AI-Assisted Processing Pipeline to Boost Protein Isoform Detection.

Journal: Methods in molecular biology (Clifton, N.J.)
PMID:

Abstract

Proteomics, the study of proteins within biological systems, has seen remarkable advancements in recent years, with protein isoform detection emerging as one of the next major frontiers. One of the primary challenges is achieving the necessary peptide and protein coverage to confidently differentiate isoforms as a result of the protein inference problem and protein false discovery rate estimation challenge in large data. In this chapter, we describe the application of artificial intelligence-assisted peptide property prediction for database search engine rescoring by Oktoberfest, an approach that has proven effective, particularly for complex samples and extensive search spaces, which can greatly increase peptide coverage. Further, it illustrates a method for increasing isoform coverage by the PickedGroupFDR approach that is designed to excel when applied on large data. Real-world examples are provided to illustrate the utility of the tools in the context of rescoring, protein grouping, and false discovery rate estimation. By implementing these cutting-edge techniques, researchers can achieve a substantial increase in both peptide and isoform coverage, thus unlocking the potential of protein isoform detection in their studies and shedding light on their roles and functions in biological processes.

Authors

  • Matthew The
    Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany.
  • Mario Picciani
    Computational Mass Spectrometry, TUM School of Life Sciences, Technical University of Munich, Freising, Germany.
  • Cecilia Jensen
    Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany.
  • Wassim Gabriel
    Computational Mass Spectrometry, Technical University of Munich (TUM), D-85354 Freising, Germany.
  • Bernhard Kuster
    Chair for Proteomics and Bioanalytics, TU Muenchen, Freising 85354, Germany; German Cancer Consortium (DKTK), Munich, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Integrated Protein Science Munich, Munich, Germany; Bavarian Biomolecular Mass Spectrometry Center, Technische Universität München, Freising, Germany.
  • Mathias Wilhelm
    Chair for Proteomics and Bioanalytics, TU Muenchen, Freising 85354, Germany.