Interactomics: toward protein function and regulation

Abstract

Protein–protein interactions are central to all cellular processes. Understanding of protein–protein interactions is therefore fundamental for many areas of biochemical and biomedical research and will facilitate an understanding of the cell process-regulating machinery, disease causative mechanisms, biomarkers, drug target discovery and drug development. In this review, we summarize methods for populating and analyzing the interactome, highlighting their advantages and disadvantages. Applications of interactomics in both the biochemical and clinical arenas are presented, illustrating important recent advances in the field.

Keywords:

• interactomics
• network analysis
• network hubs
• protein–protein interactions
• proteomics

Financial & competing interests disclosure

This work was financially supported by grants from the National 973 Basic Research Program of China (2013CB911300), Chinese NSFC (J1103518) and the Research Program of Science and Technology Department of Sichuan Provence, China (2014JY0043). The authors have no 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• As evidenced by the large number of recent publications, interactomics has become a dynamic and rapidly growing field of research with new paradigms in signaling emerging. Currently, over 170,000 human PPIs are registered in the Interologous Interaction Database (Table 1).

• A number of technologies have been adapted for detection of PPIs, including yeast two-hybrid, tandem affinity purification-mass spectrometry, the protein-fragment complementation assay, the luminescence-based mammalian interactome, protein microarrays and the mammalian protein–protein interaction trap.

• These methods can be roughly divided into three groups: in silico, in vivo and in vitro. Each group has both advantages and disadvantages.

• Similar techniques can be used to address other interacting biomolecular interactions including DNA, ligands for enzymes, transporters, receptors, metabolic networks, etc. It can also be applied to other systems (e.g., plants).

• Validation of experimentally acquired data is still a demanding procedure, as reliability, high false-positive rates, low coverage and difficulties in multiplexed quantification can hinder the construction of a reliable interactome. Orthogonal methods are required for extended coverage and validation.

• The focus on the differences between intermodular and intramodular hubs is an important new approach for analyzing an interactome.

• Protein interactome maps are proving extremely valuable for deciphering cell/disease biology and discovering new drug targets.

• Identifying subsets of disease-related proteins from interactomes should lead to novel biomarkers and biomarker panels.

Notes