Metabolomics reporting standards proposed Recently published recommendations from the Standard Metabolic Reporting Structure (SMRS) group have moved researchers in the metabonomics/metabolomics community one step closer to consensus standards for designing metabolic experiments and recording their results (Nat. Biotechnol. 2005, 23, 833– 838). But the dialogue at the Metabolomics Standards Workshop, held August 1–2 in Bethesda, Md., suggested that scientists interested in studying metabolic changes in living systems still have work to do before they can shift their focus from evaluating analytical techniques to understanding what the biological measurements mean. “If you read your average scientific paper, it doesn’t give you enough information to adequately interpret a metabonomics experiment,” says Don Robertson, who is with the Metabonomics Evaluation Group at Pfizer and is an author of the SMRS paper. “The whole point of standards is to provide people with the information they need to interpret your data.” Although the participants in this process are drawing on the experiences of other “—omics” collaborations, experts say that the complexity of metabolomics information raises new issues. Like proteomics, metabolomics will require data structures that can account for multiple analytical platforms and preparation procedures. “We originally envisaged a MIAME [minimum information about a microarray experiment] type [of] structure, as [is] used for gene expression data, but very quickly discovered that this was far too simplistic for metabolic data,” says Jeremy K. Nicholson, who is at Imperial College London and is an author of the SMRS paper. The SMRS standards summarize the consensus coming out of the group’s second meeting, held April 5–6, 2004, in Lausanne (Switzerland). As such, they are meant to be descriptive, rather than prescriptive, and to provide a solid basis for further discussions, says the paper’s lead author, John C. Lindon of Imperial College London. The standards also are designed to strike a balance between academics’ desire for full data disclosure and the pharmaceutical industry’s need to protect intellectual
property by recommending different reporting standards for public databases, journal supplementary data, and regulatory submissions. The discussions during the Bethesda meeting, which was sponsored by the National Institutes of Health and the Metabolomics Society, led to the creation of a new working group. The group will endeavor to make the SMRS standards globally acceptable. The current SMRS standards propose minimum requirements in three areas: origins of biological samples, analytical technologies and methods, and multivariate statistical methods. For biological materials, researchers should report metadata about their source,
Metabolomics data. An NMR spectrum of rat urine
metabolites.
maintenance, collection, storage, handling, and preparation. Reporting becomes more complex with animal studies, for which factors such as the type of feed and the animal’s level of activity at
the time of sample collection should be recorded. Participants at the recent meeting did not define the level of detail required to make accurate comparisons between studies possible. “Obviously, everyone cannot have the same water supply,” says Robertson. “We have to be flexible enough that people can adopt these standards.” Moving forward, experts say that the standards, which originally focused on NMR and MS, should account for additional analytical platforms, including chromatography, CE, and ion-selective electrodes. Researchers also should record metadata associated with the analysis. Finally, the multivariate statistics or chemometrics used to analyze the biological measurements should be tested and validated. Outliers can be excluded from the analysis in certain cases—for example, if an animal is known to be diseased. But “you have to have criteria for the exclusion of outliers. They cannot just be excluded to improve the statistical model,” explains Lindon. Other working groups will focus on collecting metadata, developing a standard vocabulary, creating file formats to report data, and establishing a metabolite reference database. “Even if we aren’t able to achieve standards as quickly as we’d like, the whole community forming around this synergy is very important,” says Pedro Mendes at Virginia Bioinformatics Institute. —Vida Foubister
Capturing metabolomics data Participants at MetaboMeeting 1.0, held July 18–19 at the University of Cambridge (U.K.), made progress toward the implementation of selected metabolomics standards, including the development of a common NMR data format. The meeting also focused on the potential for synergies between the “— omics” collaborations. For example, the Metabolomics Society might emulate the relationships that both the HUPO Proteomics Standards Initiative (PSI) and the Microarray Gene Expression Data Society have established with instrument and software vendors, funding agencies, governments, and publishers. Researchers also say that the MS data-capture system developed by PSI can be successfully applied to metabolomics data. Further, the PRIDE proteomics database will soon be adapted for metabolomics. The experience gained while developing a common ontology for transcriptomics and proteomics will also guide researchers in the creation of an ontology for metabolic studies. But perhaps the most critical lesson from the other “—omics” initiatives is to avoid conflict. “You don’t want competitive efforts, because the whole purpose of a standard is that we all benefit from each other’s science,” says Chris Taylor at the European Bioinformatics Institute.
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