Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
ADDITIONAL FILE 2: TABLE S1 List of metabolite integrals and assignments obtained from NMR urine spectra Metabolite ID 1 2 3 4 5 6 7 8 9 10 11 Pregnanolone-3G Pregnanediol-3G UA 0.75(d) Estrogen metabolite UA 0.93(s) Leucine Isoleucine Valine 3-hydroxyisobutyrate 4-deoxyerythronic acid UA 1.15 (d) [3.45, 3.54] 12 3-hydroxybutyrate/3aminoisobutyrate 13 4-deoxythreonic acid 14 UA 1.25 15 3-hydroxyisovalerate 16 UA 1.29(s) 17 Lactate 18 2-hydroxyisobutyrate 19 Alanine 20 UA 1.67(s) 21 Lysine Abbreviation Chemical shift Integral range 1 (ppm) Integral range 2 (ppm) Assignment Metabolic class Pn3-G P3-G Leu Iso Val 3-HB 4-DEA - 0.58 (s) 0.63 (s) 0.75 (d) 0.78 (s) 0.93 (s) 0.96 (t) 1.01 (d) 1.05 (d) 1.08 (d) 1.11 (d) 1.15 (d) 0.55 0.6176 0.741 0.7774 0.9311 0.9503 1.005 1.034 1.063 1.097 1.132 0.57 0.64 0.76 0.79 0.94 0.97 1.03 1.06 1.09 1.12 1.16 Steroid and steroid derivates Steroid and steroid derivates Steroid and steroid derivates Steroid and steroid derivates Unknown BCAAs catabolism BCAAs catabolism BCAAs catabolism BCAAs catabolism Glucose metabolism Glucose metabolism 3-HB/3-AB 1.20 (ov.) 1.17 1.21 Fraction, spike-in* Fraction, spike-in, LC-MS/MS Fraction, Spike-in 2D NMR 2D NMR 2D NMR 2D NMR, fractions, spike-in 2D NMR 2D NMR (organic acid with similar structure to 3-hydroxyisobutyrate) 2D NMR 4-DTA 3-HV Lac 2-HB Ala Lys 1.24 (d) 1.25 (d) 1.27 (s) 1.222 1.244 1.264 1.282 1.32 1.355 1.472 1.655 1.701 1.24 1.26 1.28 1.29 1.35 1.37 1.51 1.68 1.76 2D NMR 2D NMR 2D NMR 2D NMR, spike-in 2D NMR 2D NMR, Chenomx Glucose metabolism Unknown Glucose metabolism Unknown Glucose metabolism BCAAs catabolism Glucose metabolism Unknown Glucose metabolism 1.33 (d) 1.36 (s) 1.48 (d) 1.67 (s) 1.73 (m) 1 Glucose metabolism 22 Acetate 23 UA 1.99(t) 24 N-acetyl glycoprotein fragments NAG 1.92 (s) 1.99(t) 2.04 (s) 1.914 1.97 2.022 1.93 2.00 2.05 Literature Literature 25 N-acetyl neuraminic acid NAC 2.06 (s) 2.054 2.09 Literature 26 27 28 29 PCS 5-OP - 2.24 (s) 2.35 (s) 2.40 (m) 2.41 (s) 2.229 2.339 2.387 2.4 2.25 2.355 2.40 2.42 Literature 2D NMR 2D NMR, fractions, spike-in Literature Glu - 2.45 (m) 2.55 (d) 2.43 2.5 2.47 2.58 2D NMR 2D NMR 2.587 2.716 2.774 2.818 2.861 2.9 2.923 3.027 2.64 2.74 2.79 2.85 2.88 2.91 2.94 3.07 2D NMR Literature Literature 2D NMR, spike-in Spike-in Literature 3.201 3.223 3.261 3.297 3.362 3.21 3.24 3.29 3.31 3.37 Literature Literature Literature Literature Literature 3.561 3.58 Literature Acetone P-cresol sulfate Pyroglutamate (5-oxoproline) Succinate 30 Glutamine 31 Citrate 32 33 34 35 36 37 38 39 3-aminoisobutyrate Dimethylamine UA 2.78(s) UA 2.83(s) Trimethylamine UA 2.9 (N-acetyl peak) Dimethylglycine Creatinine+creatine 3-AB DMA TMA DMG Creat2 40 41 42 43 44 Choline Carnitine