#METABOLOMICS WORKBENCH BPnorman_20220928_081002 DATATRACK_ID:3478 STUDY_ID:ST002297 ANALYSIS_ID:AN003753 PROJECT_ID:PR001471 VERSION 1 CREATED_ON September 30, 2022, 8:19 am #PROJECT PR:PROJECT_TITLE Metabolomic analysis in SONIA 2, a phase 3 international randomised-controlled PR:PROJECT_TITLE trial of nitisinone in alkaptonuria (AKU) PR:PROJECT_SUMMARY Abstract from main SONIA 2 publication: Background Alkaptonuria is a rare, PR:PROJECT_SUMMARY genetic, multisystem disease characterised by the accumulation of homogentisic PR:PROJECT_SUMMARY acid (HGA). No HGA-lowering therapy has been approved to date. The aim of SONIA PR:PROJECT_SUMMARY 2 was to investigate the efficacy and safety of once-daily nitisinone for PR:PROJECT_SUMMARY reducing HGA excretion in patients with alkaptonuria and to evaluate whether PR:PROJECT_SUMMARY nitisinone has a clinical benefit. Methods SONIA 2 was a 4-year, open-label, PR:PROJECT_SUMMARY evaluator-blind, randomised, no treatment controlled, parallel-group study done PR:PROJECT_SUMMARY at three sites in the UK, France, and Slovakia. Patients aged 25 years or older PR:PROJECT_SUMMARY with confirmed alkaptonuria and any clinical disease manifestations were PR:PROJECT_SUMMARY randomly assigned (1:1) to receive either oral nitisinone 10 mg daily or no PR:PROJECT_SUMMARY treatment. Patients could not be masked to treatment due to colour changes in PR:PROJECT_SUMMARY the urine, but the study was evaluator-blinded as far as possible. The primary PR:PROJECT_SUMMARY endpoint was daily urinary HGA excretion (u-HGA24) after 12 months. Clinical PR:PROJECT_SUMMARY evaluation Alkaptonuria Severity Score Index (cAKUSSI) score was assessed at 12, PR:PROJECT_SUMMARY 24, 36, and 48 months. Efficacy variables were analysed in all randomly assigned PR:PROJECT_SUMMARY patients with a valid u-HGA24 measurement at baseline. Safety variables were PR:PROJECT_SUMMARY analysed in all randomly assigned patients. The study was registered at PR:PROJECT_SUMMARY ClinicalTrials.gov (NCT01916382). Findings Between May 7, 2014, and Feb 16, PR:PROJECT_SUMMARY 2015, 139 patients were screened, of whom 138 were included in the study, with PR:PROJECT_SUMMARY 69 patients randomly assigned to each group. 55 patients in the nitisinone group PR:PROJECT_SUMMARY and 53 in the control group completed the study. u-HGA24 at 12 months was PR:PROJECT_SUMMARY significantly decreased by 99·7% in the nitisinone group compared with the PR:PROJECT_SUMMARY control group (adjusted geometric mean ratio of nitisinone/control 0·003 [95% PR:PROJECT_SUMMARY CI 0·003 to 0·004], p<0·0001). At 48 months, the increase in cAKUSSI score PR:PROJECT_SUMMARY from baseline was significantly lower in the nitisinone group compared with the PR:PROJECT_SUMMARY control group (adjusted mean difference –8·6 points [–16·0 to –1·2], PR:PROJECT_SUMMARY p=0·023). 400 adverse events occurred in 59 (86%) patients in the nitisinone PR:PROJECT_SUMMARY group and 284 events occurred in 57 (83%) patients in the control group. No PR:PROJECT_SUMMARY treatment-related deaths occurred. Interpretation Nitisinone 10 mg daily was PR:PROJECT_SUMMARY well tolerated and effective in reducing urinary excretion of HGA. Nitisinone PR:PROJECT_SUMMARY decreased ochronosis and improved clinical signs, indicating a slower disease PR:PROJECT_SUMMARY progression. PR:INSTITUTE University of Liverpool Institute of Life Course & Medical Sciences PR:DEPARTMENT Department of Musculoskeletal & Ageing Science PR:LAST_NAME Brendan PR:FIRST_NAME Norman PR:ADDRESS William Henry Duncan Building, 6 West Derby Street, Liverpool, UK. L7 8TX PR:EMAIL bnorman@liverpool.ac.uk PR:PHONE +447809606497 PR:FUNDING_SOURCE European Commission for the Framework 7 grant award (DevelopAKUre, project PR:FUNDING_SOURCE number: 304985), Alkaptonuria Society (BPN is funded by the Alkaptonuria Society PR:FUNDING_SOURCE through a Sireau Fellowship Award). #STUDY ST:STUDY_TITLE Comprehensive biotransformation analysis of phenylalanine-tyrosine metabolism ST:STUDY_TITLE reveals alternative routes of metabolite clearance in nitisinone-treated ST:STUDY_TITLE alkaptonuria (Urine metabolomic analysis) ST:STUDY_SUMMARY Background: Metabolomic analyses in alkaptonuria (AKU) have recently revealed ST:STUDY_SUMMARY alternative pathways in phenylalanine-tyrosine (phe-tyr) metabolism from ST:STUDY_SUMMARY biotransformation of homo-gentisic acid (HGA), the active molecule in this ST:STUDY_SUMMARY disease. The aim of this research was to study the phe-tyr metabolic pathway and ST:STUDY_SUMMARY whether the metabolites upstream of HGA, increased in nitisinone-treated ST:STUDY_SUMMARY patients, also undergo phase 1 and 2 biotransformation reactions. Methods: ST:STUDY_SUMMARY Metabolomic analyses were performed on serum and urine from patients partaking ST:STUDY_SUMMARY in the SONIA 2 phase 3 international randomised-controlled trial of nitisinone ST:STUDY_SUMMARY in AKU (EudraCT no. 2013-001633-41). Serum and urine samples were taken from the ST:STUDY_SUMMARY same patients at baseline (pre-nitisinone) then at 24 and 48 months on ST:STUDY_SUMMARY nitisinone treatment (patients N = 47 serum; 53 urine) or no treatment (patients ST:STUDY_SUMMARY N = 45 serum; 50 urine). Targeted feature extraction was per-formed to ST:STUDY_SUMMARY specifically mine data for the entire complement of theoretically predicted ST:STUDY_SUMMARY phase 1 and 2 biotransformation products derived from phenylalanine, tyrosine, ST:STUDY_SUMMARY 4-hydroxyphenylpyruvic acid and 4-hydroxyphenyllactic acid, in addition to ST:STUDY_SUMMARY phenylalanine-derived metabolites with known increases in phenylketonuria. ST:STUDY_SUMMARY Results: In total, we ob-served 13 phase 1 and 2 biotransformation products from ST:STUDY_SUMMARY phenylalanine through to HGA. Each of these products were observed in urine and ST:STUDY_SUMMARY two were detected in serum. The derivatives of the metabolites upstream of HGA ST:STUDY_SUMMARY were markedly increased in urine of nitisinone-treated patients (fold change ST:STUDY_SUMMARY 1.2-16.2) and increases in 12 of these compounds were directly proportional to ST:STUDY_SUMMARY the degree of nitisinone-induced hypertyrosinaemia (correlation coefficient with ST:STUDY_SUMMARY serum tyrosine = 0.2-0.7). Increases in the urinary phenylalanine metabolites ST:STUDY_SUMMARY were also observed across consecutive visits in the treated group. Conclusions: ST:STUDY_SUMMARY Nitisinone treatment results in marked increases in a wider network of phe-tyr ST:STUDY_SUMMARY metabolites than shown before. This network comprises alternative ST:STUDY_SUMMARY biotransformation products from the major metabolites of this pathway, produced ST:STUDY_SUMMARY by reactions including hydration (phase 1) and bioconjugation (phase 2) of ST:STUDY_SUMMARY acetyl, methyl, acetylcysteine, glucuronide, glycine and sulfate groups. We ST:STUDY_SUMMARY propose that these alternative routes of phe-tyr metabolism, predominantly in ST:STUDY_SUMMARY urine, minimise tyrosinaemia as well as phenylalanaemia. ST:INSTITUTE University of Liverpool Institute of Life Course & Medical Sciences ST:DEPARTMENT Department of Musculoskeletal & Ageing Science ST:LAST_NAME Brendan ST:FIRST_NAME Norman ST:ADDRESS William Henry Duncan Building, 6 West Derby Street, Liverpool, UK. L7 8TX ST:EMAIL bnorman@liverpool.ac.uk ST:NUM_GROUPS 2 ST:TOTAL_SUBJECTS 103 ST:NUM_MALES 65 ST:NUM_FEMALES 38 ST:STUDY_TYPE Urine metabolomic analysis (study 2 of 2) ST:PHONE +447809606497 #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS F01 F01_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=7.1; sTyr groups=1) <701; RAW_FILE_NAME=F01_V1 SUBJECT_SAMPLE_FACTORS F01 F01_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=6.3; sTyr groups=3) 901-1100; RAW_FILE_NAME=F01_V4 SUBJECT_SAMPLE_FACTORS F01 F01_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=2.5; sTyr groups=3) 901-1100; RAW_FILE_NAME=F01_V6 SUBJECT_SAMPLE_FACTORS F02 F02_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=11.9; sTyr groups=None; RAW_FILE_NAME=F02_V1 SUBJECT_SAMPLE_FACTORS F02 F02_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=12.2; sTyr groups=None; RAW_FILE_NAME=F02_V4 SUBJECT_SAMPLE_FACTORS F02 F02_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=7.5; sTyr groups=None; RAW_FILE_NAME=F2_V6 SUBJECT_SAMPLE_FACTORS F03 F03_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=15; sTyr groups=None; RAW_FILE_NAME=F03_V1 SUBJECT_SAMPLE_FACTORS F03 F03_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=13.8; sTyr groups=None; RAW_FILE_NAME=F03_V4 SUBJECT_SAMPLE_FACTORS F03 F03_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=11; sTyr groups=None; RAW_FILE_NAME=F03_V6 SUBJECT_SAMPLE_FACTORS F04 F04_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=9.5; sTyr groups=1) <701; RAW_FILE_NAME=F04_V1 SUBJECT_SAMPLE_FACTORS F04 F04_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=13.3; sTyr groups=2) 701-900; RAW_FILE_NAME=F04_V4 SUBJECT_SAMPLE_FACTORS F04 F04_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=11.4; 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24h Creatinine=8.9; sTyr groups=None; RAW_FILE_NAME=L03_V1 SUBJECT_SAMPLE_FACTORS L03 L03_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=10.7; sTyr groups=None; RAW_FILE_NAME=L3_V4 SUBJECT_SAMPLE_FACTORS L03 L03_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=5.6; sTyr groups=None; RAW_FILE_NAME=L03_V6 SUBJECT_SAMPLE_FACTORS L06 L06_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=6.9; sTyr groups=1) <701; RAW_FILE_NAME=L06_V1 SUBJECT_SAMPLE_FACTORS L06 L06_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=7.3; sTyr groups=1) <701; RAW_FILE_NAME=L06_V4 SUBJECT_SAMPLE_FACTORS L06 L06_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=3.4; sTyr groups=4) >1100; RAW_FILE_NAME=L06_V6 SUBJECT_SAMPLE_FACTORS L07 L07_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=8.8; sTyr groups=1) <701; RAW_FILE_NAME=L07_V1 SUBJECT_SAMPLE_FACTORS L07 L07_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=6.5; sTyr groups=3) 901-1100; RAW_FILE_NAME=L07_V4 SUBJECT_SAMPLE_FACTORS