A streamlined platform for analyzing tera-scale DDA and DIA mass spectrometry data enables highly sensitive immunopeptidomics

peer-reviewed · Nature Communications · 2022

peer-reviewed · Nature Communications · 2022. Lei Xin et al. Integrating data-dependent acquisition (DDA) and data-independent acquisition (DIA) approaches can enable…
Date 2022-06-07
Type peer-reviewed
Venue Nature Communications
Publisher Springer Science and Business Media LLC
Contribution algorithm
DOI 10.1038/s41467-022-30867-7
Citations (OpenAlex) 111
Venue 2-year citedness 17.60

Abstract

Integrating data-dependent acquisition (DDA) and data-independent acquisition (DIA) approaches can enable highly sensitive mass spectrometry, especially for imunnopeptidomics applications. Here we report a streamlined platform for both DDA and DIA data analysis. The platform integrates deep learning-based solutions of spectral library search, database search, and de novo sequencing under a unified framework, which not only boosts the sensitivity but also accurately controls the specificity of peptide identification. Our platform identifies 5-30% more peptide precursors than other state-of-the-art systems on multiple benchmark datasets. When evaluated on immunopeptidomics datasets, we identify 1.7-4.1 and 1.4-2.2 times more peptides from DDA and DIA data, respectively, than previously reported results. We also discover six T-cell epitopes from SARS-CoV-2 immunopeptidome that might represent potential targets for COVID-19 vaccine development. The platform supports data formats from all major instruments and is implemented with the distributed high-performance computing technology, allowing analysis of tera-scale datasets of thousands of samples for clinical applications.

Authors

  1. Lei Xin · Bioinformatics Solutions (Canada), Bioinformatics Solutions Inc., Western University
  2. Rui Qiao · Bioinformatics Solutions (Canada), Bioinformatics Solutions Inc., University of Waterloo
  3. Xin Chen (Waterloo) · Bioinformatics Solutions (Canada), Bioinformatics Solutions Inc.
  4. Ngoc Hieu Tran · Bioinformatics Solutions (Canada), Bioinformatics Solutions Inc., University of Waterloo
  5. Shengying Pan · Bioinformatics Solutions (Canada), Bioinformatics Solutions Inc.
  6. Sahar Rabinoviz · Bioinformatics Solutions (Canada)
  7. Haibo Bian · Bioinformatics Solutions (Canada)
  8. Xianliang He · Bioinformatics Solutions (Canada)
  9. Brenton Morse · Bioinformatics Solutions (Canada)
  10. Baozhen Shan · Bioinformatics Solutions (Canada), Bioinformatics Solutions Inc., Western University
  11. Ming Li · Bioinformatics Solutions Inc., Central China Institute of Artificial Intelligence, Peng Cheng Laboratory, University of Waterloo, University of Western Ontario

Methods and tools

  • PEAKS: Commercial DP-based de novo

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