CELL SIGNALING TECHNOLOGY, INC.

The parent grant supports the development of PhosphoSitePlus© (PSP) a cutting-edge web-based biomedical research used weekly by thousands of researchers around the world. PSP aggregates information about protein post-translational modifications (PTMs). PTMs are chemical groups that are enzymatically added or removed from specific locations on proteins, and are fundamental components of almost all aspects of cellular communication. PSP provides unique and powerful tools for biomedical researchers that will accelerate the pace of discovery of basic mechanisms of cellular signaling, further our understanding of cellular regulation in health and disease, and facilitate the discovery of important disease markers and therapeutic targets. Notably, PSP integrates all sources of data, from both low- and high-throughput (LTP and HTP) sources, into a single reliable and comprehensive resource. LTP data has been manually curated from nearly 10,000 seminal journal articles by expert scientists at CST over the past eight years. HTP data has been curated by bioinformatics scientists at CST both from published literature and from previously unpublished data from CST. CST is in a unique position to make seminal contributions to PSP: we have been at the forefront of the technological revolution in phosphoproteomics. For example, over the past seven years, CST scientists have discovered tens of thousands of phospho-tyrosine sites from hundreds of different cancer samples. Some of these sites have been published in the literature, but because of the length of time that it can take to get results published (6 – 18 months), we have chosen to make many newly discovered sites available via PSP prior to external publication. PSP has become a leading resource for the aggregation and dissemination of protein modification data throughout the world. The data in PSP is shared in multiple ways: 1) Thousands of protein and modification site pages are viewed by hundreds of users each day. The majority of users are from universities and not-for-profit research institutions; 2) Targeted datasets are downloaded from various PSP web pages hundreds of times per month; 3) inclusive datasets are provided regularly to scores of university and bioinformatics centers including the Swiss Institute of Bioinformatics (UniPROT), the Weizmann Institute (GeneCards), the European Bioinformatics Institute in Hinxton, the Institute for Systems Biology in Seattle, labs at MIT, Harvard, Columbia, Brown, Johns Hopkins Medial Institutions, Yale, UCSF, University of Colorado, University of Toronto, Pompeu Fabra University (Barcelona), etc.; and 4) via links from many outside resources including Nature Signaling Gateway (pending), UniPROT KB (Geneva), GeneCards (Rehovot), multiple University bioinformatics labs, etc. PSP is an unqualified success and has become the leader in the area of protein modification bioinformatics. However, we have to increase our curatorial staff in order to ‘catch-up’ with the enormous amount of recently published data. ARRA funds will allow us to process and curate new modification sites published in journals through 2010, and provide seed money new hires. A delay in constructing a new semi automated ‘pipeline’ for processing HTP data, along with rising flood of phosphorylation data, have outstripped our limited curatorial resources. We find ourselves 4-6 months behind curating published HTP literature. These funds will 1) support a new bioinformatics curator who will assist in the curation of data from HTP literature. Our new HTP processing ‘pipeline’ will increase the efficiency and throughput of this bioinformatics curator. 2) allow us to continue the employment of a scientist who curates data from the LTP literature; and 3) partially support a programmer, allowing our team to export data from PSP into pathway visualization software that will enable researchers in other labs to visualize the rich data in PSP.

Clarification of Codes