L07 L07_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=7.7; sTyr groups=3) 901-1100; RAW_FILE_NAME=L07_V6 SUBJECT_SAMPLE_FACTORS L08 L08_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=12.8; sTyr groups=1) <701; RAW_FILE_NAME=L08_V1 SUBJECT_SAMPLE_FACTORS L08 L08_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=11.4; sTyr groups=1) <701; RAW_FILE_NAME=L08_V4 SUBJECT_SAMPLE_FACTORS L08 L08_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=11.3; sTyr groups=1) <701; RAW_FILE_NAME=L08_V6 SUBJECT_SAMPLE_FACTORS L09 L09_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=4.5; sTyr groups=None; RAW_FILE_NAME=L09_V1 SUBJECT_SAMPLE_FACTORS L09 L09_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=6; sTyr groups=None; RAW_FILE_NAME=L09_V4 SUBJECT_SAMPLE_FACTORS L09 L09_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=5.5; sTyr groups=None; RAW_FILE_NAME=L09_V6 SUBJECT_SAMPLE_FACTORS L10 L10_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=6.2; sTyr groups=1) <701; RAW_FILE_NAME=L10_V1 SUBJECT_SAMPLE_FACTORS L10 L10_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=6.6; sTyr groups=2) 701-900; RAW_FILE_NAME=L10_V4 SUBJECT_SAMPLE_FACTORS L10 L10_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=7.4; sTyr groups=3) 901-1100; RAW_FILE_NAME=L10_V6 SUBJECT_SAMPLE_FACTORS L11 L11_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=9.1; sTyr groups=None; RAW_FILE_NAME=L11_V1 SUBJECT_SAMPLE_FACTORS L11 L11_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=6.6; sTyr groups=None; RAW_FILE_NAME=L11_V4 SUBJECT_SAMPLE_FACTORS L11 L11_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=4.7; sTyr groups=None; RAW_FILE_NAME=L11_V6 SUBJECT_SAMPLE_FACTORS L12 L12_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=8.4; sTyr groups=1) <701; RAW_FILE_NAME=L12_V1 SUBJECT_SAMPLE_FACTORS L12 L12_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=11.2; sTyr groups=2) 701-900; RAW_FILE_NAME=L12_V4 SUBJECT_SAMPLE_FACTORS L12 L12_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=8.6; sTyr groups=3) 901-1100; RAW_FILE_NAME=L12_V6 SUBJECT_SAMPLE_FACTORS L13 L13_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=10.2; sTyr groups=None; RAW_FILE_NAME=L13_V1 SUBJECT_SAMPLE_FACTORS L13 L13_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=6.4; sTyr groups=None; RAW_FILE_NAME=L13_V4 SUBJECT_SAMPLE_FACTORS L13 L13_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=7; sTyr groups=None; RAW_FILE_NAME=L13_V6 SUBJECT_SAMPLE_FACTORS L14 L14_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=10.2; sTyr groups=1) <701; RAW_FILE_NAME=L14_V1 SUBJECT_SAMPLE_FACTORS L14 L14_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=13.5; sTyr groups=2) 701-900; RAW_FILE_NAME=L14_V4 SUBJECT_SAMPLE_FACTORS L14 L14_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=7.9; sTyr groups=2) 701-900; RAW_FILE_NAME=L14_V6 SUBJECT_SAMPLE_FACTORS L15 L15_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=13.2; sTyr groups=None; RAW_FILE_NAME=L15_V1 SUBJECT_SAMPLE_FACTORS L15 L15_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=11.3; sTyr groups=None; RAW_FILE_NAME=L15_V4 SUBJECT_SAMPLE_FACTORS L15 L15_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=7.6; sTyr groups=None; RAW_FILE_NAME=L15_V6 SUBJECT_SAMPLE_FACTORS L16 L16_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=14.3; sTyr groups=1) <701; RAW_FILE_NAME=L16_V1 SUBJECT_SAMPLE_FACTORS L16 L16_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=11.2; sTyr groups=3) 901-1100; RAW_FILE_NAME=L16_V4 SUBJECT_SAMPLE_FACTORS L16 L16_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=8.7; sTyr groups=3) 901-1100; RAW_FILE_NAME=L16_V6 SUBJECT_SAMPLE_FACTORS L17 L17_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=13.7; sTyr groups=None; RAW_FILE_NAME=L17_V1 SUBJECT_SAMPLE_FACTORS L17 L17_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=13.5; sTyr groups=None; RAW_FILE_NAME=L17_V4 SUBJECT_SAMPLE_FACTORS L17 L17_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=7.2; sTyr groups=None; RAW_FILE_NAME=L17_V6 SUBJECT_SAMPLE_FACTORS L18 L18_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=12.5; sTyr groups=1) <701; RAW_FILE_NAME=L18_V1 SUBJECT_SAMPLE_FACTORS L18 L18_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=10.5; sTyr groups=3) 901-1100; RAW_FILE_NAME=L18_V4 SUBJECT_SAMPLE_FACTORS L18 L18_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=10.6; sTyr groups=3) 901-1100; RAW_FILE_NAME=L18_V6 SUBJECT_SAMPLE_FACTORS L21 L21_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=8.6; sTyr groups=None; RAW_FILE_NAME=L21_V1 SUBJECT_SAMPLE_FACTORS L21 L21_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=9.9; sTyr groups=None; RAW_FILE_NAME=L21_V4 SUBJECT_SAMPLE_FACTORS L21 L21_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=6.8; sTyr groups=None; RAW_FILE_NAME=L21_V6 SUBJECT_SAMPLE_FACTORS L22 L22_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=9.4; sTyr groups=1) <701; RAW_FILE_NAME=L22_V1 SUBJECT_SAMPLE_FACTORS L22 L22_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=10.5; sTyr groups=1) <701; RAW_FILE_NAME=L22_V4 SUBJECT_SAMPLE_FACTORS L22 L22_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=4.3; sTyr groups=1) <701; RAW_FILE_NAME=L22_V6 SUBJECT_SAMPLE_FACTORS L23 L23_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=8.2; sTyr groups=None; RAW_FILE_NAME=L23_V1 SUBJECT_SAMPLE_FACTORS L23 L23_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=8.3; sTyr groups=None; RAW_FILE_NAME=L23_V4 SUBJECT_SAMPLE_FACTORS L23 L23_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=3.4; sTyr groups=None; RAW_FILE_NAME=L23_V6 SUBJECT_SAMPLE_FACTORS L24 L24_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=12.1; sTyr groups=None; RAW_FILE_NAME=L24_V1 SUBJECT_SAMPLE_FACTORS L24 L24_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=13.4; sTyr groups=None; RAW_FILE_NAME=L24_V4 SUBJECT_SAMPLE_FACTORS L24 L24_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=7.7; sTyr groups=None; RAW_FILE_NAME=L24_V6 SUBJECT_SAMPLE_FACTORS L28 L28_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=12.9; sTyr groups=1) <701; RAW_FILE_NAME=L28_V1 SUBJECT_SAMPLE_FACTORS L28 L28_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=13.3; sTyr groups=4) >1100; RAW_FILE_NAME=L28_V4 SUBJECT_SAMPLE_FACTORS L28 L28_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=11.9; sTyr groups=4) >1100; RAW_FILE_NAME=L28_V6 SUBJECT_SAMPLE_FACTORS L29 L29_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=7.7; sTyr groups=None; RAW_FILE_NAME=L29_V1 SUBJECT_SAMPLE_FACTORS L29 L29_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=9; sTyr groups=None; RAW_FILE_NAME=L29_V4 SUBJECT_SAMPLE_FACTORS L29 L29_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=5.5; sTyr groups=None; RAW_FILE_NAME=L29_V6 SUBJECT_SAMPLE_FACTORS L30 L30_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=11.6; sTyr groups=1) <701; RAW_FILE_NAME=L30_V1 SUBJECT_SAMPLE_FACTORS L30 L30_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=12.7; sTyr groups=3) 901-1100; RAW_FILE_NAME=L30_V4 SUBJECT_SAMPLE_FACTORS L30 L30_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=7; sTyr groups=4) >1100; RAW_FILE_NAME=L30_V6 SUBJECT_SAMPLE_FACTORS L31 L31_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=6.9; sTyr groups=None; RAW_FILE_NAME=L31_V1 SUBJECT_SAMPLE_FACTORS L31 L31_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=5.6; sTyr groups=None; RAW_FILE_NAME=L31_V4 SUBJECT_SAMPLE_FACTORS L31 L31_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=3.4; sTyr groups=None; RAW_FILE_NAME=L31_V6 SUBJECT_SAMPLE_FACTORS L33 L33_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=8.7; sTyr groups=1) <701; RAW_FILE_NAME=L33_V1 SUBJECT_SAMPLE_FACTORS L33 L33_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=8.3; sTyr groups=2) 701-900; RAW_FILE_NAME=L33_V4 SUBJECT_SAMPLE_FACTORS L33 L33_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=5.2; sTyr groups=2) 701-900; RAW_FILE_NAME=L33_V6 SUBJECT_SAMPLE_FACTORS L35 L35_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=13.9; sTyr groups=1) <701; RAW_FILE_NAME=L35_V1 SUBJECT_SAMPLE_FACTORS L35 L35_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=9.8; sTyr groups=1) <701; RAW_FILE_NAME=L35_V4 SUBJECT_SAMPLE_FACTORS L35 L35_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=7.4; sTyr groups=1) <701; RAW_FILE_NAME=L35_V6 SUBJECT_SAMPLE_FACTORS L37 L37_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=11.7; sTyr groups=None; RAW_FILE_NAME=L37_V1 SUBJECT_SAMPLE_FACTORS L37 L37_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=14.6; sTyr groups=None; RAW_FILE_NAME=L37_V4 SUBJECT_SAMPLE_FACTORS L37 L37_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=11.7; sTyr groups=None; RAW_FILE_NAME=L37_V6 SUBJECT_SAMPLE_FACTORS L38 L38_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=7.5; sTyr groups=None; RAW_FILE_NAME=L38_V1 SUBJECT_SAMPLE_FACTORS L38 L38_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=9.5; sTyr groups=None; RAW_FILE_NAME=L38_V4 SUBJECT_SAMPLE_FACTORS L38 L38_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=4.7; sTyr groups=None; RAW_FILE_NAME=L38_V6 SUBJECT_SAMPLE_FACTORS L40 L40_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=10.5; sTyr groups=1) <701; RAW_FILE_NAME=L40_V1 SUBJECT_SAMPLE_FACTORS L40 L40_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=14.3; sTyr groups=1) <701; RAW_FILE_NAME=L40_V4 SUBJECT_SAMPLE_FACTORS L40 L40_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=11; sTyr groups=2) 701-900; RAW_FILE_NAME=L40_V6 SUBJECT_SAMPLE_FACTORS P01 P01_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=9.4; sTyr groups=None; RAW_FILE_NAME=P01_V1 SUBJECT_SAMPLE_FACTORS P01 P01_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=9.5; sTyr groups=None; RAW_FILE_NAME=P01_V4 SUBJECT_SAMPLE_FACTORS P01 P01_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=10.9; sTyr groups=None; RAW_FILE_NAME=P01_V6 SUBJECT_SAMPLE_FACTORS P02 P02_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=9.3; sTyr groups=1) <701; RAW_FILE_NAME=P02_V1 SUBJECT_SAMPLE_FACTORS P02 