Protein complexes, big data, machine learning and integrative proteomics: lessons learned over a decade of systematic analysis of protein interaction networks

ABSTRACT

Overview: Elucidation of the networks of physical (functional) interactions present in cells and tissues is fundamental for understanding the molecular organization of biological systems, the mechanistic basis of essential and disease-related processes, and for functional annotation of previously uncharacterized proteins (via guilt-by-association or -correlation). After a decade in the field, we felt it timely to document our own experiences in the systematic analysis of protein interaction networks.

Areas covered: Researchers worldwide have contributed innovative experimental and computational approaches that have driven the rapidly evolving field of ‘functional proteomics’. These include mass spectrometry-based methods to characterize macromolecular complexes on a global-scale and sophisticated data analysis tools – most notably machine learning – that allow for the generation of high-quality protein association maps.

Expert commentary: Here, we recount some key lessons learned, with an emphasis on successful workflows, and challenges, arising from our own and other groups’ ongoing efforts to generate, interpret and report proteome-scale interaction networks in increasingly diverse biological contexts.

KEYWORDS:

• Macromolecular complex
• functional proteomics
• interactome
• machine learning
• mass spectrometry
• network
• prediction
• protein interaction
• scoring
• systems biology

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

Work summarized in this review was supported in part by grants from the Canadian Foundation for Innovation, Genome Canada and the Ontario Genomics Institute, and the Canadian Institutes for Health Research to A. Emili, by a studentship award from the University of Toronto Open Graduate Student Fellowship to P.C. Havugimana, and from the Manitoba Research Health Council Establishment Grant and University of Manitoba to P. Hu.