 100 100 75 100 100 100 Lipid Lysolipid 10208382 5780 524.4 936 1-oleoylglycerophosphocholine LC/MS pos 33960 1.81 0.96 0.72 0.0729 0.1621 0.9887 0.6995 0.4646 0.5054 1.027094 0.568058 0.660330 0.686570 1.844180 2.557002 100 100 100 100 100 100 Lipid Lysolipid 16081932 19420-56-5; 5700 522.4 937 2-oleoylglycerophosphocholine* LC/MS pos 35254 2.97 0.98 0.96 0.0100 0.0654 0.8424 0.6703 0.8662 0.6111 2.126298 0.715843 0.726455 0.741090 1.179971 1.233227 100 100 100 100 100 100 Lipid Lysolipid 5640 522.4 938 1-linoleoylglycerophosphocholine LC/MS pos 34419 C04100 2.38 0.91 0.77 0.0487 0.1282 0.7990 0.6577 0.4712 0.5054 1.361013 0.572442 0.549511 0.601396 1.796211 2.332290 100 100 75 75 100 100 Lipid Lysolipid 11988421 5574 520.4 939 2-linoleoylglycerophosphocholine* LC/MS pos 35257 1.60 0.87 0.94 0.2289 0.3183 0.9941 0.6997 0.6456 0.5522 1.915701 1.198676 0.505378 0.577890 0.872454 0.930878 100 100 100 100 100 100 Lipid Lysolipid 5544 520.4 942 1-eicosatrienoylglycerophosphocholine* LC/MS pos 33821 0.79 0.83 1.14 0.3066 0.3679 0.7197 0.6285 0.8135 0.5908 0.469458 0.593741 0.726302 0.877339 1.134723 0.993607 25 100 75 75 100 75 Lipid Lysolipid 5600 546.4 943 2-eicosatrienoylglycerophosphocholine* LC/MS pos 35884 2.87 0.80 1.03 0.0341 0.1117 0.8229 0.6659 0.7135 0.5697 2.461644 0.858534 0.648379 0.811480 0.896226 0.872380 100 100 100 100 100 100 Lipid Lysolipid 5565 546.3 945 2-arachidonoylglycerophosphocholine* LC/MS pos 35256 1.81 0.85 1.13 0.0177 0.0798 0.8968 0.6752 0.7394 0.5747 2.743804 1.517764 1.288395 1.520189 0.816464 0.725459 100 100 100 100 100 100 Lipid Lysolipid 5524 544.3 946 1-docosapentaenoylglycerophosphocholine* LC/MS pos 37231 2.72 0.93 1.03 0.0344 0.1117 0.8795 0.6727 0.9268 0.6240 1.671229 0.615211 0.753420 0.808475 0.576015 0.558692 100 100 100 75 75 100 Lipid Lysolipid 5584 570.4 947 2-docosapentaenoylglycerophosphocholine* LC/MS pos 37366 1.89 0.81 1.18 0.0374 0.1144 0.8768 0.6727 0.6293 0.5476 2.413176 1.276430 0.772652 0.951771 0.584718 0.495646 100 100 100 100 100 100 Lipid Lysolipid 5532 570.3 949 2-docosahexaenoylglycerophosphocholine* LC/MS pos 35883 1.32 0.81 1.13 0.3995 0.4236 0.8889 0.6734 0.8234 0.5933 1.956119 1.480155 0.762563 0.937934 0.635981 0.564972 100 100 100 100 100 100 Lipid Lysolipid 5507 568.3 951 1-palmitoylglycerophosphoinositol* LC/MS neg 35305 0.78 1.33 1.15 0.1699 0.2677 0.0680 0.3048 0.4414 0.5054 2.596489 3.345646 0.949310 0.714639 0.956401 0.832220 100 100 100 100 100 100 Lipid Lysolipid 5573 571.3 954 1-stearoylglycerophosphoinositol LC/MS neg 19324 0.99 1.31 1.24 0.8549 0.6353 0.2023 0.3472 0.2360 0.3991 1.361478 1.380424 1.059502 0.808976 1.098613 0.883523 100 100 100 100 100 100 Lipid Lysolipid 5800 599.4 956 1-oleoylglycerophosphoinositol* LC/MS neg 36602 0.86 1.05 1.05 0.5494 0.4969 0.9575 0.6924 0.7656 0.5808 0.832165 0.972263 0.607938 0.579634 1.495665 1.418096 100 100 75 100 100 100 Lipid Lysolipid 5577 597.4 959 1-arachidonoylglycerophosphoinositol* LC/MS neg 34214 1.40 0.96 1.15 0.1093 0.1961 0.7108 0.6274 0.0875 0.3258 1.545732 1.101806 0.765427 0.799754 0.425566 0.369754 100 100 75 100 100 100 Lipid Lysolipid 5479 619.4 960 2-arachidonoylglycerophosphoinositol* LC/MS neg 38077 0.62 1.47 1.04 0.3982 0.4236 0.2810 0.3883 0.8059 0.5902 0.774110 1.248616 1.456433 0.990538 1.031873 0.990997 75 75 100 100 100 100 Lipid Lysolipid 5456 619.3 961 2-oleoylglycerophosphoinositol* LC/MS neg 37232 0.64 3.52 1.80 0.8900 0.6440 0.8760 0.6727 0.5278 0.5127 0.877621 1.371489 0.954855 0.270967 0.214834 0.119099 100 100 50 100 50 50 Lipid Lysolipid 5571 597.5 962 1-oleoylglycerophosphoserine LC/MS neg 19260 1.24 1.21 1.17 0.3375 0.3855 0.2330 0.3704 0.3762 0.4872 1.429700 1.156229 0.857332 0.710398 0.774978 0.660353 100 100 100 100 100 100 Lipid Lysolipid 9547099 5690 522.3 963 2-oleoylglycerophosphoserine* LC/MS neg 37948 0.81 0.96 1.30 0.5166 0.4791 0.7892 0.6554 0.1798 0.3681 0.893281 1.102906 0.860605 0.894453 1.084553 0.835351 75 100 100 100 100 100 Lipid Lysolipid 5577 522.3 964 1-palmitoylplasmenylethanolamine* LC/MS neg 39270 1.34 1.13 0.92 0.5283 0.4858 0.7061 0.6270 0.8065 0.5902 1.872608 1.394777 0.797605 0.707277 1.200313 1.307446 100 100 100 100 100 100 Lipid Lysolipid 6153 436.4 970 1-palmitoylglycerol (1-monopalmitin) GC/MS 21127 1.03 1.38 1.06 0.7992 0.6025 0.3035 0.4043 0.6542 0.5547 1.086332 1.058778 0.977661 