ABI Innovation: ProteoCarta: a community-scale resource for multi-species proteomics big data

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Proteomics research focuses on high throughput analysis of proteins, with the ultimate goal of understanding their role in the molecular biology of both simple and complex organisms. Following the successful development of mass spectrometry (MS) technologies, that have enabled the identification and quantification of many thousands of proteins in hundreds of species, the high throughput tandem mass spectrometry approach has become the method of choice for the overwhelming majority of large scale proteomics studies. Data acquisition has proceeding at faster and faster rates, and, combined with the reliability of large scale repositories (e.g., PRIDE, MassIVE, etc) and with journal publication guidelines for quality and annotation, the result has been public availability of hundreds of terabytes of well documented proteomics MS data. The total volume of proteomics data is currently doubling about every 1.5 years. There is tremendous potential for untapped discoveries lying in these 9000+ public datasets. Unfortunately the drive for sharing of raw data has not been accompanied by corresponding efforts to provide protein identification and abundance data, that are required for initial verification by MS experts and subsequent re-use by scientists who are not MS experts. As it stands today, less than 0.1% of all public non-human proteomics MS data only report identifications at the most minimal standards that show acceptable statistical controls; essentially no datasets report quantitative results. The ProteoCarta platform created through this award will address this problem by i) systematically reanalyzing public datasets using advanced computational mass spectrometry workflows and ii) organizing the results in a structured database so that results will be accessible through intuitive query interfaces.Building on computational MS platforms that have already processed over 10 billion spectra in 700,000 jobs from thousands of users in 122 countries, this proposal aims to address this community-scale challenge with a new ProteoCarta resource equipped to systematically reprocess proteomics MS big data from hundreds of species and designed to integrate all results into an open knowledge base that indexes repository-scale global proteomics data. ProteoCarta will significantly scale state of the art algorithms to enable analysis of hundreds of terabytes of data and will extend and integrate new spectral network algorithms for large scale discovery of protein variations within and across samples and species, including MS detection of sequence variants as well as discovery of unexpected or novel post-translational modifications. In addition to releasing all data and analysis results in standard open formats, ProteoCarta results will be directly attached to reanalyzed public datasets, to be stored at MassIVE, whereby hundreds of scientists will be automatically notified of the updates and directly encouraged to actively explore the new results on their own data. Links to resources will be provided through https://cseweb.ucsd.edu/~nbandeir/software.html and https://massive.ucsd.edu/ProteoSAFe/static/massive.jsp .This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.