TopPICR: A Companion R Package for Top-Down Proteomics Data Analysis

Martin, Evan A.; Fulcher, James M.; Zhou, Mowei; Monroe, Matthew E.; Petyuk, Vladislav A.

doi:10.1021/acs.jproteome.2c00570

Title: TopPICR: A Companion R Package for Top-Down Proteomics Data Analysis

Journal Article · Wed Jan 11 00:00:00 EST 2023 · Journal of Proteome Research

DOI:https://doi.org/10.1021/acs.jproteome.2c00570· OSTI ID:1995421

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Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)

Top-down proteomics is the analysis of proteins in their intact form without proteolysis, thus preserving valuable information about post-translational modifications, isoforms, and proteolytic processing. However, it is still a developing field due to limitations in the instrumentation, difficulties with interpretation of complex mass spectra, and a lack of well-established quantification approaches. TopPIC is one of the popular tools for proteoform identification. Here we extended its capabilities into label-free proteoform quantification by developing a companion R package (TopPICR). Key steps in the TopPICR pipeline include filtering identifications, inferring a minimal set of protein accessions explaining the observed sequences, aligning retention times, recalibrating measured masses, clustering features across datasets, and finally compiling feature intensities using the match-between-runs approach. The output of the pipeline is an MSnSet object which makes downstream data analysis seamlessly compatible with packages from the Bioconductor project. It also provides the capability for visualizing proteoforms within the context of the parent protein sequence. The functionality of TopPICR is demonstrated on top-down LC-MS/MS datasets of 10 human-in-mouse xenografts of luminal and basal breast tumor samples.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: AC05-76RL01830; U01 AG061356

OSTI ID:: 1995421

Report Number(s):: PNNL-SA-177756

Journal Information:: Journal of Proteome Research, Vol. 22, Issue 2; ISSN 1535-3893

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
top-down proteomics
label free quantification
FAIMS
proteoform quantification
TopPIC

Title: TopPICR: A Companion R Package for Top-Down Proteomics Data Analysis

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