0.708619 0.721714 0.682951 100 100 100 100 100 100 Lipid Monoacylglycerol 14900 542-44-9; 2119.5 371.3 971 2-palmitoylglycerol (2-monopalmitin) GC/MS 33419 1.26 1.24 0.76 0.1355 0.2319 0.2539 0.3872 0.1764 0.3681 1.545505 1.226067 0.579910 0.468544 0.458342 0.600553 100 100 100 75 50 75 Lipid Monoacylglycerol 123409 23470-00-0; 2108 129 972 1-stearoylglycerol (1-monostearin) GC/MS 21188 D01947 1.26 1.21 1.11 0.1003 0.1845 0.2850 0.3896 0.5029 0.5054 1.075592 0.856614 1.183975 0.982328 0.867130 0.778473 100 100 100 100 100 100 Lipid Monoacylglycerol 24699 123-94-4; 2186.6 399.4 974 1-oleoylglycerol (1-monoolein) GC/MS 21184 HMDB11567 1.16 1.46 1.02 0.5851 0.5134 0.1948 0.3472 0.8877 0.6156 1.102655 0.950592 1.263262 0.863643 1.217151 1.192385 100 100 100 100 100 100 Lipid Monoacylglycerol 5283468 111-03-5; 2181.2 397.4 975 2-oleoylglycerol (2-monoolein) GC/MS 35848 1.22 3.20 0.97 0.9145 0.6524 0.1922 0.3472 0.7776 0.5822 1.408796 1.152205 0.417688 0.130501 0.471073 0.483683 75 75 50 50 50 75 Lipid Monoacylglycerol 5319879 3443-84-3; 2170 410.1 990 Diacylglycerol 1,3-dipalmitoylglycerol GC/MS 35728 0.95 1.23 1.30 0.7972 0.6025 0.3531 0.4330 0.1653 0.3681 1.082519 1.142940 1.043585 0.850623 0.852802 0.655696 100 100 100 100 100 100 Lipid Diacylglycerol 68149 26657-95-4 ; 2637 371.3 993 sphinganine LC/MS pos 17769 C00836 HMDB00269 1.21 1.06 1.16 0.4491 0.4526 0.7621 0.6508 0.2559 0.4056 0.938264 0.775925 0.936962 0.886485 1.077111 0.929293 100 100 100 100 100 100 Lipid Sphingolipid 3126 3102-56-5; 5175 302.3 995 sphingosine LC/MS pos 17747 C00319 HMDB00252 1.25 1.05 1.10 0.3732 0.4118 0.7212 0.6285 0.5391 0.5127 2.123859 1.697609 0.596619 0.569378 0.913292 0.831667 100 100 100 100 100 100 Lipid Sphingolipid 5353955 123-78-4; 5197 300.2 1004 palmitoyl sphingomyelin GC/MS 37506 1.00 1.29 1.31 0.9783 0.6620 0.0799 0.3048 0.0110 0.2697 1.260049 1.265073 0.940634 0.729649 0.304433 0.231686 100 100 100 100 100 100 Lipid Sphingolipid 9939941 2524 311.3 1005 stearoyl sphingomyelin GC/MS 19503 C00550 HMDB01348 1.51 1.46 1.24 0.1184 0.2090 0.0322 0.3048 0.1677 0.3681 0.857708 0.567919 1.472753 1.006015 0.459907 0.370894 100 100 100 100 100 100 Lipid Sphingolipid 6453725 85187-10-6;85187-10-6 ; 2645 311.3 1018 lathosterol GC/MS 33488 C01189 HMDB01170 0.93 1.15 1.37 0.7263 0.5808 0.5445 0.5430 0.0138 0.2896 0.644216 0.690371 1.146110 0.994000 1.005574 0.733957 100 100 100 100 100 100 Lipid Sterol/Steroid 65728 80-99-9 ; 2337 458.5 1020 cholesterol GC/MS 63 C00187 HMDB00067 0.97 1.20 1.12 0.6158 0.5215 0.2258 0.3680 0.1182 0.3533 0.707315 0.727125 1.042030 0.870295 0.563599 0.501009 100 100 100 100 100 100 Lipid Sterol/Steroid 6432564 57-88-5; 2316.9 329.3 1021 7-dehydrocholesterol GC/MS 40398 C01164 HMDB00032 1.40 1.40 1.26 0.0567 0.1407 0.0298 0.3048 0.0828 0.3258 2.503665 1.789075 0.347624 0.248277 1.191959 0.946501 100 100 100 100 100 100 Lipid Sterol/Steroid 439423 434-16-2; 2330.5 325.3 1023 7-alpha-hydroxycholesterol GC/MS 35692 C03594 HMDB01496 0.84 1.20 1.14 0.3912 0.4236 0.1730 0.3353 0.4416 0.5054 0.871197 1.032599 1.245222 1.035293 0.717838 0.628668 100 100 100 100 100 75 Lipid Sterol/Steroid 107722 566-27-8; 2300 456.2 1024 7-beta-hydroxycholesterol GC/MS 35092 C03594 HMDB06119 0.86 1.48 1.03 0.3966 0.4236 0.1289 0.3048 0.7625 0.5805 0.840644 0.978501 1.095959 0.742182 0.488818 0.473519 100 100 100 100 100 100 Lipid Sterol/Steroid 473141 566-27-8; 2340 456.4 1095 xanthine GC/MS 3147 C00385 HMDB00292 0.98 0.87 1.35 0.9284 0.6525 0.6663 0.6039 0.3274 0.4590 1.032902 1.055028 1.311044 1.502072 0.646455 0.479435 100 100 50 75 100 75 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 1188 69-89-6; 1889.9 353 1096 xanthosine LC/MS pos 15136 C01762 HMDB00299 1.00 1.63 1.17 0.1026 0.3048 0.3947 0.4872 0.164405 0.164405 0.452017 0.277371 1.175029 1.001718 0 0 100 75 100 100 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 64959 146-80-5; 1785 285 1097 xanthosine 5'-monophosphate (xmp) LC/MS pos 12024 C00655 HMDB01554 1.18 1.09 1.73 0.6069 0.5215 0.9849 0.6994 0.2174 0.3984 0.517420 0.440035 0.901445 0.828627 4.916435 2.836047 75 100 75 100 100 100 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 25899-70-1; 1421 365 1098 hypoxanthine LC/MS neg 3127 C00262 HMDB00157 1.13 1.25 1.09 0.0777 0.1621 0.1089 0.3048 0.4088 0.4896 0.931230 0.821087 1.601585 1.277772 1.301740 