Integrative proteogenomics using ProteomeGenerator2 Journal Article


Authors: Kwok, N.; Aretz, Z.; Takao, S.; Ser, Z.; Cifani, P.; Kentsis, A.
Article Title: Integrative proteogenomics using ProteomeGenerator2
Abstract: Recent advances in nucleic acid sequencing now permit rapid and genome-scale analysis of genetic variation and transcription, enabling population-scale studies of human biology, disease, and diverse organisms. Likewise, advances in mass spectrometry proteomics now permit highly sensitive and accurate studies of protein expression at the whole proteome-scale. However, most proteomic studies rely on consensus databases to match spectra to peptide and protein sequences, and thus remain limited to the analysis of canonical protein sequences. Here, we develop ProteomeGenerator2 (PG2), based on the scalable and modular ProteomeGenerator framework. PG2 integrates genome and transcriptome sequencing to incorporate protein variants containing amino acid substitutions, insertions, and deletions, as well as noncanonical reading frames, exons, and other variants caused by genomic and transcriptomic variation. We benchmarked PG2 using synthetic data and genomic, transcriptomic, and proteomic analysis of human leukemia cells. PG2 can be integrated with current and emerging sequencing technologies, assemblers, variant callers, and mass spectral analysis algorithms, and is available open-source from https://github.com/kentsisresearchgroup/ProteomeGenerator2. © 2023 American Chemical Society.
Keywords: mass spectrometry; peptide; proteomics; transcriptomics; peptides; genomics; procedures; humans; human; proteogenomics; comprehensive proteomics
Journal Title: Journal of Proteome Research
Volume: 22
Issue: 8
ISSN: 1535-3893
Publisher: American Chemical Society  
Date Published: 2023-08-04
Start Page: 2750
End Page: 2764
Language: English
DOI: 10.1021/acs.jproteome.3c00005
PUBMED: 37418425
PROVIDER: scopus
PMCID: PMC10783198
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA0098748) acknowledged in PubMed and PDF -- MSK corresponding author is Alex Kentsis -- Source: Scopus
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MSK Authors
  1. Alex   Kentsis
    104 Kentsis
  2. Paolo   Cifani
    32 Cifani
  3. Sumiko Takao
    9 Takao
  4. Zheng Ser
    5 Ser
  5. Zita Aretz
    6 Aretz
  6. Nathaniel Kwok
    1 Kwok