UC2 search: using unique connectivity of uncharged compounds for metabolite annotation by database searching in mass spectrometry-based metabolomics

Abstract

SummaryFor metabolite annotation in metabolomics, variations in the registered states of compounds (charged molecules and multiple components, such as salts) and their redundancy among compound databases could be the cause of misannotations and hamper immediate recognition of the uniqueness of metabolites while searching by mass values measured using mass spectrometry. We developed a search system named UC2 (Unique Connectivity of Uncharged Compounds), where compounds are tentatively neutralized into uncharged states and stored on the basis of their unique connectivity of atoms after removing their stereochemical information using the first block in the hash of the IUPAC International Chemical Identifier, by which false-positive hits are remarkably reduced, both charged and uncharged compounds are properly searched in a single query and records having a unique connectivity are compiled in a single search result.Availability and implementationThe UC2 search tool is available free of charge as a REST web service (http://webs2.kazusa.or.jp/mfsearcher) and a Java-based GUI tool.Supplementary information Supplementary data are available at Bioinformatics online.

“MS-Ready” structures for non-targeted high-resolution mass spectrometry screening studies

“…These results include the neutral form and the substance forms thought to occur in the environment and used in consumer products/commerce, along with associated metadata. Many forms of PFOS may be contained in other public databases, and other strategies have been developed to counteract the anion/neutral form issue during compound searching (e.g., UC2 by Sakurai et al [77]). The current MS-Ready functionality in the Dashboard provides mappings to multiple forms of chemicals related via their “MS-Ready” form in a single search, improving researchers’ ability to identify sources and improve exposure characterization with increased coverage and access to metadata.

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Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry

“…Filtered peaks were then visually checked using MassChroViewer (Sakurai and Shibata 2017) to confirm that the selected peaks were dependent on the administration of maoto (Supplementary Table 1). The metabolite annotation for the detected peaks was performed by searching compound databases or predicting elemental compositions using MFSearcher tool (Sakurai et al 2018) based on the estimated m/z value and adduct ion. UC2 search mode of MFSearcher was applied for database searching with a given mass tolerance of 5 ppm, and the following compound databases were used: KNApSAcK (Afendi et al 2012), KEGG (Kanehisa et al 2019), HMDB (Wishart et al 2018), LIPID MAPS (Fahy et al 2009), and flavonoid database at the web-site https ://metab olomi cs.jp.…”

Metabolome Analysis Identified Okaramines in the Soybean Rhizosphere as a Legacy of Hairy Vetch

“…The detailed parameters for PowerGetBatch are available on our website (http://webs2.kazusa.or.jp/data/ okaramine). The peaks were annotated based on the compound database search using the UC2 database at the MFSearcher website (Sakurai et al, 2018) with the predicted mass values of the original molecules at a given 5-ppm mass tolerance, and the KNApSAcK (Afendi et al, 2012), KEGG (Kanehisa et al, 2016), HMDB (Wishart et al, 2013), LIPID MAPS (Fahy et al, 2009), and flavonoid (http://metabolomics.jp/ wiki/Category : FL) databases. The images of two-dimensional mass chromatograms were generated by MassChroViewer software (Sakurai and Shibata, 2017) using the mzXML files.…”