1.193486 100 100 100 100 100 100 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 790 68-94-0; 1313 135.1 1099 inosine LC/MS neg 1123 1.38 1.36 1.16 0.0069 0.0560 0.0559 0.3048 0.2298 0.3984 1.141634 0.826648 1.763230 1.300101 1.203708 1.038360 100 100 100 100 100 100 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 58-63-9; 1630 267.2 1100 2'-deoxyinosine LC/MS neg 15076 C05512 HMDB00071 1.13 1.28 0.87 0.2969 0.3679 0.0576 0.3048 0.0907 0.3258 0.551283 0.488661 0.904503 0.708230 1.140737 1.308565 100 100 100 100 100 100 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 65058 890-38-0; 1700 251.1 1101 inosine 5'-monophosphate (IMP) LC/MS pos 2133 C00130 HMDB00175 1.07 1.22 1.07 0.6236 0.5233 0.1253 0.3048 0.5976 0.5403 1.031694 0.965543 2.190594 1.802019 0.722477 0.674631 100 100 100 100 100 100 Nucleotide Purine metabolism, (hypo)xanthine/inosine containing 7140378 4691-65-0; 1310 349 1105 adenine LC/MS pos 554 C00147 HMDB00034 1.04 1.27 1.38 0.9200 0.6524 0.0233 0.3048 0.0020 0.1339 0.281636 0.270298 1.127292 0.885730 0.731935 0.528730 75 100 100 100 100 100 Nucleotide Purine metabolism, adenine containing 190 73-24-5; 1003 136.1 1106 adenosine LC/MS pos 555 C00212 HMDB00050 1.24 1.19 1.50 0.0462 0.1258 0.5162 0.5270 0.0459 0.2896 1.020050 0.822349 0.807921 0.677184 0.901501 0.599791 100 100 100 100 100 100 Nucleotide Purine metabolism, adenine containing 60961 58-61-7; 1650 268.1 1108 N1-methyladenosine LC/MS pos 15650 C02494 HMDB03331 1.22 1.11 0.94 0.0870 0.1669 0.4534 0.4974 0.4669 0.5054 1.561766 1.277889 0.725071 0.650705 0.553065 0.589713 100 100 100 100 100 100 Nucleotide Purine metabolism, adenine containing 5460178 15763-06-1; 1356 282.1 1109 N6-methyladenosine LC/MS pos 37114 HMDB04044 1.00 1.12 1.16 0.3910 0.4533 0.3424 0.4653 0.669701 0.669701 0.752276 0.669701 0.907167 0.780415 0 0 25 0 75 75 Nucleotide Purine metabolism, adenine containing 102175 1867-73-8; 1985 282.1 1110 2'-deoxyadenosine LC/MS pos 1553 C00559 HMDB00101 1.00 1.00 1.00 0.099339 0.099339 0.099339 0.099339 0.099339 0.099339 0 0 0 0 0 0 Nucleotide Purine metabolism, adenine containing 13730 16373-93-6; 1632 252.1 1112 adenosine 2'-monophosphate (2'-AMP) LC/MS pos 36815 C00946 HMDB11617 1.19 1.37 0.64 0.4057 0.4243 0.0677 0.3048 0.1153 0.3533 1.039461 0.871459 1.336395 0.977656 0.240891 0.375485 100 100 100 100 75 100 Nucleotide Purine metabolism, adenine containing 130-49-4; 1625 348.1 1113 adenosine 3'-monophosphate (3'-AMP) LC/MS pos 35142 C01367 HMDB03540 1.02 1.46 1.00 0.9336 0.6541 0.4909 0.5078 1.089048 1.072606 0.376072 0.257737 0.163235 0.163235 100 100 75 100 0 0 Nucleotide Purine metabolism, adenine containing 15938966 84-21-9; 1451 348.1 1114 adenosine 5'-monophosphate (AMP) LC/MS pos 32342 C00020 HMDB00045 1.17 1.16 0.98 0.0478 0.1282 0.2783 0.3883 0.8299 0.5933 1.254745 1.073911 1.026836 0.884188 0.873196 0.886654 100 100 100 100 100 100 Nucleotide Purine metabolism, adenine containing 15938965 149022-20-8; 1210 348.1 1116 adenosine 5'-diphosphate (ADP) LC/MS pos 3108 C00008 HMDB01341 1.03 0.89 0.91 0.9506 0.6554 0.4498 0.4974 0.4927 0.5054 3.147582 3.055791 0.379452 0.424205 0.954650 1.049412 100 100 75 100 100 100 Nucleotide Purine metabolism, adenine containing 6022 20398-34-9; 1005 428 1122 adenylosuccinate LC/MS pos 18360 C03794 HMDB00536 0.63 1.56 1.11 0.0749 0.1621 0.0912 0.3048 0.9839 0.6353 1.033004 1.646571 0.835805 0.537103 1.668195 1.506075 100 100 100 100 100 100 Nucleotide Purine metabolism, adenine containing 195 19046-78-7; 1870 464.1 1124 guanine LC/MS pos 32352 C00242 HMDB00132 1.33 1.28 1.20 0.0807 0.1633 0.0562 0.3048 0.1265 0.3533 0.679103 0.510221 1.132163 0.881754 0.768152 0.639484 100 100 100 100 100 100 Nucleotide Purine metabolism, guanine containing 764 73-40-5; 1022 152.1 1128 guanosine LC/MS neg 1573 C00387 HMDB00133 1.27 1.48 1.20 0.0433 0.1241 0.0165 0.3048 0.0912 0.3258 0.878885 0.692677 1.696551 1.143470 1.048391 0.875090 100 100 100 100 100 100 Nucleotide Purine metabolism, guanine containing 6802 118-00-3; 1675 282.1 1129 2'-deoxyguanosine LC/MS neg 1411 C00330 HMDB00085 1.00 1.16 0.82 0.3910 0.4533 0.1727 0.3681 0.369615 0.369615 0.429967 0.369615 0.753345 0.916733 0 0 25 25 100 100 Nucleotide Purine metabolism, guanine containing 187790 961-07-9; 1759 266.2 1131 guanosine 5'- monophosphate (5'-GMP) LC/MS pos 2849 1.16 