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Human Prestin: A Candidate PE1 Protein Lacking Stringent Mass Spectrometric Evidence?
- Mohamedali, Abidali, Ahn, Seong Beom, Sreenivasan, Varun K. A., Ranganathan, Shoba, Baker, Mark S.
- Journal of Proteome Research 2017 v.16 no.12 pp. 4531-4535
- antibodies, chromosomes, clearcutting, humans, mass spectrometry, peptides, proteins, proteome, transcriptomics
- The evidence that any protein exists in the Human Proteome Project (HPP; protein evidence 1 or PE1) has revolved primarily (although not exclusively) around mass spectrometry (MS) (93% of PE1 proteins have MS evidence in the latest neXtProt release), with robust and stringent, well-curated metrics that have served the community well. This has led to a significant number of proteins still considered “missing” (i.e., PE2–4). Many PE2–4 proteins have MS evidence of unacceptable quality (small or not enough unitypic peptides and unacceptably high protein/peptide FDRs), transcriptomic, or antibody evidence. Here we use a Chromosome 7 PE2 example called Prestin to demonstrate that clear and robust criteria/metrics need to be developed for proteins that may not or cannot produce clear-cut MS evidence while possessing significant non-MS evidence, including disease-association data. Many of the PE2–4 proteins are inaccessible, spatiotemporally expressed in a limited way, or expressed at such a very low copy number as to be unable to be detected by current MS methodologies. We propose that the HPP community consider and lead a communal initiative to accelerate the discovery and characterization of these types of “missing” proteins.