RT Journal Article SR Electronic T1 Exposing the Exposome with Global Metabolomics and Cognitive Computing JF bioRxiv FD Cold Spring Harbor Laboratory SP 145722 DO 10.1101/145722 A1 Benedikt Warth A1 Scott Spangler A1 Mingliang Fang A1 Caroline H Johnson A1 Erica M Forsberg A1 Ana Granados A1 Richard L Martin A1 Xavi Domingo A1 Tao Huan A1 Duane Rinehart A1 J Rafael Montenegro-Burke A1 Brian Hilmers A1 Aries Aisporna A1 Linh T Hoang A1 Winnie Uritboonthai A1 Paul Benton A1 Susan D Richardson A1 Antony J Williams A1 Gary Siuzdak YR 2017 UL http://biorxiv.org/content/early/2017/06/08/145722.abstract AB Concurrent exposure to a wide variety of xenobiotics and their combined toxic effects can play a pivotal role in health and disease, yet are largely unexplored. Investigating the totality of these exposures, i.e. the exposome, and their specific biological effects constitutes a new paradigm for environmental health but still lacks high-throughput, user-friendly technology. We demonstrate the utility of mass spectrometry-based global exposure metabolomics combined with tailored database queries and cognitive computing for comprehensive exposure assessment and the straightforward elucidation of biological effects. The METLIN Exposome database has been redesigned to help identify environmental toxicants, food contaminants and supplements, drugs, and antibiotics as well as their biotransformation products, through its expansion with over 700,000 chemical structures to now include more than 950,000 unique small molecules. More importantly, we demonstrate how the XCMS/METLIN platform now allows for the readout of the biological effect of a toxicant through metabolomic-derived pathway analysis and further, cognitive computing provides a means of assessing the role of a potential toxicant. The presented workflow addresses many of the outstanding methodological challenges current exposome research is facing and will serve to gain a deeper understanding of the impact of environmental exposures and combinatory toxic effects on human health.