Data-Driven Approach To Determine Popular Proteins for Targeted Proteomics Translation of Six Organ Systems

Abstract

Amidst the proteomes of human tissues lie subsets of proteins that are closely involved in conserved pathophysiological processes. Much of biomedical research concerns interrogating disease signature proteins and defining their roles in disease mechanisms. With advances in proteomics technologies, it is now feasible to develop targeted proteomics assays that can accurately quantify protein abundance as well as their post-translational modifications; however, with rapidly accumulating number of studies implicating proteins in diseases, current resources are insufficient to target every protein without judiciously prioritizing the proteins with high significance and impact for assay development. We describe here a data science method to prioritize and expedite assay development on highimpact proteins across research fields by leveraging the biomedical literature record to rank and normalize proteins that are popularly and preferentially published by biomedical researchers. We demonstrate this method by finding priority proteins across six major physiological systems (cardiovascular, cerebral, hepatic, renal, pulmonary, and intestinal). The described method is data-driven and builds upon the collective knowledge of previous publications referenced on PubMed to lend objectivity to target selection. The method and resulting popular protein lists may also be useful for exploring biological processes associated with various physiological systems and research topics, in addition to benefiting ongoing efforts to facilitate the broad translation of proteomics technologies.

Toward Completion of the Human Proteome Parts List: Progress Uncovering Proteins That Are Missing or Have Unknown Function and Developing Analytical Methods

“…38,39 These are proteins that have been studied extensively and reported frequently, for which multiplex-targeted proteomics could provide a potent approach to quantitation and biological insights. Advances in DIA, such as MS-SWATH, could accelerate progress.…”

Highlights of the Biology and Disease-driven Human Proteome Project, 2015–2016

“…Finally, a cross-B/D activity has been the analysis with bibliometric searches of the literature to produce sets of “popular proteins” (highly published) for six organ systems: cardiovascular, cerebral, hepatic, renal, pulmonary, and intestinal. 9 For each protein in each protein set, SRM assays are specified, so that many users can plan appropriate studies. 9 …”

“…9 For each protein in each protein set, SRM assays are specified, so that many users can plan appropriate studies. 9 …”

“…A challenge for MS-based assay method developers is how to strategize development to prioritize important and popular proteins that can contribute to overcoming a bottleneck in technology dissemination. The next step is to broaden this work into other cell and organ types that comprise or influence the cardiovascular systems in health and disease, as reported more recently by Lam et al 9 …”

Advances of the HUPO Human Proteome Project with broad applications for life sciences research

“…The initial approach was to have the proteomics specialists post in the HPP website lists of ‘priority proteins’ for diabetes, aortic disease, and breast, ovarian, and colon cancers amenable to quantitation with proteomics. The latest approach is bibliometric, capturing evidence for the top-50 proteins published by researchers on various organ systems, beginning with cardiovascular, cerebral, hepatic, intestinal, pulmonary, and renal systems [4]. SRM methods are directly applicable for sensitive and quantitative analysis of these ‘popular proteins’ well known to researchers of these organ systems; the approach can readily be expanded to other disease categories for studies of normal biology and physiology and pathological processes.…”