Putting Humpty Dumpty Back Together Again: What Does Protein Quantification Mean in Bottom-Up Proteomics?

Plubell, Deanna L.; Käll, Lukas; Webb-Robertson, Bobbie-Jo; Bramer, Lisa M.; Ives, Ashley; Kelleher, Neil L.; Smith, Lloyd M.; Montine, Thomas J.; Wu, Christine C.; MacCoss, Michael J.

doi:10.1021/acs.jproteome.1c00894

Title: Putting Humpty Dumpty Back Together Again: What Does Protein Quantification Mean in Bottom-Up Proteomics?

Journal Article · Sun Feb 27 00:00:00 EST 2022 · Journal of Proteome Research

DOI:https://doi.org/10.1021/acs.jproteome.1c00894· OSTI ID:1862287

^[1];

^[2]; Webb-Robertson, Bobbie-Jo ^[3];

^[3];

^[4];

^[4]; Smith, Lloyd M. ^[5];

^[6]; Wu, Christine C. ^[1];

^[1]

Univ. of Washington, Seattle, WA (United States)
KTH Royal Inst. of Technology, Stockholm (Sweden)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Northwestern Univ., Evanston, IL (United States)
Univ. of Wisconsin, Madison, WI (United States)
Stanford Univ., CA (United States)

Bottom-up proteomics provides peptide measurements and has been invaluable for moving proteomics into large-scale analyses. Commonly, a single quantitative value is reported for each protein-coding gene by aggregating peptide quantities into protein groups following protein inference or parsimony. However, given the complexity of both RNA splicing and post-translational protein modification, it is overly simplistic to assume that all peptides that map to a singular protein-coding gene will demonstrate the same quantitative response. Here, by assuming that all peptides from a protein-coding sequence are representative of the same protein, we may miss the discovery of important biological differences. To capture the contributions of existing proteoforms, we need to reconsider the practice of aggregating protein values to a single quantity per protein-coding gene.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Univ. of Washington, Seattle, WA (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); Swedish Research Council (SRC); National Institute of Health

Grant/Contract Number:: AC05-76RL01830; U19AG065156; RF1AG053959; P41GM103533; F31AG069420; P41GM108569; UH3CA246635; R35GM126914; 2017-04030; U01-1CA184783; AC06-76RL01830

OSTI ID:: 1862287

Alternate ID(s):: OSTI ID: 1860630

Report Number(s):: PNNL-SA-159627

Journal Information:: Journal of Proteome Research, Vol. 21, Issue 4; ISSN 1535-3893

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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