Trimethylamine oxide Proline betaine Scyllo-inositol TMAO PB SIN 2.62 (m) 2.72 (s) 2.78 (s) 2.83 (s) 2.87 (s) 2.90 2.93 (s) 3.05 (s) ov. 3.20 (s) 3.23 (s) 3.27 (s) 3.30 (s) 3.36 (s) Gly 3.57 (s) 45 Glycine 2 TCA cycle Unknown Amino sugar and nucleotide sugar metabolism Amino sugar and nucleotide sugar metabolism Oxidative stress Bacterial origin Oxidative stress TCA cycle and mitochondrial oxidative stress Glucose metabolism TCA cycle and mitochondrial oxidative stress BCAAs catabolism Alkylamines Unknown Unknown Alkylamines/bacterial origin Oxidative stress Unknown Amino Acids and Derivatives Gluconeogenesis Oxidative stress Alkylamines/bacterial origin Pyrrolidines Nicotinate and nicotinamide metabolism Gluconeogenesis 46 47 48 49 50 51 52 UA 3.8(s) UA 3.93(s) UA 3.95(s) UA 6.48(d) Fumarate UA 6.59(s) Furoylglycine FG 3.8(s) 3.93(s) 3.95(s) 6.48(d) 6.52 (s) 6.59 (s) 6.64 (dd) 3.792 3.927 3.946 6.477 6.521 6.585 6.636 3.81 3.94 3.96 6.49 6.53 6.61 6.66 Literature 2D NMR, fractions 2PY 6.66 (s) 6.657 6.67 2D NMR HPA Tyr PAG 3-IS - 6.87 (d) 6.90 (d) 7.32 7.37 (t) 7.51 (d) 7.55 (t) 7.68(s) 8.46 (s) 8.79(d) 6.851 6.89 7.306 7.343 7.494 7.527 7.672 8.453 8.772 6.88 6.92 7.34 7.38 7.52 7.58 7.69 8.47 8.81 2D NMR, STORM**, spike-in 2D NMR 2D NMR 2D NMR, spike-in 2D NMR Literature - 63 N-Methylnicotinic acid NMNA 9.13 (s) 9.113 9.14 2D NMR, spike-in 64 N¹-Methyl-nicotinamide NMN 9.28 (s) 9.269 9.30 2D NMR, spike-in 53 N-methyl-2-pyridone-5carboxamide 54 p-hydroxyphenylacetate 55 Tyrosine 56 UA 7.32 57 Phenylacetylglutamine 58 3-Indoxylsulfate 59 Hippurate 60 UA 7.68(s) 61 Formate 62 UA 8.79(d) unknown Unknown Unknown Unknown Oxidative stress Unknown Nicotinate and nicotinamide metabolism Nicotinate and nicotinamide metabolism Bacterial origin Amino Acids and Derivatives Unknown Bacterial origin Bacterial origin Bacterial origin Unknown Organic acids Nicotinate and nicotinamide metabolism Nicotinate and nicotinamide metabolism Nicotinate and nicotinamide metabolism Abbreviations: UA, unassigned * The method of multiple spike-in of authentic standards in the original sample allowed to validate the identity of NMR signals. The identity of P3G was confirmed by chromatographic isolation of the target feature (SI Methods) and comparison of MS/MS spectra to an authentic reference compound in accordance with reported guidelines for metabolite identification (14). 3 **Citation for STORM: Subset Optimization by Reference Matching (STORM): An Optimized Statistical Approach for Recovery of Metabolic Biomarker Structural Information from 1H NMR Spectra of Biofluids. Joram M. Posma, Isabel Garcia-Perez, Maria De Iorio, John C. Lindon, Paul Elliott, Elaine Holmes, Timothy M. D. Ebbels, and Jeremy K. Nicholson. Analytical Chemistry 2012 84 (24), 10694-10701 DOI: 10.1021/ac302360v 4