1.09 1.12 0.0793 0.1621 0.4722 0.4987 0.4163 0.4939 1.159391 0.995898 0.909555 0.833100 0.660695 0.591373 100 100 100 100 100 100 Nucleotide Purine metabolism, guanine containing 761 5550-12-9; 1300 364 1137 guanosine 5'-diphospho-fucose LC/MS neg 15903 1.33 1.26 1.12 0.0326 0.1089 0.1451 0.3168 0.2563 0.4056 1.415168 1.060566 1.204339 0.956338 0.779051 0.693972 100 100 100 100 100 100 Nucleotide Purine metabolism, guanine containing 15839-70-0; 797 588.1 1140 N1-methylguanosine LC/MS pos 31609 HMDB01563 0.89 1.58 1.28 0.5655 0.5053 0.0833 0.3048 0.2824 0.4345 1.140723 1.282121 0.864645 0.546399 0.917636 0.717178 75 100 100 100 100 100 Nucleotide Purine metabolism, guanine containing 96373 2140-65-0; 1850 298.1 1141 N2-methylguanosine LC/MS pos 35133 HMDB05862 0.54 0.68 1.32 0.0825 0.1633 0.2077 0.3481 0.0872 0.3258 0.550970 1.023026 0.310325 0.455151 0.838543 0.637476 50 100 0 75 100 100 Nucleotide Purine metabolism, guanine containing 3035422 2140-77-4; 1950 298.1 1145 N6-carbamoylthreonyladenosine LC/MS pos 35157 0.83 1.05 0.81 0.0503 0.1282 0.6271 0.5805 0.1321 0.3533 1.031095 1.240880 0.551197 0.522809 0.916662 1.133645 100 100 100 100 100 100 Nucleotide Purine metabolism, guanine containing 24719-82-2; 2656 413 1149 urate GC/MS 1604 C00366 HMDB00289 0.98 0.75 1.40 0.9693 0.6582 0.6028 0.5691 0.3597 0.4759 0.395372 0.404404 0.919777 1.224806 1.680970 1.204303 100 100 50 75 100 75 Nucleotide Purine metabolism, urate metabolism 69-93-2;120K5305; 1928 441.2 1150 allantoin GC/MS 1107 C02350 HMDB00462 0.96 0.99 1.37 0.7208 0.5808 0.8661 0.6727 0.1529 0.3681 1.189373 1.244184 0.988218 1.000553 0.786048 0.572253 100 100 100 100 100 100 Nucleotide Purine metabolism, urate metabolism 204 97-59-6; 1809.8 518.3 1153 cytidine LC/MS pos 514 C00475 HMDB00089 1.34 1.27 0.94 0.0101 0.0654 0.0841 0.3048 0.3882 0.4872 1.108344 0.824516 2.017108 1.592042 1.412321 1.497309 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, cytidine containing 6175 65-46-3; 1065 244 1157 cytidine 5'-monophosphate (5'-CMP) LC/MS pos 2372 C00055 HMDB00095 1.43 1.20 1.06 < 0.001 0.0177 0.1787 0.3429 0.4861 0.5054 1.283989 0.897649 0.736396 0.612531 0.911012 0.860730 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, cytidine containing 7058165 63-37-6; 887 324 1162 2'-deoxycytidine LC/MS pos 15949 C00881 HMDB00014 0.91 1.84 0.91 0.5162 0.4791 0.0179 0.3048 0.4992 0.5054 0.911631 0.999177 1.263792 0.687116 0.854399 0.937266 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, cytidine containing 13711 951-77-9; 1256 228 1164 cytosine GC/MS 573 C00380 HMDB00630 1.46 1.52 0.89 0.9647 0.6582 0.2992 0.4043 0.6964 0.5648 1.409295 0.968349 1.192844 0.782829 0.806732 0.911451 50 100 100 100 100 100 Nucleotide Pyrimidine metabolism, cytidine containing 597 71-30-7; 1535.5 254 1168 Pyrimidine metabolism, orotate containing orotate GC/MS 1505 C00295 HMDB00226 0.44 0.89 1.09 0.0121 0.0704 0.6677 0.6039 0.6034 0.5433 0.032328 0.073938 0.854006 0.959542 2.474694 2.277906 50 100 100 100 100 100 Nucleotide Pyrimidine metabolism, orotate containing 967 50887-69-9; 1709.6 254.1 1172 thymine GC/MS 604 C00178 HMDB00262 0.86 1.15 1.00 0.2913 0.3674 0.1717 0.3353 0.8698 0.6117 0.832771 0.963338 2.687885 2.331095 0.878215 0.874126 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, thymine containing 1135 65-71-4; 1429.1 255 1173 thymidine LC/MS neg 39539 C00214 HMDB00273 1.00 1.15 0.94 0.4287 0.4867 0.5031 0.5054 0.510446 0.510446 0.886887 0.771244 0.969145 1.031366 0 0 100 100 100 100 Nucleotide Pyrimidine metabolism, thymine containing 5789 50-89-5; 1935 284.8 1175 thymidine 5'-monophosphate LC/MS neg 12023 C00364 HMDB01227 0.93 1.15 0.94 0.4339 0.4434 0.2653 0.3883 0.3554 0.4743 0.565036 0.610820 1.097620 0.956714 1.867250 1.994531 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, thymine containing 33430-62-5; 924 321.1 1178 uracil GC/MS 605 C00106 HMDB00300 0.94 1.23 0.90 0.6473 0.5410 0.0755 0.3048 0.3449 0.4659 0.151405 0.161419 2.051402 1.663628 1.101143 1.217132 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, uracil containing 1174 66-22-8; 1370.4 241 1180 uridine LC/MS neg 606 C00299 HMDB00296 1.38 1.31 1.02 0.0358 0.1144 0.1097 0.3048 0.8278 0.5933 0.776843 0.564204 1.113038 0.847523 1.211799 1.185497 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, uracil containing 6029 58-96-8; 