HMDB: the Human Metabolome Database

The Human Metabolome Database (HMDB) is currently the most complete and comprehensive curated collection of human metabolite and human metabolism data in the world. It contains records for more than 2180 endogenous metabolites with information gathered from thousands of books, journal articles and electronic databases. In addition to its comprehensive literature-derived data, the HMDB also contains an extensive collection of experimental metabolite concentration data compiled from hundreds of mass spectra (MS) and Nuclear Magnetic resonance (NMR) metabolomic analyses performed on urine, blood and cerebrospinal fluid samples. This is further supplemented with thousands of NMR and MS spectra collected on purified, reference metabolites. Each metabolite entry in the HMDB contains an average of 90 separate data fields including a comprehensive compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, biofluid concentrations, disease associations, pathway information, enzyme data, gene sequence data, SNP and mutation data as well as extensive links to images, references and other public databases. Extensive searching, relational querying and data browsing tools are also provided. The HMDB is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. The HMDB is available at

The Human Serum Metabolome

Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca

Abstracts from the NIHR INVOLVE Conference 2017

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Y-chromosomal DNA analyzed for four prehistoric cemeteries from Cis-Baikal, Siberia

International audienceThe Lake Baikal region of Siberia was home to two temporally distinct populations from Early Neolithic, EN(7500–7000 cal BP) to Late Neolithic-Early Bronze Age, LN-EBA (5570–3725 cal BP). The EN group was separatedfromthe LN-EBA group by a ~1500-year gap (hiatus), and during this hiatus no human remains have been recoveredfrom the Lake Baikal area. Examination of the paternal lineage through Y-chromosomal polymorphisms is anovel approach to BAP andwill facilitate the assessment of the paternal continuities and/or discontinuitieswithinand between the EN and the LN-EBA groups, and complement the previously examined maternal data. Severalnew ancient DNA extraction and PCR amplification techniques were optimized to address the technical challengesduring sample analysis. Each sample was extracted twice in duplicate on different occasions to authenticatethe results. Thirteen Y-chromosomal Single Nucleotide Polymorphism(SNP)markerswere examined via theSNaPshot multiplex PCR reaction to determine Y-chromosomal haplogroups of males. Results have been obtainedfrom16 males fromthe EN cemeteries Lokomotiv and Shamanka II representing haplogroups K, R1a1 and C3,and 20males from the LN-EBA Ust'-Ida and Kurma XI cemeteries representing haplogroups Q, K and unidentifiedSNP (L914). For those males belonging to haplogroup Q, further experiments were obtained to examine subhaplogroupsof Q, and the results showed that thosemales belong to sub-haplogroup Q1a3. The paternal Y-chromosomeresults suggest a discontinuity between the EN and LN-EBA populations. The significance of this researchlies on the utility of DNA analysis in making inferences about the pre-historic social structure

Mitochondriome and cholangiocellular carcinoma.

Cholangiocellular carcinoma (CCA) of the liver was the target of more interest, recently, due mainly to its increased incidence and possible association to new environmental factors. Somatic mitochondrial DNA (mtDNA) mutations have been found in several cancers. Some of these malignancies contain changes of mtDNA, which are not or, very rarely, found in the mtDNA databases. In terms of evolutionary genetics and oncology, these data are extremely interesting and may be considered a sign of poor fitness, which may conduct in some way to different cellular processes, including carcinogenesis. MitoChip analysis is a strong tool for investigations in experimental oncology and was carried out on three CCA cell lines (HuCCT1, Huh-28 and OZ) with different outcome in human and a Papova-immortalized normal hepatocyte cell line (THLE-3). Real time quantitative PCR, western blot analysis, transmission electron microscopy, confocal laser microscopy, and metabolic assays including L-Lactate and NAD+/NADH assays were meticulously used to identify mtDNA copy number, oxidative phosphorylation (OXPHOS) content, ultrastructural morphology, mitochondrial membrane potential (ΔΨm), and differential composition of metabolites, respectively. Among 102 mtDNA changes observed in the CCA cell lines, 28 were non-synonymous coding region alterations resulting in an amino acid change. Thirty-eight were synonymous and 30 involved ribosomal RNA (rRNA) and transfer RNA (tRNA) regions. We found three new heteroplasmic mutations in two CCA cell lines (HuCCT1 and Huh-28). Interestingly, mtDNA copy number was decreased in all three CCA cell lines, while complexes I and III were decreased with depolarization of mitochondria. L-Lactate and NAD+/NADH assays were increased in all three CCA cell lines. MtDNA alterations seem to be a common event in CCA. This is the first study using MitoChip analysis with comprehensive metabolic studies in CCA cell lines potentially creating a platform for future studies on the interactions between normal and neoplastic cells

Maternal Exposure to Bisphenol-A and Fetal Growth Restriction: A Case-Referent Study

We conducted a case-referent study of the effect of exposure to bisphenol-A on fetal growth in utero in full-term, live-born singletons in Alberta, Canada. Newborns <10 percentile of expected weight for gestational age and sex were individually matched on sex, maternal smoking and maternal age to referents with weight appropriate to gestational age. Exposure of the fetus to bisphenol-A was estimated from maternal serum collected at 15–16 weeks of gestation. We pooled sera across subjects for exposure assessment, stratified on case-referent status and sex. Individual 1:1 matching was maintained in assembling 69 case and 69 referent pools created from 550 case-referent pairs. Matched pools had an equal number of aliquots from individual women. We used an analytical strategy conditioning on matched set and total pool-level values of covariates to estimate individual-level effects. Pools of cases and referents had identical geometric mean bisphenol-A concentrations (0.5 ng/mL) and similar geometric standard deviations (2.3–2.5). Mean difference in concentration between matched pools was 0 ng/mL, standard deviation: 1 ng/mL. Stratification by sex and control for confounding did not suggest bisphenol-A increased fetal growth restriction. Our analysis does not provide evidence to support the hypothesis that bisphenol-A contributes to fetal growth restriction in full-term singletons

MitoChip Analysis for HCC and Immortalized Hepatocyte Cell Lines.

<p>Of the 66 mutations observed in the two cell lines (HEPG-2, HuH-7), 18 were non-synonymous coding region mutations (i.e., resulting in an amino acid change), 28 synonymous and 20 involved in non-coding including ribosomal and transfer RNA. Of the 51 alterations observed in Papova-immortalized normal hepatocyte cell line (THLE-3), 10 were non-synonymous coding region alterations, 23 were synonymous and 17 alterations were involved in non-coding, including ribosomal and transfer RNA and one was novel alteration.</p

mtDNA alterations in Cholangiocellular Carcinoma (CCA) and Hepatocellular Carcinoma (HCC) Cell Lines.

<p>Note: RCRS, Revised Cambridge Reference Sequence; both RCRS position and reference nucleotide at that specific position are designed as above. In particular, the highly specific MitoAnalyzer tool (<a href="http://www.cstl.nist.gov/biotech/strbase/mitoanalyzer-direction.html" target="_blank">http://www.cstl.nist.gov/biotech/strbase/mitoanalyzer-direction.html</a>) was used for determining the effect of base substitution on translated protein sequence. The bold base positions are recurrent alterations present in all CCA and HCC cell lines and hepatocyte cell line.</p