Michigan Compound Identification Development Cores (MCIDC)

点击翻译按钮获取中文摘要

Overall - Project Summary As a member of the NIH Common Funds Metabolomics Consortium, the Michigan Compound Identification Development Core (MCIDC) will using cutting-edge computational and experimental methods to systematically identify metabolites among the high proportion of features in untargeted metabolomics data which are presently considered unknown. In so doing, we will address a long-standing challenge in the field of metabolomics and enhance biological insights from extant and future metabolomics data. Our data will greatly contribute to platform-agnostic, rapidly-searchable metabolite databases, and the methods we develop will facilitate future compound identification efforts. We will achieve these goals by carrying out the following aims: Through the computational core of MCIDC, we will refine software currently operational in our lab that aids in annotation of features in untargeted metabolomics data as either primary features or as artifacts or degenerate features (e.g., isotopes, fragments, adducts, contaminants). This software will help prioritize identification efforts on primary features, while allowing artifacts and degenerate features to be indexed and rapidly removed from future data sets. We will implement a `hybrid search' approach that will allow unknown metabolite spectra to be searched against both in-silico and experimentally-derived spectra of compounds with similar structural motifs. We expect this approach will improve certainty of metabolite identification compared to in-silico spectra alone. We will contribute our data output to the National Metabolomics Data Repository and other databases. Through the experimental core of MCIDC, we will develop and implement novel and cutting-edge analytical technologies to aid in compound identification, and will systematically apply these techniques to unknown primary features in metabolomics data determined to be of high priority based on survey of public metabolomics databases. Techniques we will use to identify metabolites include high-resolution tandem mass spectrometry (MSn), ion mobility spectrometry, high-resolution chromatographic methods including ultra-high pressure liquid chromatography, sample pre-fractionation and multidimensional separations, in-vivo stable isotope labeling for structural elucidation, chemical derivatization, pre-concentration followed by NMR analysis, and (when necessary) synthesis and characterization of novel metabolite standards. Finally, through our administrative core, we will ensure coordinated operation between our own experimental and computational cores, and with other members of the NIH common funds metabolomics consortium. By coordinating between CIDC sites and prioritizing compound identification tasks as a group, we will maximize productivity and improve outcome of the metabolomics consortium efforts. By carrying out these aims, we anticipate that our CIDC will yield a lasting, unifying impact on interpretation of biological findings from the rich and growing datasets yielded by untargeted metabolomics.