assessment of metabolome annotation quality a method for evaluating the false discovery rate of elemental composition searches代谢物注释质量的评估方法评估基本的错误发现率组合搜索.pdf

Assessment of Metabolome Annotation Quality: A Method for Evaluating the False Discovery Rate of Elemental Composition Searches 1 2 1 1,3 4 Fumio Matsuda , Yoko Shinbo , Akira Oikawa , Masami Yokota Hirai , Oliver Fiehn , Shigehiko Kanaya1,2,3, Kazuki Saito1,5* 1 Metabolome Research Group, RIKEN Plant Science Center, Yokohama, Kanagawa, Japan, 2 Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan, 3 Japan Science and Technology Agency, CREST, Kawaguchi, Saitama, Japan, 4 Metabolomics Research Laboratory, UC Davis Genome Center, Davis, California, United States of America, 5 Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan Abstract Background: In metabolomics researches using mass spectrometry (MS), systematic searching of high-resolution mass data against compound databases is often the first step of metabolite annotation to determine elemental compositions possessing similar theoretical mass numbers. However, incorrect hits derived from errors in mass analyses will be included in the results of elemental composition searches. To assess the quality of peak annotation information, a novel methodology for false discovery rates (FDR) evaluation is presented in this study. Based on the FDR analyses, several aspects of an elemental composition search, including setting a threshold, estimating FDR, and the types of elemental composition databases most reliable for searching are discussed. Methodology/Principal Findings: The FDR can be determined from one measured value (i.e., the hit rate for search queries) and four parameters determined by Monte Carlo simulation. The resu