NEW YORK – Ten years after its official launch, the Human Proteome Organization's Human Proteome Project (HPP) has reached coverage of 90 percent of all predicted human proteins.
As detailed in a study published this week in Nature Communications (with a pair of additional papers published here and here this week in the Journal of Proteome Research) and highlighted at the annual HUPO meeting, held online this week, project researchers have detected 17,874 of the 19,773 proteins predicted to be encoded by the human genome, an increase of more than 4,000 proteins since the initiative published its first report in 2011.
Of those, 16,924 identifications have been validated by mass spectrometry, with the other 950 corroborated by non-mass spec approaches like immunoassays.
While the project continues to pursue identification of the remaining 10 percent of predicted proteins, the process has become slower and more difficult in recent years as many of the outstanding proteins are either expressed only in very specific and hard-to-obtain tissue types or are difficult to isolate and analyze using traditional proteomic technologies. For instance, the JPR authors noted that among the 1,899 proteins still undetected, as many as 1,000 have also gone undetected at the transcript level. Olfactory receptors have been a particular sticking point for the project, with no proteins having ever been found for any of 399 known olfactory receptor genes, including in analyses of supra-nasal olfactory epithelium specimens.
As progress towards completing the proteome survey has slowed and the proteomics field has shifted from identifying and cataloguing proteins to exploring their biological function and disease relevance, the HPP is similarly moving towards exploring protein function and developing new research resources, said Robert Moritz, head of proteomics research at the Institute for Systems Biology and chair of the HPP.
He noted that a key goal of the initiative has been to expand the number of proteins researchers investigate in their work by providing information on how to detect them.
"The vast majority of research has been done on a very small class of proteins because they are readily detectable and the reagents are there," he said. "That's what we've been striving to do, to first understand the parts list [of the proteome] and then to create the resources around each of those proteins so they can be worked on, whether it be by mass spectrometry or by Edman degradation or even with new technologies that are coming out."
Moving forward, the HPP has identified a number of focus areas, including extending its efforts to identify the many different forms, or proteoforms, of each human protein and to develop and make available optimized assays for the detection of identified proteins, including low-abundance proteins and other hard-to-detect molecules that may need more tailored approaches.