1467 243.1 1181 pseudouridine LC/MS neg 33442 C02067 HMDB00767 1.13 1.08 0.92 0.3171 0.3735 0.5622 0.5459 0.4078 0.4896 1.109569 0.984975 0.903936 0.833889 0.742416 0.803954 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, uracil containing 1445-07-4; 1104 243.1 1183 5-methyluridine (ribothymidine) LC/MS neg 35136 HMDB00884 1.00 1.54 1.25 0.0114 0.3048 0.0193 0.2896 0.629414 0.629414 1.309229 0.851311 1.025632 0.817660 0 0 100 100 100 100 Nucleotide Pyrimidine metabolism, uracil containing 445408 1463-10-1; 1774 257.1 1187 uridine monophosphate (5' or 3') LC/MS neg 39892 1.52 1.15 1.01 0.0013 0.0203 0.3616 0.4382 0.8060 0.5902 1.637642 1.074056 0.747321 0.650420 0.705439 0.695194 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, uracil containing 635 323.1 1189 uridine 5'-diphosphate (UDP) LC/MS pos 5345 C00015 HMDB00295 1.57 1.16 0.94 0.1393 0.2345 0.4557 0.4974 0.5814 0.5366 1.200464 0.765384 0.963774 0.830723 1.080083 1.152559 100 100 100 100 100 100 Nucleotide Pyrimidine metabolism, uracil containing 6031 21931-53-3; 862 405 1193 Purine and pyrimidine metabolism methylphosphate GC/MS 37070 1.11 1.20 1.49 0.5862 0.5134 0.2058 0.3472 0.0392 0.2896 0.820160 0.739495 1.369978 1.138574 0.888105 0.594468 100 100 100 100 100 100 Nucleotide Purine and pyrimidine metabolism 13130 7023-27-0; 1221 240.9 1196 Ascorbate and aldarate metabolism gulono-1,4-lactone GC/MS 33454 C01040 HMDB03466 0.62 1.27 0.86 0.1217 0.2131 0.0926 0.3048 0.2286 0.3984 1.166276 1.868762 1.813585 1.424075 0.823047 0.955152 100 100 100 100 100 100 Cofactors and vitamins Ascorbate and aldarate metabolism 608 1128-23-0; 1862 333.1 1204 Biotin metabolism biotin LC/MS pos 568 C00120 HMDB00030 1.29 1.07 1.07 0.0119 0.0704 0.6106 0.5719 0.4557 0.5054 1.091431 0.846496 0.834629 0.783093 0.977743 0.915379 100 100 100 100 100 100 Cofactors and vitamins Biotin metabolism 171548 58-85-5; 3029 245.2 1206 Folate metabolism 5-methyltetrahydrofolate (5MeTHF) LC/MS neg 18330 C00440 HMDB01396 0.97 1.02 0.68 0.7354 0.5816 0.8064 0.6615 0.0106 0.2697 1.125017 1.154823 0.666121 0.650642 0.883110 1.300911 100 100 100 100 100 100 Cofactors and vitamins Folate metabolism 146 68703-91-3;68792-52-9; 1838 458.2 1212 Hemoglobin and porphyrin metabolism heme* LC/MS pos 32593 1.00 0.95 1.35 0.8736 0.6727 0.2081 0.3939 0.291963 0.291963 1.746218 1.829162 0.485623 0.359788 0 0 100 100 100 100 Cofactors and vitamins Hemoglobin and porphyrin metabolism 14875-96-8; 4985 616.2 1221 nicotinamide LC/MS pos 594 C00153 HMDB01406 0.99 1.27 1.10 0.9385 0.6554 0.2605 0.3883 0.4360 0.5054 0.524327 0.530799 1.500928 1.177693 1.158115 1.052085 100 100 100 100 100 100 Cofactors and vitamins Nicotinate and nicotinamide metabolism 936 98-92-0; 1267 123.1 1224 nicotinamide adenine dinucleotide (NAD+) LC/MS pos 5278 C00003 HMDB00902 0.91 1.26 1.12 0.4704 0.4594 0.0790 0.3048 0.4003 0.4872 0.761619 0.834714 0.978877 0.777848 18.295730 16.346530 100 100 100 100 100 100 Cofactors and vitamins Nicotinate and nicotinamide metabolism ###################### 53-84-9; 1370 664 1225 nicotinamide adenine dinucleotide reduced (NADH) LC/MS neg 31475 C00004 HMDB01487 1.66 1.18 1.00 0.1930 0.2933 0.3647 0.4382 0.8483 0.6023 0.704193 0.424619 0.853997 0.724929 6.073659 6.050848 50 50 100 100 100 100 Cofactors and vitamins Nicotinate and nicotinamide metabolism 439153 58-68-4 ;606-68-8; 1554 664.1 1231 nicotinamide riboside* LC/MS pos 33013 3.38 1.27 0.56 0.0945 0.1767 0.2278 0.3687 0.0596 0.2896 0.761636 0.225318 1.205517 0.948681 0.313848 0.562909 75 50 100 100 75 100 Cofactors and vitamins Nicotinate and nicotinamide metabolism 1341-23-7; 955 255.1 1232 adenosine 5'diphosphoribose LC/MS neg 558 C00301 HMDB01178 1.00 1.68 1.00 0.3602 0.4382 0.167345 0.167345 0.339419 0.202397 0.167345 0.167345 0 0 75 50 0 0 Cofactors and vitamins Nicotinate and nicotinamide metabolism 4475880 68414-18-6; 964 558.1 1235 nicotinate LC/MS neg 1504 C00253 HMDB01488 1.00 1.00 1.00 0.110037 0.110037 0.110037 0.110037 0.110037 0.110037 0 0 0 0 0 0 Cofactors and vitamins Nicotinate and nicotinamide metabolism 938 59-67-6; 1221 122.1 1243 pantothenate LC/MS pos 1508 C00864 HMDB00210 1.20 1.27 1.03 0.0211 0.0841 0.0749 0.3048 0.6259 0.5476 1.395356 1.164787 1.482478 1.170283 1.052185 1.018982 100 100 100 100 100 100 Cofactors and vitamins Pantothenate and CoA metabolism 6613 137-08-6; 