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J Proteome Res. 2018 Dec 7;17(12):4061-4071. doi: 10.1021/acs.jproteome.8b00442. Epub 2018 Oct 23.

Chromosome 17 Missing Proteins: Recent Progress and Future Directions as Part of the neXt-MP50 Challenge.

Author information

1
Department of Electronic Engineering and Computer Science , University of Michigan , Ann Arbor , Michigan 48109 , United States.
2
Department of Computational Medicine and Bioinformatics , University of Michigan , Ann Arbor , Michigan 48109 , United States.
3
Department of Internal Medicine , University of Michigan , Ann Arbor , Michigan 48109 , United States.
4
Department of Human Genetics and School of Public Health , University of Michigan , Ann Arbor , Michigan 48109 , United States.

Abstract

The Chromosome-centric Human Proteome Project (C-HPP), announced in September 2016, is an initiative to accelerate progress on the detection and characterization of neXtProt PE2,3,4 "missing proteins" (MPs) with a mandate to each chromosome team to find about 50 MPs over 2 years. Here we report major progress toward the neXt-MP50 challenge with 43 newly validated Chr 17 PE1 proteins, of which 25 were based on mass spectrometry, 12 on protein-protein interactions, 3 on a combination of MS and PPI, and 3 with other types of data. Notable among these new PE1 proteins were five keratin-associated proteins, a single olfactory receptor, and five additional membrane-embedded proteins. We evaluate the prospects of finding the remaining 105 MPs coded for on Chr 17, focusing on mass spectrometry and protein-protein interaction approaches. We present a list of 35 prioritized MPs with specific approaches that may be used in further MS and PPI experimental studies. Additionally, we demonstrate how in silico studies can be used to capture individual peptides from major data repositories, documenting one MP that appears to be a strong candidate for PE1. We are close to our goal of finding 50 MPs for Chr 17.

KEYWORDS:

Chromosome-centric Human Proteome Project (C-HPP); Genotype-Tissue Expression (GTEx); Human Protein Atlas; PE1, 2, 3, 4; PeptideAtlas; SRMAtlas; Selective Reaction Monitoring; neXt-MP50 challenge; neXtProt protein existence evidence levels; protein−protein interaction (PPI)

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