MetaboAnalyst 3.0—making metabolomics more meaningful

Xia, Jianguo; Sinelnikov, Igor; Han, Byoung-Sung; Wishart, David S.

doi:10.1093/nar/gkv380

Cited by 2,463 publications

(2,019 citation statements)

References 31 publications

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“…Cohen's d – calculated as the mean difference of the paired, within‐subject scores before and after treatment, divided by the standard deviation of the differences – was used as an estimate of effect size. Metabolomic data were log‐transformed, scaled by control standard deviations, and analyzed by multivariate partial least squares discriminant analysis (PLSDA), with pairwise comparisons and post hoc correction for multiple hypothesis testing using Fisher's least significant difference method in MetaboAnalyst,45 or the false discovery rate (FDR) method of Benjamini and Hochberg. Metabolites with variable importance in projection (VIP) scores determined by PLSDA that were greater than 1.5 were considered significant.…”

Section: Methodsmentioning

confidence: 99%

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Naviaux

Curtis

et al. 2017

Ann Clin Transl Neurol

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ObjectiveNo drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low‐dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment‐1 (SAT‐1) trial was a double‐blind, placebo‐controlled, translational pilot study to examine the safety and activity of low‐dose suramin in children with ASD.MethodsTen male subjects with ASD, ages 5–14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS‐2 comparison scores and Expressive One‐Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire.ResultsBlood levels of suramin were 12 ± 1.5 μmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 μmol/L after 6 weeks. The terminal half‐life was 14.7 ± 0.7 days. A self‐limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS‐2 comparison scores improved by −1.6 ± 0.55 points (n = 5; 95% CI = −2.3 to −0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors.InterpretationThe safety and activity of low‐dose suramin showed promise as a novel approach to treatment of ASD in this small study.

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Section: Methodsmentioning

confidence: 99%

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Naviaux

Curtis

et al. 2017

Ann Clin Transl Neurol

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“…A total of 29/212 (13.6%) urinary metabolites with variable importance on projection scores >1 were identified (http://onlinelibrary.wiley.com/doi/10.1002/hep4.1176/full). The up‐regulated metabolites in NRs were linked to the energy metabolism/trichloroacetic acid cycle; D‐glutamine/D‐glutamate metabolism; alanine, aspartate, and glutamate metabolism; lysine biosynthesis; and vitamin B6 metabolism ( P < 0.05; pathway impact >0.05)22 (see http://onlinelibrary.wiley.com/doi/10.1002/hep4.1176/full; Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

“…This normalization method has been introduced into the Metaboanalyst 3.0 (http://www.metaboanalyst.ca) server21, 22 and into SIMCA P12 software (Umetrix, Sweden) for multivariate projection analyses, such as principal component analysis and partial least square discriminant analysis. A three‐step statistical filtering of the metabolites was carried out, as detailed in http://onlinelibrary.wiley.com/doi/10.1002/hep4.1176/full and the http://onlinelibrary.wiley.com/doi/10.1002/hep4.1176/full).…”

Section: Methodsmentioning

confidence: 99%

“…A three‐step statistical filtering of the metabolites was carried out, as detailed in http://onlinelibrary.wiley.com/doi/10.1002/hep4.1176/full and the http://onlinelibrary.wiley.com/doi/10.1002/hep4.1176/full). Pathway enrichment patterns were analyzed using Metaboanalyst,22 a web‐based tool designed for untargeted metabolomics data and pathway analysis.…”

Section: Methodsmentioning

confidence: 99%

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Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Maras

Das

Sharma

et al. 2018

Hepatology Communications

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Severe alcoholic hepatitis (SAH) has a high mortality rate, and corticosteroid therapy is effective in 60% patients. This study aimed to investigate a baseline metabolic phenotype that could help stratify patients not likely to respond to steroid therapy and to have an unfavorable outcome. Baseline urine metabolome was studied in patients with SAH using ultra‐high performance liquid chromatography and high‐resolution mass spectrometry. Patients were categorized as responders (Rs, n = 52) and nonresponders (NRs, n = 8) at day 7 according to the Lille score. Multivariate projection analysis identified metabolites in the discovery cohort (n = 60) and assessed these in a validation cohort of 80 patients (60 Rs, 20 NRs). A total of 212 features were annotated by using metabolomic/biochemical/spectral databases for metabolite identification. After a stringent selection procedure, a total of nine urinary metabolites linked to mitochondrial functions significantly discriminated nonresponders, most importantly by increased acetyl‐L‐carnitine (12‐fold), octanoylcarnitine (4‐fold), decanoylcarnitine (4‐fold), and alpha‐ketoglutaric acid (2‐fold) levels. Additionally, urinary acetyl‐L‐carnitine and 3‐hydroxysebasic acid discriminated nonsurvivors (P < 0.01). These urinary metabolites significantly correlated to severity indices and mortality (r > 0.3; P < 0.01) and were associated with nonresponse (odds ratio >3.0; P < 0.001). In the validation cohort, baseline urinary acetyl‐L‐carnitine documented an area under the receiver operating curve of 0.96 (0.85‐0.99) for nonresponse prediction and a hazard ratio of 3.5 (1.5‐8.3) for the prediction of mortality in patients with SAH. Acetyl‐L‐carnitine at a level of >2,500 ng/mL reliably segregated survivors from nonsurvivors (P < 0.01, log‐rank test) in our study cohort. Conclusion: Urinary metabolome signatures related to mitochondrial functions can predict pretherapy steroid response and disease outcome in patients with SAH. (Hepatology Communications 2018;2:628‐643)

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“…23 All data were normalised to total peak area for each sample. Log 2 transformation was applied for univariate analysis to enhance a normal distribution in the datasets.…”

Section: Statistical Analysis Of Retina Stabilitymentioning

confidence: 99%

Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina

Tan

Mullard

Hollywood

et al. 2016

Experimental Eye Research

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and 48 hours post-mortem. To study the metabolite composition of rat ocular tissues, eyes were dissected immediately after culling to isolate the cornea, lens, vitreous and retina, prior to storing at -80 o C. Tissue extracts were subjected to Gas Chromatograph Mass Spectrometry (GC-MS) and Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS). Generally, the metabolic composition of the retina was stable for 8 hours post-mortem when eyes were stored at 4 o C, but showed increasing changes thereafter. However, some more rapid changes were observed such as increases in TCA cycle metabolites after 2 hours post-mortem, whereas some metabolites such as fatty acids only showed decreases in concentration from 24 hours. A total of 42 metabolites were identified across the ocular tissues by GC-MS (MSI level 1) and 2782 metabolites were annotated by UHPLC-MS (MSI level 2) according to MSI reporting standards. Many of the metabolites detected were common to all of the tissues but some metabolites showed partitioning between different ocular structures with 655, 297, 93 and 13 metabolites being uniquely detected in the retina, lens, cornea and vitreous respectively. Only a small percentage (1.6%) of metabolites found in the vitreous were exclusively found in the retina and not other tissues. In conclusion, mass

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MetaboAnalyst 3.0—making metabolomics more meaningful

Cited by 2,463 publications

References 31 publications

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina

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