2218 220.1 1244 phosphopantetheine LC/MS pos 15504 C01134 HMDB01416 1.77 1.43 1.28 0.0439 0.1243 0.0309 0.3048 0.0851 0.3258 1.174225 0.664506 3.261927 2.279123 0.926164 0.720943 100 100 100 100 100 100 Cofactors and vitamins Pantothenate and CoA metabolism 115254 NA; 2323 359.1 1245 coenzyme A LC/MS neg 2936 C00010 HMDB01423 1.31 1.10 0.95 0.0154 0.0754 0.5280 0.5345 0.5428 0.5139 1.282725 0.978241 0.654230 0.594328 1.286783 1.357368 100 100 100 100 100 100 Cofactors and vitamins Pantothenate and CoA metabolism 317 85-61-0;18439-24-2; 1600 766.1 1246 3'-dephosphocoenzyme A LC/MS neg 18289 C00882 HMDB01373 1.46 1.20 0.89 0.0791 0.1621 0.2043 0.3472 0.2490 0.3999 2.334406 1.602370 1.006155 0.839712 0.782647 0.879435 100 100 100 100 100 100 Cofactors and vitamins Pantothenate and CoA metabolism 444485 3633-59-8; 2010 686.2 1258 Pyridoxal metabolism pyridoxal LC/MS neg 1651 C00250 HMDB01545 1.24 1.30 0.99 0.3258 0.3765 0.1236 0.3048 0.9346 0.6255 1.349401 1.091195 1.290209 0.990157 0.730966 0.737652 100 100 100 100 100 100 Cofactors and vitamins Pyridoxal metabolism 1050 65-22-5; 1570 166.1 1259 flavin adenine dinucleotide (FAD) LC/MS neg 2134 C00016 HMDB01248 1.02 1.20 1.03 0.8261 0.6160 0.1093 0.3048 0.5564 0.5203 1.115138 1.090666 1.031898 0.862785 0.701224 0.681905 100 100 100 100 100 100 Cofactors and vitamins Riboflavin metabolism 643975 146-14-5;84366-81-4; 2413 784.1 1260 riboflavin (Vitamin B2) LC/MS pos 1827 C00255 HMDB00244 1.07 1.24 1.09 0.6114 0.5215 0.0743 0.3048 0.4375 0.5054 1.169364 1.097420 0.942275 0.758312 0.719392 0.658654 100 100 100 100 100 100 Cofactors and vitamins Riboflavin metabolism 493570 83-88-5; 3111 377.2 1262 Thiamine metabolism thiamin (Vitamin B1) LC/MS pos 5341 0.90 1.37 0.92 0.4544 0.4536 0.0648 0.3048 0.4747 0.5054 0.512108 0.566658 0.931958 0.678993 1.116728 1.211545 100 100 100 100 100 100 Cofactors and vitamins Thiamine metabolism 59-43-8; 740 265.1 1266 Tocopherol metabolism alpha-tocopherol GC/MS 1561 C02477 HMDB01893 1.32 1.27 0.96 0.0651 0.1529 0.2529 0.3872 0.7814 0.5828 0.731242 0.552350 1.230660 0.969103 0.725560 0.758922 100 100 100 100 100 100 Cofactors and vitamins Tocopherol metabolism 14985 59-02-9;10191-41-0; 2305.4 502.5 1282 pyridoxate LC/MS neg 31555 C00847 HMDB00017 0.52 1.25 1.21 0.0779 0.1621 0.3714 0.4417 0.3157 0.4562 0.346252 0.671120 1.248475 1.001168 0.559798 0.464555 0 75 100 100 100 100 Cofactors and vitamins Vitamin B6 metabolism 6723 82-82-6 ; 2210 182.1 1284 pyridoxine (Vitamin B6) LC/MS neg 608 C00314 HMDB02075 0.96 1.41 0.96 0.7971 0.6025 0.1936 0.3472 0.9389 0.6261 0.875150 0.910272 1.128335 0.800710 0.927671 0.962711 100 100 100 100 100 100 Cofactors and vitamins Vitamin B6 metabolism 1054 58-56-0; 1675 168.1 1288 hippurate LC/MS neg 15753 C01586 HMDB00714 1.22 1.24 1.08 0.1040 0.1881 0.3042 0.4043 0.2661 0.4181 1.391244 1.144716 0.611306 0.491731 0.480922 0.444646 100 100 100 100 100 100 Xenobiotics Benzoate metabolism 464 495-69-2; 2136 178.1 1297 4-hydroxymandelate GC/MS 1568 C03198 HMDB00822 1.00 1.00 1.29 0.0413 0.2896 0.669440 0.669440 0.669440 0.669440 1.104324 0.854892 0 0 0 0 100 100 Xenobiotics Benzoate metabolism 328 7198-10-9;184901-84-6; 1735.5 267.1 1324 glycerol 2-phosphate GC/MS 27728 C02979,D01 488 HMDB02520 1.61 1.27 1.13 0.0071 0.0560 0.1223 0.3048 0.4790 0.5054 1.791426 1.109852 0.663928 0.523111 0.690366 0.609107 100 100 100 100 100 100 Xenobiotics Chemical 2526 819-83-0; 1691.8 243 1341 HEPES LC/MS neg 21248 1.00 1.11 0.85 0.9252 0.6524 0.3482 0.4292 0.0186 0.2896 1.189375 1.193151 0.881524 0.795889 0.737928 0.866749 100 100 100 100 100 100 Xenobiotics Chemical 32 758 842 383 123 800 7365-45-9; 1033 237.2 1360 Isobar: 2-propylpentanoate, 2-ethylhexanoate LC/MS neg 35490 1.08 1.08 1.32 0.3983 0.4236 0.5850 0.5635 0.0459 0.2896 1.045713 0.969088 0.838549 0.774749 0.720834 0.544220 100 100 100 100 100 100 Xenobiotics Chemical 3909 143.1 1376 phenol red LC/MS neg 36817 C12600 0.79 1.09 1.19 0.0195 0.0819 0.5939 0.5646 0.1784 0.3681 0.568071 0.716394 1.047070 0.963431 0.399504 0.334322 100 100 100 100 100 100 Xenobiotics Chemical 4766 143-74-8; 3650 353.1 1455 amphotericin B LC/MS neg 31703 C06573 1.26 1.19 1.40 0.8008 0.6025 0.3916 0.4533 0.0383 0.2896 6.327631 5.010481 1.273517 1.067247 0.582476 0.416929 100 100 100 100 100 100 Xenobiotics Drug 1397-89-3 ; 5185 922.2 1462 