P02_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=10.1; sTyr groups=3) 901-1100; RAW_FILE_NAME=P02_V4 SUBJECT_SAMPLE_FACTORS P02 P02_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=5; sTyr groups=2) 701-900; RAW_FILE_NAME=P02_V6 SUBJECT_SAMPLE_FACTORS P03 P03_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=14.6; sTyr groups=1) <701; RAW_FILE_NAME=P03_V1 SUBJECT_SAMPLE_FACTORS P03 P03_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=17.6; sTyr groups=2) 701-900; RAW_FILE_NAME=P03_V4 SUBJECT_SAMPLE_FACTORS P03 P03_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=14.3; sTyr groups=2) 701-900; RAW_FILE_NAME=P03_V6 SUBJECT_SAMPLE_FACTORS P05 P05_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=10.1; sTyr groups=None; RAW_FILE_NAME=P05_V1 SUBJECT_SAMPLE_FACTORS P05 P05_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=14.6; sTyr groups=None; RAW_FILE_NAME=P05_V4 SUBJECT_SAMPLE_FACTORS P05 P05_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=5.6; sTyr groups=None; RAW_FILE_NAME=P05_V6 SUBJECT_SAMPLE_FACTORS P06 P06_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=12.5; sTyr groups=None; RAW_FILE_NAME=P06_V1 SUBJECT_SAMPLE_FACTORS P06 P06_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=12.7; sTyr groups=None; RAW_FILE_NAME=P06_V4 SUBJECT_SAMPLE_FACTORS P06 P06_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=11.1; sTyr groups=None; RAW_FILE_NAME=P06_V6 SUBJECT_SAMPLE_FACTORS P07 P07_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=10.4; sTyr groups=1) <701; RAW_FILE_NAME=P07_V1 SUBJECT_SAMPLE_FACTORS P07 P07_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=10.7; sTyr groups=3) 901-1100; RAW_FILE_NAME=P07_V4 SUBJECT_SAMPLE_FACTORS P07 P07_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=7; sTyr groups=2) 701-900; RAW_FILE_NAME=P07_V6 SUBJECT_SAMPLE_FACTORS P09 P09_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=12.6; sTyr groups=None; RAW_FILE_NAME=P09_V1 SUBJECT_SAMPLE_FACTORS P09 P09_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=14.3; sTyr groups=None; RAW_FILE_NAME=P09_V4 SUBJECT_SAMPLE_FACTORS P09 P09_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=12; sTyr groups=None; RAW_FILE_NAME=P09_V6 SUBJECT_SAMPLE_FACTORS P11 P11_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=12.2; sTyr groups=1) <701; RAW_FILE_NAME=P11_V1 SUBJECT_SAMPLE_FACTORS P11 P11_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=12.6; sTyr groups=3) 901-1100; RAW_FILE_NAME=P11_V4 SUBJECT_SAMPLE_FACTORS P11 P11_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=12.2; sTyr groups=3) 901-1100; RAW_FILE_NAME=P11_V6 SUBJECT_SAMPLE_FACTORS P12 P12_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=14.1; sTyr groups=None; RAW_FILE_NAME=P12_V1 SUBJECT_SAMPLE_FACTORS P12 P12_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=11.4; sTyr groups=None; RAW_FILE_NAME=P12_V4 SUBJECT_SAMPLE_FACTORS P12 P12_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=15.8; sTyr groups=None; RAW_FILE_NAME=P12_V6 SUBJECT_SAMPLE_FACTORS P13 P13_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=9.3; sTyr groups=None; RAW_FILE_NAME=P13_V1 SUBJECT_SAMPLE_FACTORS P13 P13_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=9.7; sTyr groups=None; RAW_FILE_NAME=P13_V4 SUBJECT_SAMPLE_FACTORS P13 P13_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=7.4; sTyr groups=None; RAW_FILE_NAME=P13_V6 SUBJECT_SAMPLE_FACTORS P15 P15_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=15.1; sTyr groups=1) <701; RAW_FILE_NAME=P15_V1 SUBJECT_SAMPLE_FACTORS P15 P15_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=12.3; sTyr groups=1) <701; RAW_FILE_NAME=P15_V4 SUBJECT_SAMPLE_FACTORS P15 P15_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=15.7; sTyr groups=1) <701; RAW_FILE_NAME=P15_V6 SUBJECT_SAMPLE_FACTORS P16 P16_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=8.5; sTyr groups=None; RAW_FILE_NAME=P16_V1 SUBJECT_SAMPLE_FACTORS P16 P16_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=10.3; sTyr groups=None; RAW_FILE_NAME=P16_V4 SUBJECT_SAMPLE_FACTORS P16 P16_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=10.1; sTyr groups=None; RAW_FILE_NAME=P16_V6 SUBJECT_SAMPLE_FACTORS P17 P17_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=15.8; sTyr groups=None; RAW_FILE_NAME=P17_V1 SUBJECT_SAMPLE_FACTORS P17 P17_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=13.8; sTyr groups=None; RAW_FILE_NAME=P17_V4 SUBJECT_SAMPLE_FACTORS P17 P17_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=8.3; sTyr groups=None; RAW_FILE_NAME=P17_V6 SUBJECT_SAMPLE_FACTORS P18 P18_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=14.2; sTyr groups=1) <701; RAW_FILE_NAME=P18_V1 SUBJECT_SAMPLE_FACTORS P18 P18_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=14.2; sTyr groups=2) 701-900; RAW_FILE_NAME=P18_V4 SUBJECT_SAMPLE_FACTORS P18 P18_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=11.8; sTyr groups=2) 701-900; RAW_FILE_NAME=P18_V6 SUBJECT_SAMPLE_FACTORS P20 P20_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=12.5; sTyr groups=None; RAW_FILE_NAME=P20_V1 SUBJECT_SAMPLE_FACTORS P20 P20_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=15.1; sTyr groups=None; RAW_FILE_NAME=P20_V4 SUBJECT_SAMPLE_FACTORS P20 P20_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=13.9; sTyr groups=None; RAW_FILE_NAME=P20_V6 SUBJECT_SAMPLE_FACTORS P21 P21_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=18.7; sTyr groups=None; RAW_FILE_NAME=P21_V1 SUBJECT_SAMPLE_FACTORS P21 P21_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=8.7; sTyr groups=None; RAW_FILE_NAME=P21_V4 SUBJECT_SAMPLE_FACTORS P21 P21_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=11.8; sTyr groups=None; RAW_FILE_NAME=P21_V6 SUBJECT_SAMPLE_FACTORS P22 P22_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=9.7; sTyr groups=1) <701; RAW_FILE_NAME=P22_V1 SUBJECT_SAMPLE_FACTORS P22 P22_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=9.6; sTyr groups=2) 701-900; RAW_FILE_NAME=P22_V4 SUBJECT_SAMPLE_FACTORS P22 P22_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=6.7; sTyr groups=4) >1100; RAW_FILE_NAME=P22_V6 SUBJECT_SAMPLE_FACTORS P23 P23_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=16.4; sTyr groups=1) <701; RAW_FILE_NAME=P23_V1 SUBJECT_SAMPLE_FACTORS P23 P23_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=13.9; sTyr groups=4) >1100; RAW_FILE_NAME=P23_V4 SUBJECT_SAMPLE_FACTORS P23 P23_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=11.3; sTyr groups=3) 901-1100; RAW_FILE_NAME=P23_V6 SUBJECT_SAMPLE_FACTORS P24 P24_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=13.1; sTyr groups=None; RAW_FILE_NAME=P24_V1 SUBJECT_SAMPLE_FACTORS P24 P24_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=11.9; sTyr groups=None; RAW_FILE_NAME=P24_V4 SUBJECT_SAMPLE_FACTORS P24 P24_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=8.8; sTyr groups=None; RAW_FILE_NAME=P24_V6 SUBJECT_SAMPLE_FACTORS P26 P26_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=12.6; sTyr groups=1) <701; RAW_FILE_NAME=P26_V1 SUBJECT_SAMPLE_FACTORS P26 P26_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=12; sTyr groups=3) 901-1100; RAW_FILE_NAME=P26_V4 SUBJECT_SAMPLE_FACTORS P26 P26_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=12.5; sTyr groups=4) >1100; RAW_FILE_NAME=P26_V6 SUBJECT_SAMPLE_FACTORS P28 P28_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=18.4; sTyr groups=None; RAW_FILE_NAME=P28_V1 SUBJECT_SAMPLE_FACTORS P28 P28_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=13.9; sTyr groups=None; RAW_FILE_NAME=P28_V4 SUBJECT_SAMPLE_FACTORS P28 P28_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=18.6; sTyr groups=None; RAW_FILE_NAME=P28_V6 SUBJECT_SAMPLE_FACTORS P29 P29_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=9.9; sTyr groups=None; RAW_FILE_NAME=P29_V1 SUBJECT_SAMPLE_FACTORS P29 P29_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=7.6; sTyr groups=None; RAW_FILE_NAME=P29_V4 SUBJECT_SAMPLE_FACTORS P29 P29_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=9.6; sTyr groups=None; RAW_FILE_NAME=P29_V6 SUBJECT_SAMPLE_FACTORS P30 P30_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=13.6; sTyr groups=1) <701; RAW_FILE_NAME=P30_V1 SUBJECT_SAMPLE_FACTORS P30 P30_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=16; sTyr groups=3) 901-1100; RAW_FILE_NAME=P30_V4 SUBJECT_SAMPLE_FACTORS P30 P30_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=16.3; sTyr groups=1) <701; RAW_FILE_NAME=P30_V6 SUBJECT_SAMPLE_FACTORS P31 P31_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=9.7; sTyr groups=1) <701; RAW_FILE_NAME=P31_V1 SUBJECT_SAMPLE_FACTORS P31 P31_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=10.8; sTyr groups=4) >1100; RAW_FILE_NAME=P31_V4 SUBJECT_SAMPLE_FACTORS P31 P31_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=8.4; sTyr groups=3) 901-1100; RAW_FILE_NAME=P31_V6 SUBJECT_SAMPLE_FACTORS P32 P32_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=9.1; sTyr groups=None; RAW_FILE_NAME=P32_V1 SUBJECT_SAMPLE_FACTORS P32 P32_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=11.1; sTyr groups=None; RAW_FILE_NAME=P32_V4 SUBJECT_SAMPLE_FACTORS P32 P32_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=8.5; sTyr groups=None; RAW_FILE_NAME=P32_V6 SUBJECT_SAMPLE_FACTORS P33 P33_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=15.5; sTyr groups=None; RAW_FILE_NAME=P33_V1 SUBJECT_SAMPLE_FACTORS P33 P33_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=14.4; sTyr groups=None; RAW_FILE_NAME=P33_V4 SUBJECT_SAMPLE_FACTORS P33 P33_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=16.9; sTyr groups=None; RAW_FILE_NAME=P33_V6 SUBJECT_SAMPLE_FACTORS P34 P34_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=12.6; sTyr groups=1) <701; RAW_FILE_NAME=P34_V1 SUBJECT_SAMPLE_FACTORS P34 P34_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=15.3; sTyr groups=2) 701-900; RAW_FILE_NAME=P34_V4 SUBJECT_SAMPLE_FACTORS P34 P34_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=25.1; sTyr groups=2) 701-900; RAW_FILE_NAME=P34_V6 SUBJECT_SAMPLE_FACTORS P35 