DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery

Genomics Proteomics Bioinformatics. 2020 Apr;18(2):104-119. doi: 10.1016/j.gpb.2019.11.008. Epub 2020 Aug 12.

Abstract

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Keywords: Data-independent acquisition; Diffuse large B cell lymphoma; Parallel reaction monitoring; Prostate cancer; Spectral library.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / blood
  • Cell Line, Tumor
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Male
  • Mass Spectrometry*
  • Neoplasm Proteins / analysis
  • Peptides / metabolism
  • Prostatic Neoplasms / metabolism
  • Proteomics
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Peptides