penicillin G LC/MS pos 37468 C05551 0.34 1.36 1.00 < 0.001 0.0177 0.1938 0.3472 3.458333 10.186000 0.765851 0.562890 0.143975 0.143975 100 100 100 100 0 0 Xenobiotics Drug 2349 69-57-8; 3314 335.2 1492 doxycycline LC/MS neg 39273 0.40 1.00 1.00 0.0836 0.1633 0.440960 1.103758 0.440960 0.440960 0.440960 0.440960 0 100 0 0 0 0 Xenobiotics Drug 24390-14-5; 3768.2 443.2 1509 daidzein LC/MS neg 32453 C10208 HMDB03312 1.00 1.00 1.13 0.1847 0.3687 0.730162 0.730162 0.730162 0.730162 0.973190 0.863232 0 0 0 0 100 100 Xenobiotics Food component/plant 5281708 486-66-8 ; 3541 253.1 1585 homostachydrine* LC/MS pos 33009 C08283 1.29 1.20 1.20 0.0505 0.1282 0.1083 0.3048 0.2442 0.3999 1.147983 0.887128 1.195665 0.997091 0.419111 0.349590 100 100 100 100 100 100 Xenobiotics Food component/plant 441447 1195-94-4; 1199 158.2 1632 Sugar, sugar substitute, starch erythritol GC/MS 20699 C00503 HMDB02994 0.91 1.14 1.07 0.3336 0.3835 0.3134 0.4119 0.3372 0.4653 1.128268 1.233186 1.328356 1.170317 0.875539 0.820213 100 100 100 100 100 100 Xenobiotics Sugar, sugar substitute, starch 149-32-6; 1517.5 217 Endocannabinoid Fatty acid metabolism (also BCAA metabolism) Carnitine metabolism Bile acid metabolism Glycerolipid metabolism Inositol metabolism Lipid Long chain fatty acid Fatty acid, monohydroxy Fatty acid, dicarboxylate Fatty acid, amide Lysolipid Monoacylglycerol Sphingolipid Sterol/Steroid Nucleotide Purine metabolism, (hypo)xanthine/inosine containing Purine metabolism, adenine containing Purine metabolism, guanine containing Purine metabolism, urate metabolism Pyrimidine metabolism, cytidine containing Xenobiotics Benzoate metabolism Chemical Drug Food component/plant Pyrimidine metabolism, thymine containing Pyrimidine metabolism, uracil containing Cofactors and vitamins Nicotinate and nicotinamide metabolism Pantothenate and CoA metabolism Riboflavin metabolism Vitamin B6 metabolism

Table S6: Putative mir-125b target transcripts encoding key enzymes and regulators of metabolism Gene symbol Encoded factor Main role(s) Glycolysis HK2 Hexokinase 2 Glucose -> Glucose-6P (first step of glycolysis) Tricarboxylic acids cycle PDK1 PDK2 PDK3 SLC25A10 / DIC Lipid synthesis Pyruvate dehydrogenase kinase, isozyme 1 Pyruvate dehydrogenase kinase, isozyme 2 Pyruvate dehydrogenase kinase, isozyme 3 Solute carrier family 25 (mitochondrial carrier; dicarboxylate transporter), member 10 Phosphorylates the pyruvate dehydrogenase complex, impairing the oxidative decarboxylation of pyruvate Same as PDK1 Same as PDK1 Transport of dicarboxylates such as malate and succinate across the mitochondrial membranes / Supplying substrates for the TCA cycle, gluconeogenesis, urea synthesis, and sulfur metabolism FADS3 Fatty acid desaturase 3 Regulates unsaturation of fatty acids through introduction of double bonds between defined carbons of the fatty acyl chain SLC27A1 / FATP1 Solute carrier family 27 (fatty acid transporter), member 1 Balances storage with metabolic needs during transitions between fasted and fed states ELOVL6 Fatty acid elongase 6 Uses malonyl-coa as a 2- carbon donor in the first and rate-limiting step of fatty acid Metabolic changes compatible with increased activity in CLL patients with lower mir-125b levels Significant lower levels of glucose and glucose-6-phosphate indicative of increased glucose utilisation ( Warburg effect ) Lower citrate levels consistent with limited entry of glycolytic end products into the TCA cycle Same as PDK1 Same as PDK1 Higher levels of succinate, fumarate and malate, suggesting anaplerotic incorporation of amino acids into the TCA cycle for energy production Higher levels of essential, mediumand long-chain fatty acids, as well as of monoacylglycerols and glycerol, suggesting increased lipolysis to support fatty acid synthesis and membrane remodeling