P35_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=6.1; sTyr groups=None; RAW_FILE_NAME=P35_V1 SUBJECT_SAMPLE_FACTORS P35 P35_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=7.3; sTyr groups=None; RAW_FILE_NAME=P35_V4 SUBJECT_SAMPLE_FACTORS P35 P35_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=8.2; sTyr groups=None; RAW_FILE_NAME=P35_V6 SUBJECT_SAMPLE_FACTORS P37 P37_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=15.8; sTyr groups=None; RAW_FILE_NAME=P37_V1 SUBJECT_SAMPLE_FACTORS P37 P37_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=15.7; sTyr groups=None; RAW_FILE_NAME=P37_V4 SUBJECT_SAMPLE_FACTORS P37 P37_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=4; sTyr groups=None; RAW_FILE_NAME=P37_V6 SUBJECT_SAMPLE_FACTORS P39 P39_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=10.5; sTyr groups=1) <701; RAW_FILE_NAME=P39_V1 SUBJECT_SAMPLE_FACTORS P39 P39_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=8.6; sTyr groups=1) <701; RAW_FILE_NAME=P39_V4 SUBJECT_SAMPLE_FACTORS P39 P39_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=3.8; sTyr groups=1) <701; RAW_FILE_NAME=P39_V6 SUBJECT_SAMPLE_FACTORS P40 P40_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=8.4; sTyr groups=1) <701; RAW_FILE_NAME=P40_V1 SUBJECT_SAMPLE_FACTORS P40 P40_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=9.1; sTyr groups=1) <701; RAW_FILE_NAME=P40_V4 SUBJECT_SAMPLE_FACTORS P40 P40_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=9.6; sTyr groups=1) <701; RAW_FILE_NAME=P40_V6 SUBJECT_SAMPLE_FACTORS P41 P41_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=9.2; sTyr groups=None; RAW_FILE_NAME=P41_V1 SUBJECT_SAMPLE_FACTORS P41 P41_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=9.8; sTyr groups=None; RAW_FILE_NAME=P41_V4 SUBJECT_SAMPLE_FACTORS P41 P41_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=9.1; sTyr groups=None; RAW_FILE_NAME=P41_V6 SUBJECT_SAMPLE_FACTORS P42 P42_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=11.3; sTyr groups=None; RAW_FILE_NAME=P42_V1 SUBJECT_SAMPLE_FACTORS P42 P42_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=8.6; sTyr groups=None; RAW_FILE_NAME=P42_V4 SUBJECT_SAMPLE_FACTORS P42 P42_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=2.3; sTyr groups=None; RAW_FILE_NAME=P42_V6 SUBJECT_SAMPLE_FACTORS P43 P43_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=11.3; sTyr groups=1) <701; RAW_FILE_NAME=P43_V1 SUBJECT_SAMPLE_FACTORS P43 P43_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=8.9; sTyr groups=3) 901-1100; RAW_FILE_NAME=P43_V4 SUBJECT_SAMPLE_FACTORS P43 P43_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=8.7; sTyr groups=1) <701; RAW_FILE_NAME=P43_V6 SUBJECT_SAMPLE_FACTORS P44 P44_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=14.8; sTyr groups=1) <701; RAW_FILE_NAME=P44_V1 SUBJECT_SAMPLE_FACTORS P44 P44_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=15; sTyr groups=2) 701-900; RAW_FILE_NAME=P44_V4 SUBJECT_SAMPLE_FACTORS P44 P44_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=14.9; sTyr groups=2) 701-900; RAW_FILE_NAME=P44_V6 SUBJECT_SAMPLE_FACTORS P46 P46_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=8.8; sTyr groups=1) <701; RAW_FILE_NAME=P46_V1 SUBJECT_SAMPLE_FACTORS P46 P46_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=12.4; sTyr groups=1) <701; RAW_FILE_NAME=P46_V4 SUBJECT_SAMPLE_FACTORS P46 P46_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=2.3; sTyr groups=2) 701-900; RAW_FILE_NAME=P46_V6 SUBJECT_SAMPLE_FACTORS P47 P47_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=12.7; sTyr groups=1) <701; RAW_FILE_NAME=P47_V1 SUBJECT_SAMPLE_FACTORS P47 P47_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=12.1; sTyr groups=3) 901-1100; RAW_FILE_NAME=P47_V4 SUBJECT_SAMPLE_FACTORS P47 P47_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=8.3; sTyr groups=2) 701-900; RAW_FILE_NAME=P47_V6 SUBJECT_SAMPLE_FACTORS P48 P48_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=7.6; sTyr groups=1) <701; RAW_FILE_NAME=P48_V1 SUBJECT_SAMPLE_FACTORS P48 P48_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=13.7; sTyr groups=1) <701; RAW_FILE_NAME=P48_V4 SUBJECT_SAMPLE_FACTORS P48 P48_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=3.7; sTyr groups=2) 701-900; RAW_FILE_NAME=P48_V6 SUBJECT_SAMPLE_FACTORS P49 P49_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=13.8; sTyr groups=None; RAW_FILE_NAME=P49_V1 SUBJECT_SAMPLE_FACTORS P49 P49_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=13.7; sTyr groups=None; RAW_FILE_NAME=P49_V4 SUBJECT_SAMPLE_FACTORS P49 P49_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=9.2; sTyr groups=None; RAW_FILE_NAME=P49_V6 SUBJECT_SAMPLE_FACTORS P50 P50_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=11.6; sTyr groups=None; RAW_FILE_NAME=P50_V1 SUBJECT_SAMPLE_FACTORS P50 P50_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=10; sTyr groups=None; RAW_FILE_NAME=P50_V4 SUBJECT_SAMPLE_FACTORS P50 P50_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=4.6; sTyr groups=None; RAW_FILE_NAME=P50_V6 SUBJECT_SAMPLE_FACTORS P52 P52_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=12.2; sTyr groups=1) <701; RAW_FILE_NAME=P52_V1 SUBJECT_SAMPLE_FACTORS P52 P52_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=11.4; sTyr groups=2) 701-900; RAW_FILE_NAME=P52_V4 SUBJECT_SAMPLE_FACTORS P52 P52_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=6.4; sTyr groups=2) 701-900; RAW_FILE_NAME=P52_V6 SUBJECT_SAMPLE_FACTORS P55 P55_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=11.3; sTyr groups=1) <701; RAW_FILE_NAME=P55_V1 SUBJECT_SAMPLE_FACTORS P55 P55_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=12.4; sTyr groups=1) <701; RAW_FILE_NAME=P55_V4 SUBJECT_SAMPLE_FACTORS P55 P55_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=11; sTyr groups=1) <701; RAW_FILE_NAME=P55_V6 SUBJECT_SAMPLE_FACTORS P60 P60_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=10; sTyr groups=1) <701; RAW_FILE_NAME=P60_V1 SUBJECT_SAMPLE_FACTORS P60 P60_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=8.9; sTyr groups=2) 701-900; RAW_FILE_NAME=P60_V4 SUBJECT_SAMPLE_FACTORS P60 P60_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=7; sTyr groups=1) <701; RAW_FILE_NAME=P60_V6 SUBJECT_SAMPLE_FACTORS P61 P61_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=12.1; sTyr groups=None; RAW_FILE_NAME=P61_V1 SUBJECT_SAMPLE_FACTORS P61 P61_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=11.8; sTyr groups=None; RAW_FILE_NAME=P61_V4 SUBJECT_SAMPLE_FACTORS P61 P61_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=11.4; sTyr groups=None; RAW_FILE_NAME=P61_V6 SUBJECT_SAMPLE_FACTORS P62 P62_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=14.9; sTyr groups=1) <701; RAW_FILE_NAME=P62_V1 SUBJECT_SAMPLE_FACTORS P62 P62_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=16.6; sTyr groups=2) 701-900; RAW_FILE_NAME=P62_V4 SUBJECT_SAMPLE_FACTORS P62 P62_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=11.8; sTyr groups=3) 901-1100; RAW_FILE_NAME=P62_V6 SUBJECT_SAMPLE_FACTORS P63 P63_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=5; sTyr groups=None; RAW_FILE_NAME=P63_V1 SUBJECT_SAMPLE_FACTORS P63 P63_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=6.1; sTyr groups=None; RAW_FILE_NAME=P63_V4 SUBJECT_SAMPLE_FACTORS P63 P63_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=10.3; sTyr groups=None; RAW_FILE_NAME=P63_V6 SUBJECT_SAMPLE_FACTORS P64 P64_V1 Treatedrial arm:Treated Time point=Baseline; 24h Creatinine=6.1; sTyr groups=1) <701; RAW_FILE_NAME=P64_V1 SUBJECT_SAMPLE_FACTORS P64 P64_V4 Treatedrial arm:Treated Time point=24 months; 24h Creatinine=8.2; sTyr groups=2) 701-900; RAW_FILE_NAME=P64_V4 SUBJECT_SAMPLE_FACTORS P64 P64_V6 Treatedrial arm:Treated Time point=48 months; 24h Creatinine=4; sTyr groups=2) 701-900; RAW_FILE_NAME=P64_V6 SUBJECT_SAMPLE_FACTORS P65 P65_V1 Treatedrial arm:Untreated Time point=Baseline; 24h Creatinine=10.3; sTyr groups=None; RAW_FILE_NAME=P65_V1 SUBJECT_SAMPLE_FACTORS P65 P65_V4 Treatedrial arm:Untreated Time point=24 months; 24h Creatinine=9.5; sTyr groups=None; RAW_FILE_NAME=P65_V4 SUBJECT_SAMPLE_FACTORS P65 P65_V6 Treatedrial arm:Untreated Time point=48 months; 24h Creatinine=13.4; sTyr groups=None; RAW_FILE_NAME=P65_V6 #COLLECTION CO:COLLECTION_SUMMARY Serum and urine samples were collected at the three study sites; Liverpool, CO:COLLECTION_SUMMARY Paris and Piešťany. Samples collected at Paris and Piešťany were transported CO:COLLECTION_SUMMARY frozen to the Royal Liverpool University Hospital for metabolite analysis and CO:COLLECTION_SUMMARY storage at -80 °C. Urine was collected over 24-h into 2.5 L bottles containing CO:COLLECTION_SUMMARY 30 mL of 5 mol/L sulphuric acid which was subsequently aliquoted and stored at CO:COLLECTION_SUMMARY -80 °C. CO:SAMPLE_TYPE Urine CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY Samples studied were from patients partaking in the SONIA 2 clinical trial of TR:TREATMENT_SUMMARY nitisinone in AKU. SONIA 2 was a 4-year, open-label, evaluator-blind, TR:TREATMENT_SUMMARY randomised, no treatment controlled, parallel-group study undertaken at three TR:TREATMENT_SUMMARY study sites; Liverpool (UK), Paris (France) and Piešťany (Slovakia). The TR:TREATMENT_SUMMARY details and outcomes of the trial are published (1). Serum and urine samples TR:TREATMENT_SUMMARY were collected from participants at baseline (pre-treatment) then at 3 months TR:TREATMENT_SUMMARY and 1, 2, 3 and 4 years on 10 mg oral daily nitisinone (Orfadin®) treatment or TR:TREATMENT_SUMMARY no treatment. The serum and urine samples from visit 1 (baseline; TR:TREATMENT_SUMMARY pre-treatment), visit 4 (2 years), visit 6 (4 years) underwent metabolomic TR:TREATMENT_SUMMARY analysis. In this study, only the data from patients with samples available for TR:TREATMENT_SUMMARY these three time points were included; 53 and 50 patients in treated and TR:TREATMENT_SUMMARY untreated groups respectively for urine, and 47 and 45 patients in treated and TR:TREATMENT_SUMMARY untreated groups respectively for serum. Reference: (1) Ranganath, L.R.; TR:TREATMENT_SUMMARY Psarelli, E.E.; Arnoux, J.B.; Braconi, D.; Briggs, M.; Bröijersén, A.; Loftus, TR:TREATMENT_SUMMARY N.; Bygott, H.; Cox, T.F.; Davison, A.S.; et al. Efficacy and Safety of TR:TREATMENT_SUMMARY Once-Daily Nitisinone for Patients with Alkaptonuria (SONIA 2): An TR:TREATMENT_SUMMARY International, Multicentre, Open-Label, Randomised Controlled Trial. Lancet TR:TREATMENT_SUMMARY Diabetes Endocrinol. 