We collected personal, dense, dynamic data for 108 individuals over 9 months, including whole genome sequence; clinical tests, metabolomes, proteomes and microbiomes at three time points; and daily activity tracking. Using these data we generated a correlation network and identified communities of related analytes that were associated with physiology and disease. We demonstrate how connectivity within these communities identified known and candidate biomarkers, e.g. gamma-glutamyltyrosine was densely interconnected with clinical analytes for cardiometabolic disease. We calculated polygenic scores from GWAS for 127 traits and diseases, and identified molecular correlates of polygenic risk, e.g. genetic risk for inflammatory bowel disease was negatively correlated with plasma cystine. Finally, behavioral coaching informed by personalized data helped participants improve clinical biomarkers. Personal, dense, dynamic data clouds will improve understanding of health and disease, especially for early transition states. This approach to “scientific wellness” represents an opportunity largely missing in contemporary health care.
Complete reference maps or datasets, like the genomic map of an organism, are highly beneficial tools for biological and biomedical research. Attempts to generate such reference datasets for a proteome so far failed to reach complete proteome coverage, with saturation apparent at approximately two thirds of the proteomes tested, even for the most thoroughly characterized proteomes. Here, we used a strategy based on high-throughput peptide synthesis and mass spectrometry to generate a close to complete reference map (97% of the genome-predicted proteins) of the S. cerevisiae proteome. We generated two versions of this mass spectrometric map one supporting discovery- (shotgun) and the other hypothesis-driven (targeted) proteomic measurements. The two versions of the map, therefore, constitute a complete set of proteomic assays to support most studies performed with contemporary proteomic technologies. The reference libraries can be browsed via a web-based repository and associated navigation tools. To demonstrate the utility of the reference libraries we applied them to a protein quantitative trait locus (pQTL) analysis, which requires measurement of the same peptides over a large number of samples with high precision. Protein measurements over a set of 78 S. cerevisiae strains revealed a complex relationship between independent genetic loci, impacting on the levels of related proteins. Our results suggest that selective pressure favors the acquisition of sets of polymorphisms that maintain the stoichiometry of protein complexes and pathways.
The ProteomeTools project builds molecular and digital tools from the human proteome to facilitate biomedical and life science research. Here, we report the generation and multimodal LC-MS/MS analysis of >330,000 synthetic tryptic peptides representing essentially all canonical human gene products and exemplify the utility of this data. The resource will be extended to >1 million peptides and all data will be shared with the community via ProteomicsDB and proteomeXchange.
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