MSstatsBioNet: Integrating Statistical Analyses with Prior Knowledge Biomolecular Networks for Quantitative Proteomics and Phosphoproteomics

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

A common outcome of quantitative mass spectrometry-based proteomic and phosphoproteomic experiments is a list of proteins that are differentially abundant between conditions. However, biological interpretation requires evaluation in the context of prior knowledge of biological mechanisms and protein function. One approach to facilitate mechanistic biological interpretation is to integrate such lists with biological network databases, built from manually curated resources and text mining systems. This manuscript automates this process with MSstatsBioNet, a Bioconductor package that integrates MSstats, a family of open-source packages for detecting differentially abundant proteins, and INDRA, a system that extracts biomolecular networks from biomedical literature using text mining and merges those networks with the content of curated knowledge bases. Taking as input a list of differentially abundant proteins from MSstats, MSstatsBioNet retrieves a protein subnetwork from INDRA and overlays experimental fold changes onto the underlying subnetwork. Users can then interact with the network and overlaid data, interrogating primary literature evidence to construct granular mechanistic narratives for iterative hypothesis generation. We demonstrate the utility of this approach with three case studies, two measuring changes in protein abundance and one measuring changes in phosphorylation.

Authors 13

1. Anthony Wu

   Northeastern University

   Affiliation as printed

   Northeastern University;

2. Devon Kohler

   Northeastern University

   Affiliation as printed

   Northeastern University;

3. Pruthvi Prakash Navada

   Northeastern University

   Affiliation as printed

   Northeastern University;

4. Julia E. Robbins
   Affiliation as printed

   Talus Bioscience Inc.;

5. Gabriel E. Boyle

   Seattle Children's Hospital

   Affiliation as printed

   Seattle Children's Hospital;

6. Alex Boshart

   University of Toronto

   Affiliation as printed

   University of Toronto;

7. Klas Karis

   Northeastern University

   Affiliation as printed

   Northeastern University;

8. Jacques Neefjes Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center;

9. Ana Konvalinka

   Toronto General Hospital

   Affiliation as printed

   Toronto General Research Institute

10. Jay F. Sarthy

    Seattle Children's Hospital

    Affiliation as printed

    Seattle Children's Hospital;

11. Lindsay K. Pino
    Affiliation as printed

    Talus Bioscience Inc.;

12. Benjamin M. Gyori

    Northeastern University

    Affiliation as printed

    Northeastern University;

13. Olga Vitek corresponding

    Northeastern University

    Affiliation as printed

    Northeastern University;