SCD / SCD1 Glutaminolysis Stearoyl-Coenzyme A desaturase 1 elongation Catalyzes a rate-limiting step in the synthesis of unsaturated fatty acids GLS / GLS1 Glutaminase Major enzyme yielding glutamate from glutamine Nucleotide synthesis PPAT Phosphoribosyl pyrophosphate amidotransferase Aminoacid synthesis BCAT1 Branched chain aminoacid transaminase 1, cytosolic Eicosanoid synthesis ALOX5 / 5- LOX Alcool metabolism ALDH3A2 / FALDH / ALDH10 ALDH1B1 / ALDH5 Arachidonate 5- lipoxygenase Aldehyde dehydrogenase 3 family, member A2 Aldehyde dehydrogenase 1 family, member B1 Regulation of the intracellular redox environment. Catalyzes the first step of de novo purine nucleotide biosythetic pathway / Provides purines for FAD(H 2 ), NAD(H), NADP(H), coenzyme A, DNA and RNA biosynthesis Transamination of branchedchain alpha-keto acids to branched-chain L-amino acids / Essential for cell growth Synthesis of leukotrienes, 5- HETE and 12-HETE from arachidonic acid Detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation Upregulated in tumors GSS / GSHS Glutathione synthetase Conversion of gamma-lglutamyl-l-cysteine to glutathione TXNRD1 TXNRD2 Metabolism regulation IGF1R Thioredoxin reductase 1 Thioredoxin reductase 2 Insulin-like growth factor 1 receptor Reduction of the active site disulfide of thioredoxin / Regulation of the intracellular redox environment Same as TXRND1 Tyrosine kinase playing a critical role in AKT / PKB activation and transformation Decreased glutamine levels in patients with aggressive CLL to provide metabolic molecules from glutamate and reductive power for fatty acid biosynthesis by NADPH production by malate dehydrogenase Increased levels of both 5 -AMP and 5 - GMP for DNA synthesis Decreased levels of 12-HETE, possibly due to decreased synthesis or increased secretion of eicosanoids

IGFBP3 PIK3IP1 PDPK1 AKT2 / PKBB PPARα / NR1C1 TP53 TPR3INP1 IGF1 Binding protein- 3 Phosphoinositide-3- kinase interacting protein 1 3-phosphoinositide dependent protein kinase-1 v-akt murine thymoma viral oncogene homolog 2 Peroxisome proliferator-activated receptor α Tumor Suppressor protein 53 tumor protein p53 inducible nuclear protein 1 events / Works upstream of PI3 kinase / Responsible for IGF1 anabolic effects Increases IGF1 half-life by allowing it to evade renal clearance Negative regulator of PIK3 Phosphorylation of AKT/PKB kinases Glucose and lipid metabolism Nuclear receptor / Activation of genes encoding proteins implicated in cellular fatty acid uptake, fatty acid oxydation, fatty acid transport into the mitochondrium, ketone body formation and cellular carnithine uptake Powerful anti-tumor factor / Opposes pro-tumor metabolism Tumor suppressor Significant lower levels of glucose and glucose-6-phosphate indicative of increased glucose utilisation ( Warburg effect ) / Higher fatty acid levels Higher levels of essential, mediumand long-chain fatty acids compatible with enhanced fatty acid biosynthesis

Figure S1. MiR-125b expression significantly decreases, while that of mir-155 significantly increases in CLL patients compare to purified B cells from healthy donors. (A) - (C). The relative levels of mir-125b (A), mir-155 (B) and mir-125a (C) in CLL patients were determined by qrt-pcr. P values (Student t test) are given for Indolent [n = 6 for (A) and (B), n = 9 for (C)] and Aggressive [n = 6 for (A) and (B), n = 9 for (C)] versus Healthy [n = 6 for (A), (B) and (C)]. Boxes include values from the first to the third quartiles; o, extreme data points; +, median; x, mean ± standard deviation.

Figure S2. 17p deletions in IND or AGG CLL has no measurable effects on mir-125b and mir-155 expression. (A), (B). The relative levels of mir-125b (A) and mir-155 (B) in each of the 15 HD as well as in a panel of patients with IND [n=35, of whom 9 with del(17p)] or AGG [n=38, of whom 9 with del(17p)] form of CLL, as indicated, were measured by qrt-pcr. The same data were used for panels A and B of Fig. 1.

Figure S3. Transfecting DAUDI cells with 125b-I increases slightly but significantly the expression of luciferase constructs containing PCTP, LIPA or GSS 3 -UTRs. Luciferase assays showing the effects of an antisense mir-125b inhibitory RNA (125b-I) on the expression of luciferase constructs containing the indicated 3 -UTRs in DAUDI cells. Values represent the mean ± standard deviation (n = 4). P values (Student t test) are given for 125b-I versus control. Figure S4. MiR-125b targets transcripts encoding transcription factors of the IKAROS family. Luciferase assays were done in MeG01 cells as previously described 24 using luciferase constructs containing IKZF2, IKZF3 or IKZF4 3 -UTR. Luciferase assays were performed 48 hours following cell transfection. Values represent the mean ± standard deviation (n = 4). P values (student t test) are given for mir-125b versus control.