Project Summary Metabolomics is a rapidly growing -omics technology with vast potential, yet numerous obstacles hinder its full utilization. The development of bioinformatics tools like XCMS Online can streamline the process of analyzing and interpreting raw metabolic data, and further developments like integrating orthogonal data sources and automating metabolite identification are underway. Identifying active metabolites using metabolomics and systems biology strategies is a particularly interesting challenge that will have a significant impact on biomedical research. My overarching goal is not only to address these obstacles, as we have a track record of doing, but also to make our developments freely available and user-friendly and allow the entire community and non-metabolomics experts from all fields (e.g., cancer, neurological disorders, diabetes, virology, environmental exposure, and so on) to harness the enormous opportunity of metabolomics. To this end and based on allocated funding we’ve made multiple aspects of our platform downloadable, for example, METLIN MS2/NL converter, METLIN Avanti MS2 data, METLIN MRM database, METLIN Retention Time database on 80,000 molecular standards, and the just released METLIN Ion Mobility Spectrometry database with 27,000 molecular standards (the largest of its kind), XCMS Online, XCMS-MRM and XCMS. Continued funding will support the development of several interconnected areas of metabolism-related biomedical research that address crucial gaps in metabolomics. These areas include automating metabolomics data analysis, enhancing metabolite annotation and identification, integrating metabolic guidance with system biology data, identifying phenotype-modulating metabolites, and conducting global cooperative quantitative mass spectrometry analysis. Our research team includes multiple junior faculty investigators, including Constantinides and Bollong, who specialize in developing approaches for organ repair regeneration treatment and immunotherapy. For instance, we will focus on identifying potent metabolites that induce oligodendrocyte precursor cells maturation for multiple sclerosis treatment and metabolites that improve the immunological response in a T cell exhaustion model. Our goal is to continue promoting biomedical research by leveraging our cloud-based technologies that currently serve over 50,000 registered users worldwide. Ultimately, we aim to advance biomedical research by developing metabolomic technologies to their full potential. In addition to advancing the technology of measuring and analyzing metabolic data, our prime goal is to correlate these measurements with biological activity. To achieve this, we focus on biomarker discovery, pathway analysis, systems biology data integration, and cognitive computing, which are crucial for identifying metabolites that can actively modulate biological systems and ultimately fix biology with biology. Our efforts in metabolomics development have genera...