FLASHQuant: A Fast Algorithm for Proteoform Quantification in Top-Down Proteomics.

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, American Chemical Society.
    • Subject Terms:
      Proteomics*/methods ; Algorithms*; Chromatography, Liquid/methods ; Software ; Humans ; Proteome/analysis ; Mass Spectrometry/methods ; Tandem Mass Spectrometry/methods
    • Abstract:
      Accurate quantification of individual proteoforms is a crucial step in identifying proteome-wide alterations in different biological conditions. Intact proteoforms have been analyzed predominantly by liquid chromatography-mass spectrometry (LC-MS)-based top-down proteomics (TDP) and quantified primarily by the label-free quantification (LFQ) method, as it requires no additional costly labeling. In TDP, due to frequent coelution and complex signal structures, overlapping signals deriving from multiple proteoforms complicate accurate quantification. Here, we introduce FLASHQuant for MS1-level LFQ analysis in TDP, which is capable of automatically resolving and quantifying coeluting proteoforms. In benchmark tests performed with both spike-in proteins and proteome-level mixture data sets, FLASHQuant was shown to perform highly accurate and reproducible quantification in short runtimes of just a few minutes per LC-MS run. In particular, it was demonstrated that resolving overlapping proteoforms boosts the quantification accuracy. FLASHQuant is publicly available as platform-independent open-source software at https://openms.org/flashquant/, accompanied by the simple alignment algorithm ConsensusFeatureGroupDetector for multiple LC-MS runs.
    • References:
      Nat Biotechnol. 2014 Mar;32(3):219-23. (PMID: 24727770)
      Proteomics. 2014 May;14(10):1195-210. (PMID: 24723472)
      J Proteome Res. 2022 Feb 4;21(2):547-556. (PMID: 34968056)
      J Proteome Res. 2021 Feb 5;20(2):1424-1433. (PMID: 33395532)
      Expert Rev Proteomics. 2020 Oct;17(10):719-733. (PMID: 33232185)
      Sci Adv. 2022 Dec 21;8(51):eabq6348. (PMID: 36542699)
      J Chromatogr A. 2001 Apr 27;915(1-2):1-13. (PMID: 11358238)
      Circ Res. 2019 Nov 8;125(11):936-953. (PMID: 31573406)
      J Am Soc Mass Spectrom. 2021 Jun 2;32(6):1336-1344. (PMID: 33725447)
      Anal Chem. 2020 Apr 7;92(7):4980-4989. (PMID: 32167278)
      Nat Commun. 2022 Jul 29;13(1):4407. (PMID: 35906205)
      J Am Soc Mass Spectrom. 2000 Apr;11(4):320-32. (PMID: 10757168)
      Mol Cell Proteomics. 2014 Jan;13(1):348-59. (PMID: 24176773)
      J Proteome Res. 2011 Sep 2;10(9):4054-65. (PMID: 21751783)
      Anal Chem. 2023 May 30;95(21):8189-8196. (PMID: 37196155)
      J Am Soc Mass Spectrom. 2021 Jun 2;32(6):1278-1294. (PMID: 33983025)
      Mol Omics. 2020 Apr 1;16(2):91-99. (PMID: 31932818)
      Proteomics. 2019 May;19(10):e1800361. (PMID: 31050378)
      J Proteome Res. 2018 Oct 5;17(10):3526-3536. (PMID: 30180576)
      J Am Soc Mass Spectrom. 2019 Aug;30(8):1435-1445. (PMID: 30972727)
      Cell Syst. 2020 Feb 26;10(2):213-218.e6. (PMID: 32078799)
      Anal Chem. 2020 May 19;92(10):7087-7095. (PMID: 32374172)
      Proc Natl Acad Sci U S A. 2020 Oct 6;117(40):24691-24700. (PMID: 32968017)
      Angew Chem Int Ed Engl. 2023 Jul 10;62(28):e202301969. (PMID: 37066813)
      Proteomics. 2014 May;14(10):1211-22. (PMID: 24591407)
      Bioinformatics. 2016 Nov 15;32(22):3495-3497. (PMID: 27423895)
      Anal Chem. 2023 Jun 13;95(23):9090-9096. (PMID: 37252723)
      Nat Methods. 2017 Sep;14(9):909-914. (PMID: 28783154)
      Anal Chem. 2014 Mar 4;86(5):2314-9. (PMID: 24475910)
      Nat Methods. 2024 Mar;21(3):365-367. (PMID: 38366242)
      J Proteome Res. 2021 Sep 3;20(9):4495-4506. (PMID: 34338531)
      J Am Soc Mass Spectrom. 2010 Jun;21(6):879-89. (PMID: 20199872)
      Anal Chem. 2014 May 20;86(10):4961-8. (PMID: 24807621)
      Mass Spectrom Rev. 2023 Mar;42(2):457-495. (PMID: 34047392)
      Nat Methods. 2013 Mar;10(3):186-7. (PMID: 23443629)
      Science. 2022 Jan 28;375(6579):411-418. (PMID: 35084980)
      Proteomics. 2013 Apr;13(7):1053-8. (PMID: 23303686)
      J Am Soc Mass Spectrom. 2007 Nov;18(11):2058-64. (PMID: 17920290)
    • Accession Number:
      0 (Proteome)
    • Publication Date:
      Date Created: 20241018 Date Completed: 20241029 Latest Revision: 20241102
    • Publication Date:
      20241102
    • Accession Number:
      PMC11525931
    • Accession Number:
      10.1021/acs.analchem.4c03117
    • Accession Number:
      39424290