2020, 8, 762–772, doi:10.1016/S2213-8587(20)30228-X. TR:TREATMENT_PROTOCOL_ID Clinical trial ID: EudraCT no. 2013-001633-41 TR:TREATMENT_COMPOUND Nitisinone (NTBC) TR:TREATMENT_DOSE 10 mg daily TR:TREATMENT_DOSEDURATION 48 months total #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Prior to analysis, urine samples were thawed at room temperature before SP:SAMPLEPREP_SUMMARY vortexing and centrifugation at 1500 ×g for 5 minutes. 150 µL of each urine SP:SAMPLEPREP_SUMMARY sample was aliquoted into a 1 mL 96-well plate (Waters Corporation, Wilmslow, SP:SAMPLEPREP_SUMMARY UK) and diluted with 450 µL of deionised water. Samples were mixed on a plate SP:SAMPLEPREP_SUMMARY shaker (MTS 2/4m IKA) at 600 rpm for 10 min and sub-aliquoted into multiple SP:SAMPLEPREP_SUMMARY replicate 96-well plates before storage at -80 °C ready for analysis. Prior to SP:SAMPLEPREP_SUMMARY analysis, sample plates were thawed then agitated on a plate shaker (MTS 2/4m SP:SAMPLEPREP_SUMMARY IKA) at 600 rpm for 10 min. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Analysis of serum and urine samples was performed using a published LC-QTOF-MS CH:CHROMATOGRAPHY_SUMMARY acquisition method, which employed a 1290 Infinity II HPLC coupled to a 6550 CH:CHROMATOGRAPHY_SUMMARY QTOF-MS equipped with dual AJS electrospray ionisation source (Agilent, Cheadle, CH:CHROMATOGRAPHY_SUMMARY UK). Data acquisition parameters are detailed in brief below and in full in CH:CHROMATOGRAPHY_SUMMARY Supplementary Materials. Reversed-phase LC was performed on an Atlantis dC18 CH:CHROMATOGRAPHY_SUMMARY column (3×100 mm, 3 μm, Waters, Manchester, UK) maintained at 60 °C. Mobile CH:CHROMATOGRAPHY_SUMMARY phase composition was (A) water and (B) methanol, both with 5 mmol/L ammonium CH:CHROMATOGRAPHY_SUMMARY formate and 0.1 % formic acid. The elution gradient began at 5 % B 0–1 min and CH:CHROMATOGRAPHY_SUMMARY increased linearly to 100 % B by 12 min, held at 100 % B until 14 min, then at 5 CH:CHROMATOGRAPHY_SUMMARY % B for a further 5 min. MS data acquisition was performed in positive and CH:CHROMATOGRAPHY_SUMMARY negative ionisation polarity with mass range 50–1700 in 2 GHz mode with CH:CHROMATOGRAPHY_SUMMARY acquisition rate at 3 spectra/second. Sample injection volume was 1 and 2 µL in CH:CHROMATOGRAPHY_SUMMARY negative and positive polarities, respectively. CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent 1290 Infinity II CH:COLUMN_NAME Waters Atlantis dC18 (3x100 mm, 3 µm) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 6550 QTOF MS:INSTRUMENT_TYPE QTOF MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS MS acquisition conditions detailed in attached Supplementary Materials. Raw data MS:MS_COMMENTS were mined using the targeted feature extraction function in Masshunter MS:MS_COMMENTS Profinder (build 10.00, Agilent) with mass targets based on chemical formulae of MS:MS_COMMENTS known/predicted phe-tyr pathway metabolites from the customised compound MS:MS_COMMENTS databases described below. A combined compound database was compiled using PCDL MS:MS_COMMENTS Manager (Agilent, build 08.00). Accurate mass retention time (AMRT) matched MS:MS_COMMENTS metabolites were present in our published AMRT database, which was generated MS:MS_COMMENTS from chemical standards using the same LC-QTOF-MS methodology employed here: MS:MS_COMMENTS phenylalanine, phenylethylamine, tyrosine, N-acetyl-tyrosine, tyramine, HPPA, MS:MS_COMMENTS HPLA and HGA. Other established phenylalanine metabolites added to the database MS:MS_COMMENTS for mining by accurate mass alone were hydroxyphenylacetic acid, MS:MS_COMMENTS phenylacetaldehyde, phenylacetamide, phenylacetic acid, phenylacetylglutamine, MS:MS_COMMENTS phenylethylamine, phenyllactic acid and phenylpyruvic acid. The remaining MS:MS_COMMENTS formulae were from non-established but theoretically possible phase 1 and 2 MS:MS_COMMENTS biotransformation products derived from phenylalanine (n=74), tyrosine (n=74), MS:MS_COMMENTS HPPA (n=67) and HPLA (n=67) predicted using the Biotransformation Mass Defects MS:MS_COMMENTS tool (Agilent), in addition to the HGA biotransformation products (n=7) MS:MS_COMMENTS previously established by our group. Feature extraction parameters were accurate MS:MS_COMMENTS mass match window ±5 ppm with addition of matched retention time (RT; window MS:MS_COMMENTS ±0.3 min) for AMRT database metabolites. Allowed ion species were: H+, Na+, and MS:MS_COMMENTS NH4+ in positive polarity, and H− and CHO2- in negative polarity. Charge state MS:MS_COMMENTS range was 1–2, and dimers were allowed. ‘Find by formula’ filters were: MS:MS_COMMENTS score >60 in at least 60 % of samples in at least one sample group. Where MS:MS_COMMENTS compounds were detected in both positive and negative ionisation, the polarity MS:MS_COMMENTS with the clearest signal was selected for further analysis. Extracted peak area MS:MS_COMMENTS intensity data were exported in .csv file format and imported into Mass Profiler MS:MS_COMMENTS Professional (MPP; build 15.1, Agilent), in which all statistical analyses were MS:MS_COMMENTS performed unless stated otherwise. In MPP, all data were log2 transformed and MS:MS_COMMENTS pareto scaled. Urine data were normalised to 24-h creatinine values. QC was MS:MS_COMMENTS performed based on compound signal intensity data from the pooled samples MS:MS_COMMENTS interspersed throughout each analytical sequence. Compounds were retained for MS:MS_COMMENTS subsequent statistical analyses if a) observed in 100 % of replicate injections MS:MS_COMMENTS for at least one sample group pool, and b) peak area coefficient of variation MS:MS_COMMENTS (CV) remained <30% across replicate injections for each sample group pool across MS:MS_COMMENTS batches 1 and 2 combined. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS peak area (pareto-scaled, log2-transformed, 24h creatinine normalised) MS_METABOLITE_DATA_START Samples F01_V1 F01_V4 F01_V6 F02_V1 F02_V4 F02_V6 F03_V1 F03_V4 F03_V6 F04_V1 F04_V4 F04_V6 F05_V1 F05_V4 F05_V6 F06_V1 F06_V4 F06_V6 F07_V1 F07_V4 F07_V6 F08_V1 F08_V4 F08_V6 F09_V1 F09_V4 F09_V6 F10_V1 F10_V4 F10_V6 F11_V1 F11_V4 F11_V6 F12_V1 F12_V4 F12_V6 F13_V1 F13_V4 F13_V6 F14_V1 F14_V4 F14_V6 F15_V1 F15_V4 F15_V6 F16_V1 F16_V4 F16_V6 F17_V1 F17_V4 F17_V6 F18_V1 F18_V4 F18_V6 F20_V1 F20_V4 F20_V6 F21_V1 F21_V4 F21_V6 F23_V1 F23_V4 F23_V6 F24_V1 F24_V4 F24_V6 F25_V1 F25_V4 F25_V6 F26_V1 F26_V4 F26_V6 F29_V1 F29_V4 F29_V6 F31_V1 F31_V4 F31_V6 F32_V1 F32_V4 F32_V6 L01_V1 L01_V4 L01_V6 L03_V1 L03_V4 L03_V6 L06_V1 L06_V4 L06_V6 L07_V1 L07_V4 L07_V6 L08_V1 L08_V4 L08_V6 L09_V1 L09_V4 L09_V6 L10_V1 L10_V4 L10_V6 L11_V1 L11_V4 L11_V6 L12_V1 L12_V4 L12_V6 L13_V1 L13_V4 L13_V6 L14_V1 L14_V4 L14_V6 L15_V1 L15_V4 L15_V6 L16_V1 L16_V4 L16_V6 L17_V1 L17_V4 L17_V6 L18_V1 L18_V4 L18_V6 L21_V1 L21_V4 L21_V6 L22_V1 L22_V4 L22_V6 L23_V1 L23_V4 L23_V6 L24_V1 L24_V4 L24_V6 L28_V1 L28_V4 L28_V6 L29_V1 L29_V4 L29_V6 L30_V1 L30_V4 L30_V6 L31_V1 L31_V4 L31_V6 L33_V1 L33_V4 L33_V6 L35_V1 L35_V4 L35_V6 L37_V1 L37_V4 L37_V6 L38_V1 L38_V4 L38_V6 L40_V1 L40_V4 L40_V6 P01_V1 P01_V4 P01_V6 P02_V1 P02_V4 P02_V6 P03_V1 P03_V4 P03_V6 P05_V1 P05_V4 P05_V6 P06_V1 P06_V4 P06_V6 P07_V1 P07_V4 P07_V6 P09_V1 P09_V4 P09_V6 P11_V1 P11_V4 P11_V6 P12_V1 P12_V4 P12_V6 P13_V1 P13_V4 P13_V6 P15_V1 P15_V4 P15_V6 P16_V1 P16_V4 P16_V6 P17_V1 P17_V4 P17_V6 P18_V1 P18_V4 P18_V6 P20_V1 P20_V4 P20_V6 P21_V1 P21_V4 P21_V6 P22_V1 P22_V4 P22_V6 P23_V1 P23_V4 P23_V6 P24_V1 P24_V4 P24_V6 P26_V1 P26_V4 P26_V6 P28_V1 P28_V4 P28_V6 P29_V1 P29_V4 P29_V6 P30_V1 P30_V4 P30_V6 P31_V1 P31_V4 P31_V6 P32_V1 P32_V4 P32_V6 P33_V1 P33_V4 P33_V6 P34_V1 P34_V4 P34_V6 P35_V1 P35_V4 P35_V6 P37_V1 P37_V4 P37_V6 P39_V1 P39_V4 P39_V6 P40_V1 P40_V4 P40_V6 P41_V1 P41_V4 P41_V6 P42_V1 P42_V4 P42_V6 P43_V1 P43_V4 P43_V6 P44_V1 P44_V4 P44_V6 P46_V1 P46_V4 P46_V6 P47_V1 P47_V4 P47_V6 P48_V1 P48_V4 P48_V6 P49_V1 P49_V4 P49_V6 P50_V1 P50_V4 P50_V6 P52_V1 P52_V4 P52_V6 P55_V1 P55_V4 P55_V6 P60_V1 P60_V4 P60_V6 P61_V1 P61_V4 P61_V6 P62_V1 P62_V4 P62_V6 P63_V1 P63_V4 P63_V6 P64_V1 P64_V4 P64_V6 P65_V1 P65_V4 P65_V6 P63_V1 P63_V4 P63_V6 P64_V1 P64_V4 P64_V6 P65_V1 P65_V4 P65_V6 Factors Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial 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arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated 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arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Treated Treatedrial arm:Untreated Treatedrial arm:Untreated Treatedrial arm:Untreated Phenylalanine 0.5902948 1.1542768 1.7299829 0.76134044 0.8696739 1.1084139 -0.27508375 -0.11773339 -0.28722748 0.65372235 0.4842012 0.31910104 0.47537675 1.527795 1.9512138 -0.09325991 -1.1236973 1.0176482 0.6357317 0.9339678 1.7498192 0.80970395 0.26359814 0.72246903 0.9776529 1.8976696 1.8617772 -0.37723964 0.36210886 1.300787 -1.1600459 0.13949005 -0.51207346 0.74080145 1.343833 0.7722458 -0.16972144 -0.010393477 1.3499295 -2.1981122 -2.431545 0.09620563 0.8214789 -0.31568158 2.2942448 1.2649678 -0.19801973 1.8737794 0.40856314 2.0552902 0.7183072 0.40318996 -0.7829604 1.5102589 1.5223471 2.6839175 2.4122753 1.1974277 1.4922428 2.1910126 0.22065869 0.40305322 1.3314396 1.2767618 1.3769035 1.6256523 0.5803607 0.77308834 1.35102 0.4992684 -0.020987255 1.2427788 1.218903 2.5959067 2.297607 0.3017526 0.43181732 1.1720878 -0.76604277 -1.1205035 0.90391773 -0.3944927 -0.6521231 -0.4789997 0.6243335 0.8675914 0.09362078 -0.54244316 -0.7339006 0.15714529 -1.2576807 -0.111806974 0.9917551 0.07448393 0.30329302 0.4391061 0.17482279 -0.090675056 -0.503284 0.23019055 1.8403655 0.32528022 -0.47059494 -0.17792907 0.98215175 -0.9970536 -0.89640474 0.17971271 -1.2213718 -0.07432337 0.44643623 0.47091764 -0.4509478 0.8806651 0.47467571 0.08269633 0.59269047 -0.14921744 0.49036288 0.24610983 0.13065925 -0.78661036 -0.42386246 -1.2688626 -0.66556245 0.25118098 -0.27860177 -0.6394309 -0.8379927 -0.06767523 0.47551826 0.64777523 -0.1287834 -0.3214681 -0.62301403 1.382892 -0.7079455 1.2559654 0.22558518 0.89611065 0.42866653 -0.33389163 -0.9024679 -0.5128095 0.50463045 0.512358 0.84190977 -0.20420526 0.009776672 0.13815948 1.6347518 0.7562216 1.653178 1.0814191 -0.21343508 0.82570595 -0.24844034 -0.87343836 -1.1483425 0.6195787 -0.115868665 -0.3690336 0.03005174 0.38706082 0.24831793 -1.2543406 -1.2254351 -1.0857432 -2.4189498 -0.84580296 -0.02888013 -1.504226 -1.0276189 -0.7144983 -1.401982 -0.88094175 -0.29003492 -1.7204971 -1.3623744 -1.3235548 -1.3316972 -1.7372637 -0.6700184 1.5254533 0.60937756 1.1142226 -1.0225191 -0.34268746 0.3135164 0.047675185 0.44075143 -0.06697895 -0.4655508 -0.7017743 0.77518994 -1.4958721 -1.0182444 -0.55834335 -0.9301494 -1.2828281 -1.3044631 -0.54075646 -0.38240775 0.20918898 -0.915726 0.008732237 -0.1381722 -1.5723671 -0.4844031 0.4453743 -1.0138758 -0.7503683 -0.5350749 0.16975482 -0.067533754 0.40264627 -0.66036093 0.015808005 -0.36882216 -0.6100341 -0.83150357 -0.0745507 -0.8571661 -0.40461433 -0.21600245 -0.7216535 -0.9470018 -1.1883887 -0.94560605 -0.97957164 -0.75857437 -1.01541 -0.05333135 -0.15766037 -0.43050104 -0.3072975 0.5399314 -0.56941247 -0.63295126 0.7229014 0.5489514 -0.26561707 -0.60629356 0.52286434 -0.5741863 -0.6906782 -0.17442854 -0.48272118 -0.89155775 -0.8878363 0.5438532 1.3066101 -0.5656544 -0.2995127 -0.080844335 0.025422527 0.27356082 0.6253795 -0.69186884 -0.35497108 0.4250913 0.6150814 0.74818724 1.8015783 -0.40726435 -0.1710552 -0.54018897 -0.6377601 0.23883694 0.30318812 -0.7884258 -0.8288917 1.7896333 0.65930694 1.0852313 1.550286 0.6314776 -0.23175164 1.9568796 -1.5488331 -1.1387105 0.07700202 -0.9024504 -0.78996307 0.4973417 -1.188511 -0.079170376 0.36263028 -0.25067228 -0.0706146 -0.6025291 -0.115218475 0.17003779 0.7852845 -1.6211296 -1.35319 -0.93247354 -0.122303784 -1.0252438 0.28383824 0.27436998 -0.40735498 -0.4626512 -0.77478456 -0.6238359 0.40308025 -0.42572877 -1.2851968 -1.0302657 0.27436998 -0.40735498 -0.4626512 -0.77478456 -0.6238359 0.40308025 -0.42572877 -1.2851968 -1.0302657 Phenylalanine hydrate 0.36643928 0.8275067 2.6331818 -0.7712955 -0.29334626 -0.06699014 -2.3307538 -0.91394025 -0.99147886 -1.5113817 0.10032646 -0.28860673 -1.3964412 0.23283544 0.4590936 -1.4059248 -2.7529416 -0.7409625 0.44006023 0.2606612 2.0336158 -0.5331046 0.38363037 0.2303446 0.40960932 1.3547987 0.8896621 -0.17417508 0.268376 0.59437734 -0.49167252 0.59048146 1.1183766 -0.6072181 0.43519098 0.17139487 -1.195371 -1.1429859 0.54529405 -1.1992198 -2.7173195 0.03623175 -0.011334043 1.1254075 1.6102451 0.034346823 1.2917815 2.8778791 -0.2554255 2.8863332 1.5192535 0.3653281 -0.43142202 2.7908804 -0.08838739 1.7813996 2.0966275 -0.09978675 -0.12716171 1.0123926 0.24052572 -0.10711329 -0.03279117 -0.38761973 0.38667366 1.7590082 -0.67899036 -0.81592596 0.13642305 0.2997902 0.17571986 1.52038 -0.046748508 1.2859527 1.218724 -0.62746876 -0.066237256 0.8755995 -0.58629704 -0.6021375 2.6356199 -0.9652369 -0.71623987 -0.8348196 0.30108824 0.112285495 1.1136788 -0.0840225 0.8362637 2.1029 -0.58294624 1.2985168 1.4180071 -1.0555147 0.15681255 0.22307338 1.0871375 0.5766012 0.4918512 0.25508898 1.5938023 1.3939586 0.29705262 0.53916395 0.6526495 0.02465007 0.8071417 1.0686202 -1.1639241 0.036689825 -0.06962704 -0.60378474 0.030481728 1.243432 -0.9655598 -0.5740795 0.013560033 -1.213784 0.49856728 0.61246014 -0.18741038 -0.9440864 -0.16182601 -1.0266021 0.78112376 1.005517 0.23143944 -0.7563413 -0.38959628 -0.971289 0.48130998 2.35302 -0.25107968 0.045887683 0.8515146 -0.027783146 -0.6137119 -0.031169299 -0.5999351 0.099143624 0.1330868 0.1197617 -0.0677793 0.40889364 -0.29727486 0.47223818 1.2269123 -0.07151015 0.34907764 1.1664313 -0.4272948 1.2512802 1.8889846 -0.45296624 0.32105866 0.31447867 -0.48959348 -0.9267075 -0.474505 0.3910821 0.2310748 0.3881776 0.13267316 0.26066032 0.70140266 -0.560622 -0.5973998 -0.98755664 -0.9820924 0.5021067 1.8616486 -1.0953239 0.23254246 0.4562118 -0.63366693 -0.759985 -0.17986251 -1.2149732 -1.0337664 -1.1075733 -1.3045715 0.3740597 0.91337967 -0.7606454 -0.18453945 -0.400543 -0.33890375 0.32003185 0.47069433 -0.6093071 -1.5668002 -1.6139922 -0.6011007 -0.73712283 0.4332997 -0.7159496 0.60151523 -0.002125303 -0.16417445 -0.94801855 -0.6337168 -0.8750516 -0.55134064 0.084134065 -1.2861413 -0.27006862 0.6833181 0.062909156 -0.76699495 -0.10946173 -1.0780911 0.078583606 -0.125587 -0.749275 1.0854149 1.5817544 -0.86718994 0.27796933 0.69128233 -0.48999986 -0.3138836 -0.54749644 -0.85174406 0.29958975 0.26260784 -0.8480903 -0.4276567 -0.94074285 -0.09183795 0.19148229 -0.22855943 -1.2442548 -0.2161505 -0.55443203 -0.77241933 0.4028842 0.61948097 -0.027170863 -1.047945 -0.84688026 -0.8225132 -0.98056394 -1.6547422 -1.2308363 0.17791228 -0.88852185 0.3510841 0.2936973 -0.7142561 -1.3819696 -0.43162158 0.7252581 -0.4517698 1.291359 2.5536003 -0.34614867 0.22471975 -0.26735008 -0.7424021 -0.13208355 0.09175178 -0.22314413 -0.88996416 1.2121285 -0.17896722 1.0062916 1.3624518 -1.3684386 -0.4718581 0.25555342 -1.0390157 0.5064989 2.710489 -0.3430292 0.47839096 0.72370064 0.0765599 0.19863647 2.6632843 -1.2747928 -1.8884884 -0.78024024 -0.494499 -0.99395883 0.69949144 -0.96274877 0.2767203 1.6492834 -1.5250361 -0.45701185 0.50002044 0.016598772 1.1816785 1.4112974 -1.0691046 -0.8802955 -1.1796558 -1.1154884 0.012201218 0.52309215 0.7288248 0.37343836 -0.7843811 -0.49851194 -0.2813836 1.3770431 -0.3806506 -0.34659678 -0.902813 0.7288248 0.37343836 -0.7843811 -0.49851194 -0.2813836 1.3770431 -0.3806506 -0.34659678 -0.902813 Phenylpyruvic acid -0.68338335 3.2511811 3.2723067 -0.72409284 -0.7833697 0.30037627 -1.123565 -0.89064074 -0.8289867 -0.46192795 2.483766 1.2189268 -0.47479317 2.7428555 3.079808 -1.1444515 -1.3744137 -0.36085483 -0.93732166 -0.8012796 -0.03649338 0.4871854 2.24291 2.2820485 -0.6485328 3.0816817 2.896181 -0.6039622 0.15637441 0.54509526 -1.3817034 2.845745 2.4697406 -1.2577302 -0.24962088 -0.7061411 -1.924417 -1.0807059 -0.5158325 -1.5247128 -2.071564 -0.8009876 -0.77460366 3.0882614 3.6585655 -0.48713696 2.2901974 3.3487344 -0.15789476 3.793292 3.2202022 -1.1058766 -1.6262821 0.020494686 -0.64109796 3.5484219 3.2461243 -0.72068703 -0.43898204 -0.24555704 -0.68925744 -0.7515539 -0.40518796 -0.62542003 2.7564545 3.033182 -0.9095273 -1.3639877 -0.53320324 -0.7038513 2.2917929 2.9312062 -1.3759462 2.9745443 2.6868513 -0.37614655 2.4504304 2.3952532 -0.51389056 2.3247514 3.439677 -0.977416 -0.7559914 -0.96346915 -0.51137173 -0.4216294 -0.7760383 -0.8883927 2.5857852 3.1116207 -1.4103651 2.5837753 2.8413074 -1.0106267 2.6044772 2.5224237 -0.95518214 -0.89399856 -1.4520094 -1.1803362 3.2635283 2.4358058 -1.6633589 -1.3793615 -0.8990417 -1.370536 1.9854033 2.9106948 -1.8004494 -1.1402373 -1.3456658 -1.1817371 2.2501874 2.7051792 -0.85420483 -1.1853127 -0.875941 -1.3214281 2.5071166 2.7079225 -1.1012766 -1.7012073 -1.5185664 -1.7047154 2.4310193 2.5222735 -1.9032456 -1.4935248 -1.4503838 -1.1588078 2.3195496 2.6228566 -1.2891346 -0.9672859 -0.83863324 -0.6200653 -1.6313046 -0.5390643 -1.421425 2.8241556 2.9621143 -0.93846786 -1.2905601 -1.5374726 -0.6369736 2.3264942 3.2822285 -0.6418085 -0.7549405 -0.57992554 -0.49132437 2.639011 2.9585028 -1.6829641 -1.6342076 -0.8556818 -1.4240391 -1.8495145 -1.8934801 -0.8726794 -1.863188 -0.7307849 -0.7234327 2.5606096 2.2569647 -2.4605124 -1.476927 -2.0731 -1.9935436 2.3983977 2.548348 -2.5791857 1.8634084 2.283278 -1.195336 -0.8829356 -0.22388591 -1.4458725 -1.5183395 -1.311371 -2.172802 2.275693 2.5673332 -0.87472725 -1.5783824 -1.4012516 -1.3082824 2.3724546 2.2842855 -1.1298743 -0.8666772 -1.3398249 -1.459052 -1.5674741 -1.1614461 -2.214841 1.9638678 1.8300147 -1.8736595 -1.6576335 -2.0988686 -1.6108583 -1.6202819 -1.2890887 -1.8119748 2.264368 2.1657913 -1.788441 -1.714777 -1.3137451 -1.6628845 -1.804953 -1.3948349 -1.3296067 2.2785792 2.6758332 -1.4111936 2.2399452 2.029549 -1.443204 -1.75307 -1.376267 -1.6915169 2.5513897 2.568725 -1.9064608 -2.0483942 -1.8948244 -2.1256783 -1.7909617 -1.8342879 -1.7875792 2.2391632 -0.24841267 -1.7029389 2.5828948 2.8689582 -2.439856 -1.8524796 -0.859079 -1.8009043 -2.0226626 -2.7257977 -1.1001759 1.8104993 1.8925618 -0.5983074 -0.9828489 -1.0256113 -2.3422034 -1.2853103 -0.66836643 -1.5275387 2.0843847 2.4033537 -1.1477796 -0.35741124 -1.1094245 -1.6105754 -1.4574888 -0.6502483 -0.7453207 -0.7590724 -0.05406991 -1.5128909 2.514655 2.0573196 -1.4153229 2.5612478 2.3815434 -1.0517108 1.8008841 3.5197334 -0.90090597 2.7514956 3.1567774 -1.3004926 0.3735945 2.8971384 -1.32959 -1.0189278 -0.3369549 -2.137487 -1.8096864 -1.5360507 -1.5696903 2.5024157 2.739367 -1.3431022 2.612507 2.3480988 -2.0168955 2.153456 2.5363576 -1.5555005 -1.7198598 -1.5660018 -1.2102717 1.9773599 2.2633698 -1.4051616 -1.2718354 -2.0815573 -0.9504587 2.6024117 3.045268 -1.4356118 -2.6279552 -1.5032111 -1.4051616 -1.2718354 -2.0815573 -0.9504587 2.6024117 3.045268 -1.4356118 -2.6279552 -1.5032111 Phenylacetamide 0.14174484 2.7940364 3.0771916 -0.2476078 -0.38187933 0.5207483 -1.2439876 -1.3526055 -0.62566924 0.004324696 1.8010789 -0.06718532 -0.7836352 1.2665305 1.6990689 -0.70633197 -1.0338784 0.06475866 -1.1811416 -1.0743206 0.29241464 -0.45478123 1.7881835 2.5178142 0.35911983 2.199076 1.7650149 -0.78877187 -0.3672652 0.30810502 -1.2141322 1.4034979 0.7946494 -0.53704536 0.09768314 -0.5880714 -0.774453 -0.95634955 0.8264618 -1.5691706 -2.4033258 -0.4839216 0.669234 2.770214 3.9394424 0.6889622 1.7294528 3.3824215 0.0819773 3.4928994 2.2469456 -0.13751785 -0.7793035 0.6007207 0.0291221 4.223451 3.5640292 -0.581029 -0.25575948 0.40987524 -0.2777738 -0.79047024 0.25087804 -0.28153965 2.3722212 1.9067864 0.05580277 -1.4910934 -0.50135046 -0.16077435 1.6747094 2.5597692 -0.81898636 2.363669 2.265417 -0.19103104 0.7833505 1.2955921 -0.8008497 1.5442642 3.0824666 -1.0227715 -1.2769 -1.0266259 -0.34721217 -0.2470651 -0.3316399 -0.7777408 0.39852363 1.1246387 -0.97971505 0.9483195 1.9277533 -0.6359685 0.5024302 0.3684012 0.64627624 0.08501837 0.39230582 -0.8893555 2.1466482 0.77693164 -1.3949329 -0.98497117 -0.24192354 -0.9712899 -0.33905557 1.1289029 -0.6238415 -0.47832593 -0.5369111 -0.22844964 0.20766692 1.4230666 -0.026781196 -0.42713606 0.2375166 -0.68498904 1.5218484 0.92567253 -0.2544182 -0.83940285 -0.1475036 -1.4472917 1.2750955 1.8610665 -0.86753166 -1.6017218 -0.95087695 -0.7887149 1.5560166 1.5256474 -0.8079356 -0.66986877 -0.47229934 0.04682298 -1.4707965 -0.046186086 -0.51568127 2.1489398 2.219188 -0.4939467 -1.0108624 -0.3468206 -0.41542593 1.413859 2.2204435 -0.55636656 -0.29424098 -0.16526775 0.02142313 1.9248458 2.5018666 -0.9906997 -1.5220376 -0.3637714 -1.2723131 -1.4846787 -1.6645318 0.08459939 -0.6530796 -0.56616324 -0.43286952 1.6679201 1.5884355 -1.5392183 -1.2127748 -1.2369255 -2.1106896 0.8824445 1.1498579 -2.0227096 0.14125697 1.0459999 -0.88471794 -0.88807887 0.38616043 -1.7850046 -1.183086 -1.3150117 -0.9728681 2.1568413 1.7179465 0.39264256 -0.46279162 -0.67796135 -1.0537705 1.279118 1.8634622 -0.29723775 -0.06988052 -0.6528547 -0.8712497 -1.1488414 -0.3567234 -1.8812236 -0.56707287 -0.27565786 -1.724861 -2.2561758 -1.6574023 -1.4792223 -1.51163 -0.40063888 -1.4825635 1.1925235 1.2501975 -0.75408643 -1.3242545 -0.56409156 -1.4700414 -0.8142329 -0.7173026 -0.26854938 1.0146803 1.9611094 -1.4593365 0.70534855 0.53176814 -0.74024343 -1.0908495 -0.603153 -1.8104038 0.6157552 0.9717974 -1.432639 -1.4961766 -1.6539029 -1.519606 -1.1502248 -0.8957863 -1.8682817 0.3915867 -1.0682005 -1.3277624 1.5144054 2.5771382 -2.0990956 -1.4901325 -0.89313745 -1.7204126 -1.8179481 -2.4941704 -0.5987334 1.3771048 1.705816 -0.6381372 -0.604966 -0.97237384 -2.644871 -1.311821 -0.49896315 -0.8996695 0.16441856 0.5603841 -0.33515194 0.643141 0.07951408 -1.3759189 -1.3439132 -0.9221534 -0.23152655 0.19683269 1.0283264 -0.41729304 2.6246142 2.3205793 -0.73255575 1.8567193 2.0487676 -1.0227342 0.38763526 2.9413307 -0.9135483 1.5083029 1.3054436 -0.8708237 -1.0422016 2.114314 -0.704209 -0.27948907 0.72682226 -1.3101676 -1.2492169 -0.37959817 -1.4363345 1.396194 1.7210903 0.16232018 2.1641986 1.7909153 -1.7077063 0.020080449 0.70345896 -1.4892635 -1.6398082 -1.1274295 -1.1848934 0.98369455 1.9376118 -0.5323811 -0.8404573 -1.1099726 -0.0728056 2.2078912 3.2759714 -0.9099484 -1.0618147 -1.435084 -0.5323811 -0.8404573 -1.1099726 -0.0728056 2.2078912 3.2759714 -0.9099484 -1.0618147 -1.435084 Phenylacetylglutamine -0.2983719 1.060994 1.9846649 0.5236139 0.13289835 0.8864495 -0.034782715 0.36870432 0.3783243 0.51021475 0.35847303 0.27098855 -0.0352252 0.9226892 1.267881 0.441159 -0.40315926 1.6746179 0.53848636 0.5559662 2.1338434 -0.21686262 -0.9336907 -0.14210044 0.6612485 1.5314637 0.39392275 -0.004128235 1.3885536 1.6702849 1.030764 1.2202318 0.5993102 0.38618907 1.3594791 1.1310626 -0.34509847 0.12851445 1.0864731 0.04235251 -1.4009335 1.1577675 -0.46847352 -1.1445667 1.5214324 0.27942693 -0.33606192 1.7906493 0.5141955 2.2682724 1.0625526 0.9965254 0.39348683 1.8598443 0.7826963 1.9773327 1.813816 -0.36178023 -0.15303968 1.0841705 0.6696279 0.7494459 1.1444273 0.91410166 0.29771966 1.3077114 0.5372818 -0.16562268 1.0625494 0.7209596 0.29282773 1.2004887 0.10385813 1.0577147 1.3741155 0.47872612 0.3135082 0.72191995 0.4676869 0.44119835 2.4326825 -1.1581936 -1.5762122 -0.33424446 0.40303963 0.305786 0.95765054 0.4612938 0.22969636 0.7759607 0.08514915 0.399131 1.1486539 0.24895108 0.4637422 0.26808125 0.9760629 0.18939076 0.30920464 0.7219167 1.350054 0.7448621 0.23247091 0.7547344 1.3775538 0.5172519 0.17854984 0.7831929 0.0977682 0.8963989 0.32884118 0.30009598 -0.28232768 1.0641472 -1.3839846 -1.6802063 -0.5974977 0.39430624 0.68745846 0.48938513 -0.21230501 -0.56894094 0.23091075 -0.6799657 -0.45458275 0.34844172 0.18513797 0.41000468 0.6897692 0.94449395 0.7468991 1.4065186 0.2566651 0.7516796 1.0980055 0.8263074 -0.1133257 1.26402 -0.021513037 -0.61120164 -0.37292925 0.6322214 -0.56823784 -0.10135071 -0.094793715 0.21396515 0.77312386 0.3649399 0.90492254 1.5071089 0.26840574 0.04952079 1.0774038 -0.42206818 -1.3656214 0.641666 -0.072594 -0.32550943 -0.6046086 0.6372723 -0.35621965 0.28641492 -1.2016834 -1.2251221 -1.6451237 0.015980316 0.17947742 -0.51973313 -2.1376963 -0.1975063 0.5865437 -1.8464894 -1.6752423 -0.3115285 -0.88585466 -0.31729886 0.42023924 -2.3958054 -1.1667336 -1.6805456 -0.24175821 -0.088457964 -0.301643 0.42165026 -1.3569748 0.25091115 -0.7942845 0.13934882 0.68594414 0.2598133 0.36719987 0.041721556 0.09883017 0.3927608 0.59068996 -0.17631283 -0.057123363 -0.13829833 -0.2110218 -0.45002514 0.1885402 -0.93213546 -0.30849338 0.6322525 0.084031455 0.44656718 0.6298418 -1.8465829 -2.0551252 -1.8220199 -0.8163908 0.13824424 0.16708781 0.6547276 0.30722818 0.5732576 -0.42699125 -0.37164602 -1.3307486 -1.5571411 -0.923938 -2.385256 -0.66311187 -0.35099992 0.038107917 -0.49495882 -0.49810046 -0.9344052 -1.1884089 0.28969097 -0.033637166 0.5595012 0.32353136 0.50837433 -0.35824853 -0.0704209 0.20700173 -1.0341089 0.0765813 0.631225 -0.16735986 -0.33414447 -0.5148854 0.17613584 -0.19545774 -0.71691823 -0.35869756 0.26040655 -0.565678 -0.5051114 0.002186211 1.7248844 -2.9229083 -2.260819 -1.4140884 -0.32068142 0.29898646 0.27256674 0.1960805 -0.3596661 0.37970585 0.022497978 -0.27187842 0.37627247 -1.1088908 -0.9287955 -2.4252405 -0.75856274 0.061482675 -0.20093474 -2.0042064 -0.207967 1.634055 -0.637995 0.569662 1.0602664 -2.0631406 -1.7546474 -0.42657825 -0.8962563 -0.62024146 0.32593882 -0.1513484 0.51759773 1.5784377 -1.9644171 -0.7425562 -0.29428956 -1.6577247 -1.1094037 -0.41350034 -0.80023676 -0.2958022 0.4163552 -1.7779139 -0.9723329 -1.5027447 0.009082445 -0.30050075 0.43173406 -0.24313648 -2.137095 -1.1714715 0.6420069 0.5357823 1.79532 -0.8882801 -1.9494659 -0.8924198 -0.24313648 -2.137095 -1.1714715 0.6420069 0.5357823 1.79532 -0.8882801 -1.9494659 -0.8924198 Tyrosine-glucuronide 0.28172943 3.6712518 2.4466987 0.5263473 0.43149573 0.88130414 -0.028639218 -0.54736495 -0.004593331 0.078725465 2.614546 -0.17400005 -0.29565805 3.4178953 1.8331275 -1.6952108 -0.43696356 0.85977185 0.274417 0.3852148 0.21147457 -1.5557972 1.7964593 1.0276438 0.057539754 3.2060952 2.116167 0.50667816 1.2429044 1.4059826 -1.4331387 3.4864893 1.4330773 0.018859494 0.45198324 0.48940593 -1.3748256 0.33061445 0.33848748 -3.5739148 -1.2973564 -0.53875124 -0.8302702 2.5596173 3.7359114 0.9041921 2.54158 2.4118807 0.67086506 3.929968 1.6859859 -1.5065273 -2.8391023 -1.047463 -0.3579013 4.2693286 2.148142 -0.5825502 0.48526105 0.026926434 -0.2566111 0.44419447 1.0859922 0.22557424 3.2445958 1.8683319 -0.107917756 -0.11332824 0.46742496 -0.8901739 2.0078897 1.3490855 -2.1979494 3.5055773 2.0089662 0.55482626 0.37391597 1.739782 -0.205799 2.812308 2.3234959 -0.009480929 0.2320974 -0.554206 -0.18958338 0.15179095 -2.975169 -2.5978878 -0.0551074 -0.2325046 -3.3191102 0.93783206 1.6750045 -3.604236 2.1191835 1.6515039 -2.8087559 -0.65086496 -2.9614577 -0.71301615 2.3572154 1.4485341 0.027851487 -1.0390782 0.6333151 -3.2837105 0.43365115 0.64065665 -0.15417904 -0.07539648 -3.1449716 0.17963086 0.12505817 1.8225862 0.31125095 0.16358602 -0.34878808 -2.4537027 0.79041487 0.1419652 -0.8392335 0.04792301 -0.6535782 -3.5861886 1.5035284 1.3971239 -0.82399553 -0.022387177 -0.47140157 -0.003481404 0.66170853 0.898852 0.21433173 -0.2165752 0.45783034 -0.5324107 -2.2026265 -0.77325183 -3.6101575 2.5727074 1.4964312 -2.6853664 -3.336211 -1.8070142 0.11187501 1.0232983 2.1696467 0.30235577 3.01E-04 -1.4427524 0.5080021 1.379473 1.8157436 -0.3814799 -3.4010124 -1.1213143 -2.9343064 -3.7043598 -3.5358589 0.06791103 -1.0795892 -1.613214 -0.31892803 0.44059888 0.48715895 -3.3693013 -0.054257546 -0.74866897 -1.3243983 -0.91015136 3.0765789 -3.7043598 1.8803606 1.9008763 -0.6372426 -0.23690502 0.8046167 -1.038499 -0.8710325 0.76518893 -1.5341724 1.423026 2.5802472 -3.592252 -3.6885607 -1.0197741 -0.37934104 2.1694002 1.0727788 -0.75779754 0.18473451 -0.60243917 -0.22148569 0.6284408 -0.07663491 -3.7299836 1.50955 2.2392325 -0.6602903 0.26651105 -0.6694495 -3.7644665 -1.0876008 -1.4529471 -3.6832206 2.7306333 1.895341 -3.5861886 -3.7299836 -3.666972 -1.3965694 -1.0212716 -0.72046536 0.26098636 2.2782664 2.327686 -1.4753544 2.8695805 -1.168561 -3.0782902 -2.9457774 -0.9845848 -1.3449738 2.3899686 2.2322993 -2.0896337 -3.666972 -3.888618 -3.408738 -3.2075512 -2.6337516 -0.79940313 2.075803 0.54919946 -3.3932076 2.7736304 3.3660169 -3.3446195 -1.7468134 0.09759351 -0.3479395 -0.76452595 -1.0495552 -3.592252 1.990175 1.4128674 -0.6783173 -0.22918919 -0.51108056 -0.841221 -0.5459364 0.9185654 -1.3334664 2.6327856 2.6037624 -0.2756894 -0.19576776 -0.88365954 -0.049808078 -0.34759492 -0.066619776 -0.21809986 0.5910206 0.6898792 -1.0706662 2.0246706 2.4100366 -0.57731026 2.3848276 2.4827623 0.19143273 -0.36920318 4.353009 -1.0165774 2.2243688 3.259869 -0.579427 0.363176 3.002951 -1.8740412 -0.20230854 -0.014977434 -0.38665697 -1.0427384 0.012355691 -2.052764 2.838603 3.2342749 -0.25466743 2.8384957 2.230743 -2.0541158 2.7609034 2.7824633 -0.3820946 -0.078092165 -0.7335816 -0.70791197 1.3171492 3.035776 -1.2651447 -0.13992545 -0.5520541 0.4117753 0.77596664 3.5124807 0.6221007 0.18333359 0.7519635 -1.2651447 -0.13992545 -0.5520541 0.4117753 0.77596664 3.5124807 0.6221007 0.18333359 0.7519635 Tyramine -0.5606234 4.0664296 -0.27109674 0.78454167 -0.52043355 1.8996713 0.6011308 -0.5323158 0.91813576 1.3307022 -1.2149211 0.37445587 0.70124114 -1.2147387 -0.1315232 -0.20386688 -1.0724956 0.23379596 -0.5879407 -0.028648498 0.2851739 -1.7538482 3.0686057 -2.0522537 -0.126649 0.094236724 -1.348388 -0.28289977 -0.33098733 0.29176506 -0.41513926 1.8378015 -1.6224413 1.2093962 1.9387794 0.9233535 -0.53016895 0.8657961 0.9427205 0.05780091 -1.8647531 0.04820509 1.7188729 3.9226694 5.1012845 0.629652 -1.1718292 -0.13633119 0.9859741 0.72697717 3.839908 -0.13242584 -0.96597916 0.5724031 -0.83362216 0.120293565 -0.34631455 -1.5030951 1.2621859 -0.1962575 -1.0023552 -0.47485194 0.9307966 -0.35558113 -1.022065 -0.7369308 0.5722985 -1.0992504 -0.068636395 -0.6668177 -1.4707588 -0.689553 -0.7158079 -0.45351475 -1.0993706 0.5256409 2.08214 -1.5935766 0.018377976 -1.7535326 -0.5884498 0.44216886 0.38589138 0.5888407 -1.1629913 -1.0129335 -0.9152915 -0.7392471 2.4847393 3.5855489 -1.4153159 2.9057214 -0.7970987 1.0554676 3.0008616 2.968211 -0.24824391 -0.39602554 0.014884336 1.1917657 4.105847 -0.7559445 -0.53060603 -0.019359183 1.0581262 -0.23306476 -1.2631308 3.1744928 0.054002065 0.006684022 -0.21750832 1.3536525 2.7972317 -1.249877 1.2372577 0.9879209 1.2421052 -1.1139641 -1.1316367 2.7940693 -1.0939853 -0.86079395 0.553201 -1.6755115 -1.4872946 -1.418803 -0.4764286 -0.9474674 -0.6836755 0.79030424 -1.1767359 -0.9338578 -0.029288782 -0.5486457 -0.20331037 -0.75624645 -1.1295627 -0.04652321 -0.7667332 3.3931804 2.8194313 -0.70601404 -0.54624814 -0.8338079 0.685082 -1.3596475 3.7611516 0.5912577 -1.002191 0.60847265 1.156104 -1.1856025 -1.0731632 -2.275124 -0.18037833 0.40034452 0.6913875 0.18433173 -0.98601955 0.6966085 -1.4871491 0.09075542 -0.03763131 2.8283393 -1.3575941 -1.0664343 -0.38684857 -1.9383261 -1.5684276 3.3157177 -0.7904906 -0.9168 -1.7364216 -2.56 -0.44602162 -0.7833066 0.5281715 -0.85081697 -0.7182132 0.07824455 -0.7840501 3.3993392 -0.82727516 -1.0164934 -1.9398845 -1.0341039 -1.2974724 3.0925157 -1.4916337 -1.2449249 1.1101698 0.7891659 -0.39137796 -0.16031328 -0.34858802 -1.3756267 2.6276472 -2.2506828 -1.1350863 -1.0213573 -0.94606864 0.97222745 -1.0198832 1.3193303 -1.0034442 -1.5845034 -1.59755 -0.7850677 -1.0302576 -0.91875595 -1.2758709 0.18633635 -1.1590813 0.03953463 -0.8242445 -1.899861 0.029008903 -1.6211984 -1.9779509 1.0838414 -0.7540665 0.8273557 -1.7717295 2.3693554 2.3252435 -1.0393618 -1.258693 -1.6843567 -0.67175037 -0.7247245 0.13634157 -0.34462228 2.5814183 0.7308708 0.6987319 -0.48332238 -1.2067527 -1.3562961 0.83794504 1.8913866 -0.3268125 0.025613317 -1.4080993 -1.1473659 -1.5410167 -2.3070889 0.7087693 0.10280653 -0.8813844 -0.5634566 -1.2609749 1.936726 0.6597811 -0.9007767 0.8566341 1.1380318 0.3867648 -0.07052867 -0.122113764 -0.6729803 -0.5541115 -1.0546864 1.4417428 2.4288902 -0.73999584 3.5847008 -1.4547329 0.47023615 2.9418464 -1.3472574 -0.6459065 -0.7564445 0.601273 -0.9366235 3.0939975 3.2263675 0.82147235 2.0157316 4.1346908 -1.471394 0.94762325 -1.077097 -0.9489097 -0.26023203 0.6453416 -0.097384244 -1.0089581 -0.9189124 -0.40196407 2.0348837 1.8864819 -0.12907572 -1.3808581 -0.42630008 -0.49955156 -2.0679953 0.55401987 -1.0167967 2.1351752 -1.2855979 0.15953857 0.23173809 -0.8337306 0.3581598 2.142869 0.6345262 1.1614691 -0.43812454 -1.2781813 0.15953857 0.23173809 -0.8337306 0.3581598 2.142869 0.6345262 1.1614691 -0.43812454 -1.2781813 HPPA-hydrate -0.061139688 1.82233 2.0763383 -0.6513562 -0.36818048 0.22176002 -0.9644412 -1.0511878 -0.10128872 -0.4772754 1.3205107 -0.01118345 -1.2138381 1.007605 2.1250007 -1.2318358 -2.9644132 -0.89440477 -0.8974075 -0.6303866 1.6878219 -0.64903235 0.11623281 2.0550137 -0.025451126 1.1685652 1.8354224 0.53262925 0.72689116 0.62524325 0.012428925 1.0290824 1.836835 -0.41188917 0.7667383 0.29188037 -0.8994916 -0.79271245 0.3988847 -1.2452656 -2.2570195 0.45532018 -0.4624193 0.17302424 3.4639838 -0.13229565 -0.48862514 1.713759 0.14665937 2.596265 1.0646571 -0.48797777 -1.8534096 1.5535939 0.30348113 2.5105824 2.0420873 -0.034451965 -0.3437496 0.98049754 0.08048774 -0.02985509 -0.13493997 0.19953921 0.90026164 2.9277635 -0.38704342 -1.045226 0.063071266 0.068013616 0.07639616 0.82684153 -0.74627715 2.153324 1.59638 0.06954887 1.272068 1.6140046 -0.08975576 -0.2302483 1.9712875 -0.4924189 -0.9242276 -0.9279979 0.007461553 0.18102579 0.61090934 -0.58593285 -0.4832784 1.1931639 -1.2148092 1.1360407 1.8620803 -1.1758717 2.0334942 1.5556885 0.53872347 0.4108713 0.39906874 -0.20761907 2.965294 1.9265318 -0.88537085 0.13650832 0.14457041 0.87329704 0.2897042 2.3216753 -0.7993572 -0.13964903 -0.5425922 -0.62305737 0.78111976 1.9701912 -1.0763782 -0.96336037 0.013077089 -0.556893 0.5211649 1.785957 0.18510284 -0.8814439 -0.6684563 -1.180082 1.7755218 2.6150062 -1.69454 -1.4648407 -0.56289357 -0.16371182 1.9406332 2.1110795 -0.8198425 -0.4969415 1.7835532 0.28608644 -1.196144 -0.29270127 0.10153975 2.3906333 1.6420307 0.2586755 0.011988206 0.45067728 -0.29624397 1.6044993 0.78145796 -0.011525693 0.33456394 1.7233483 -0.5218978 2.1789744 2.9442863 -0.9673672 -0.5366159 1.2356586 -0.99814165 -1.3330446 -0.7047632 0.5930675 -0.21607426 -0.4016614 0.4765675 0.33513865 0.5863817 -1.4150733 -1.1457552 -1.0784752 -1.4136074 1.2577616 2.2369676 -0.7993741 -0.57735014 0.41724074 -1.1991314 -1.2356343 -0.35954204 -1.9902359 -1.1923834 -1.2669723 -0.74948406 -0.944608 -0.022206271 -0.2005942 -0.6672859 -0.15860078 -1.164995 1.5117489 2.2875252 -0.7794424 -1.2357175 -1.3957139 -0.6299822 -1.0302528 -0.47014156 -0.94897807 0.3027232 1.1699802 -1.6886129 -1.4172962 -0.23314042 -1.3050662 -1.3105575 -0.250414 -1.0406073 1.0530531 1.3861068 -0.98728997 -0.8111395 -0.5250111 -1.3926756 -1.3789666 -0.8864904 -0.9631965 -0.45999292 -0.3731309 -1.5666629 1.7220405 1.9361324 -1.3928436 -0.6913503 -1.1877276 -1.1572889 1.0769932 1.5326065 -1.1392767 -0.6570662 -1.3754126 -0.61353916 -0.5842144 -1.4323113 -0.41837806 0.69298 -1.0576129 -0.2920628 0.7907849 1.5956535 -1.1451101 -1.2037153 -0.6246314 -1.3049201 -1.4414631 -1.7579721 -0.9005643 -0.11113467 -0.2844963 -0.47717452 -0.36505267 -0.8792839 -1.9516883 -0.8031113 0.25574464 -0.5890413 -0.12606828 0.2731264 -0.6708617 -0.5554926 -0.6170423 -1.4590741 -0.8039056 -0.6526703 0.07568342 -0.6807577 0.78536797 -0.60310316 -0.4242882 -0.38551784 -0.9125275 0.61118865 -0.028014723 0.9272585 0.439309 2.0132115 -0.6812347 1.255344 1.2869604 -0.6415692 -1.17868 0.83626616 -1.0502765 -0.7674825 0.01511037 -1.3710603 -1.1803217 -0.17523833 -1.2904886 0.40265262 0.58692086 -0.50728464 -0.20899612 0.47045234 -0.6123187 1.220629 1.3916627 -1.8133098 -1.6047415 -1.5027094 -0.10834587 -0.62878513 2.0995924 0.18022265 0.16527613 -0.26341686 0.11748232 1.8073972 1.9291996 -0.17921448 -0.112309925 -0.15622121 0.18022265 0.16527613 -0.26341686 0.11748232 1.8073972 1.9291996 -0.17921448 -0.112309925 -0.15622121 HGA-glucuronide 1.8749039 -0.010741855 -2.5747595 1.5340134 1.4945592 -0.2122038 1.4432993 1.3268226 1.5470327 1.896982 -3.655856 1.6049803 1.6228529 -0.42789984 -3.3351114 1.7568312 1.5376852 2.279554 1.8907217 1.7932562 2.4966013 1.7066629 -3.7672632 -3.771344 1.8181522 -3.03589 -3.2678518 1.8982928 2.1366959 2.8868039 1.6933163 0.54726 -3.141006 1.7564622 1.8624805 1.8208898 1.3258803 1.4174627 2.133647 0.6906674 0.5754084 1.779483 2.1102448 -3.3189409 -2.8455782 2.5033314 -3.3887227 -2.548356 1.8731865 -2.5747595 -3.03589 1.9403251 1.5087919 2.8527594 1.9580866 -2.810608 -2.9691513 1.4947661 1.8006955 2.3928742 1.9624211 1.6495879 2.121925 1.9236501 -0.21770598 -3.1190789 1.1812146 0.96924293 1.6743903 1.8239865 -3.7379537 -3.1622143 1.299348 0.4613247 -3.2123783 1.5631751 -3.7027454 -3.53305 1.7161742 -3.6936355 -2.548356 1.3423693 1.0697868 1.4137067 2.0427508 1.1915805 1.7231596 1.7122065 -3.2678518 -2.7736382 1.19331 -3.1927772 -3.3023553 1.400508 -3.5561523 -3.5504537 1.9898952 1.9311259 1.7676743 1.5792669 -3.202652 -3.2766516 1.2012573 1.3285927 1.7935785 1.413787 -3.5447044 -3.3738532 1.1522516 1.3340919 1.5624739 1.6303219 -3.6655097 -3.3189409 1.5782155 1.7530216 1.827649 1.8889003 -3.5447044 -3.3813305 1.6131663 1.5509431 1.6860338 1.3237818 -3.5029612 -3.509092 1.4641302 1.2513243 1.4572239 1.562939 -3.5029612 -2.9255307 1.3401225 1.4298023 1.2722697 1.9954427 1.3155864 2.1231215 1.5277591 -3.655856 -3.583916 1.8735029 1.4456042 2.045241 1.7102646 -3.6259985 -3.2407095 1.7053632 1.7919619 1.9724648 1.6088215 -3.3508875 -3.0484495 1.4925163 0.9590804 1.6660256 1.4830977 1.2512876 1.1864628 2.038883 1.4349052 1.5507588 1.8554361 -3.7027454 -3.53305 0.6245369 0.9856798 0.8281481 0.8490773 -3.47784 -3.0230818 0.5727131 -3.837045 -3.7027454 1.2924498 1.1789173 1.7647618 1.3928181 1.459811 1.6834339 1.2747371 -3.5151653 -3.2407095 1.7221522 -3.7027454 1.3335865 1.4823337 -3.6208856 -3.6000195 1.5036502 1.7211047 1.423339 1.5491098 1.5868299 1.9742122 0.57823026 -3.6052995 -3.7631567 0.75210685 0.78600717 0.97850156 1.0889887 1.1541791 1.4018754 1.2425257 -3.6982064 -3.5784576 1.0371097 1.1042545 1.5432796 1.0195357 1.4391892 1.5414724 1.3059961 -3.445001 -3.2123783 1.1383716 -0.5729179 -3.5504537 0.8080668 0.8590217 1.1903788 1.342182 -3.5893285 -3.6157317 0.958746 0.946096 0.891804 0.89599484 1.098964 1.0633812 1.1382099 -0.70111513 0.33260843 1.4160573 -3.521182 -3.3586338 1.2251872 1.3214705 1.9461348 1.2079948 0.9636924 0.8271938 1.5281721 -3.7464643 -4.066636 1.5828651 1.4818928 1.3608361 1.0180733 1.472184 2.309032 1.4084272 -3.3738532 -2.8455782 1.4216993 1.3873433 1.558277 0.96810603 1.1466224 1.5252395 1.5273136 1.7584246 2.6082904 1.0304921 -3.396031 -3.3813305 1.3494325 -0.44050884 -3.7293296 1.381496 -3.6105366 -2.520829 1.6479038 -3.594696 -3.3508875 1.403754 0.05229493 0.11963632 1.3982043 1.645132 2.2745864 1.3131486 1.4624169 2.148289 1.2983223 -3.5561523 -3.182749 1.5500175 -0.33042663 -3.53305 0.7846099 -3.396031 -3.2407095 0.93496895 0.95006245 1.2244273 1.2957493 -3.79921 -3.5784576 1.9389912 1.5044172 1.5813931 1.673037 -3.3430476 -2.8787544 1.6921508 1.313931 1.469599 1.9389912 1.5044172 1.5813931 1.673037 -3.3430476 -2.8787544 1.6921508 1.313931 1.469599 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name retention time neutral mass formula CAS-ID KEGG-ID Phenylalanine 3.700001 165.0795 C9 H11 N O2 63-91-2 C00079 Phenylalanine hydrate 2.1599956 183.0869 C9 H13 N O3 Phenylpyruvic acid 4.729989 164.0472 C9 H8 O3 156-06-9 C00166 Phenylacetamide 4.849985 135.0685 C8 H9 N O 103-81-1 C02505 Phenylacetylglutamine 5.5200124 264.1114 C13 H16 N2 O4 28047-15-6 C04148 Tyrosine-glucuronide 3.9200032 357.1009 C15 H19 N O9 Tyramine 2.3599906 137.0841 C8 H11 N O 51-67-2 C00483 HPPA-hydrate 3.6199958 198.0528 C9 H10 O5 HGA-glucuronide 2.4600058 344.0737 C14 H16 O10 METABOLITES_END #END