Metabolome searcher: a high throughput tool for metabolite identification and metabolic pathway mapping directly from mass spectrometry and using genome restriction

Abstract

BackgroundMass spectrometric analysis of microbial metabolism provides a long list of possible compounds. Restricting the identification of the possible compounds to those produced by the specific organism would benefit the identification process. Currently, identification of mass spectrometry (MS) data is commonly done using empirically derived compound databases. Unfortunately, most databases contain relatively few compounds, leaving long lists of unidentified molecules. Incorporating genome-encoded metabolism enables MS output identification that may not be included in databases. Using an organism’s genome as a database restricts metabolite identification to only those compounds that the organism can produce.ResultsTo address the challenge of metabolomic analysis from MS data, a web-based application to directly search genome-constructed metabolic databases was developed. The user query returns a genome-restricted list of possible compound identifications along with the putative metabolic pathways based on the name, formula, SMILES structure, and the compound mass as defined by the user. Multiple queries can be done simultaneously by submitting a text file created by the user or obtained from the MS analysis software. The user can also provide parameters specific to the experiment’s MS analysis conditions, such as mass deviation, adducts, and detection mode during the query so as to provide additional levels of evidence to produce the tentative identification. The query results are provided as an HTML page and downloadable text file of possible compounds that are restricted to a specific genome. Hyperlinks provided in the HTML file connect the user to the curated metabolic databases housed in ProCyc, a Pathway Tools platform, as well as the KEGG Pathway database for visualization and metabolic pathway analysis.ConclusionsMetabolome Searcher, a web-based tool, facilitates putative compound identification of MS output based on genome-restricted metabolic capability. This enables researchers to rapidly extend the possible identifications of large data sets for metabolites that are not in compound databases. Putative compound names with their associated metabolic pathways from metabolomics data sets are returned to the user for additional biological interpretation and visualization. This novel approach enables compound identification by restricting the possible masses to those encoded in the genome.

Internet Databases of the Properties, Enzymatic Reactions, and Metabolism of Small Molecules—Search Options and Applications in Food Science

“…The replacement of sodium by other cations influenced the kinetics of enzymes involved in 135 bacterial metabolic pathways. Bacterial enzymes and pathways affected by metal cations are described in the ProCyc database (Utah State University, Logan, UT, USA) [36,42]. The results of the cited study are interesting from the point of view of production and consumer acceptance of cheeses with low sodium content.…”

Differentiating signals to make biological sense – A guide through databases for MS‐based non‐targeted metabolomics

“…One relevant possibility is to exclude some compounds from it, an option also present in METLIN. Since most databases were constructed considering utility in human studies , the option to restrict certain types of compound can be particularly useful when using databases for different (model) organisms with a more controlled metabolome . Such options are possible in BioCyc, LipidBank and MassTRIX, where the former two use different data sources based on the restrictions and the latter highlights more plausible hits by organism selection in the output.…”

Updates in metabolomics tools and resources: 2014–2015

“…Metabolite automatic identification toolkit is implemented in R for LC‐MS‐based metabolomics dataset analysis to generate statistical results, peak annotation, and metabolite identification as outputs, with a focus on the peak annotation stage . Metabolome Searcher is a web‐based tool for putative compound identification of MS output based on genome‐restricted metabolic capability, by directly searching genome‐constructed metabolic databases, especially for identifications of large data sets for metabolites that are not in compound databases .…”