Adding biological meaning to human protein-protein interactions identified by yeast two-hybrid screenings: A guide through bioinformatics tools

• Published in: Journal of proteomics Vol. 171; pp. 127 - 140
• Main Authors: Felgueiras, Juliana, Silva, Joana Vieira, Fardilha, Margarida
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 16-01-2018
• Subjects: Computational Biology - methods; Databases, Protein; Humans; ontology; Organ Specificity; pathways; phenotypes; Protein Interaction Maps; Protein-protein interaction networks; Proteins - genetics; Proteins - metabolism; Proteome - metabolism; Signal Transduction; tissue expression; Transcriptome; Two-Hybrid System Techniques; PPIN; RefSeq; APP; LSID; WGS; IPI; PPI; PTM; HTT; SEGUID; PDB; EMBL; STS; PSI-MI; CASP6; DDBJ; NCBI; TCTEX1D4; Protein-protein interaction networks; ontology; MIMIx; databases; TSA; pathways; Co-IP; Y2H; MIM; phenotypes; tissue expression; HD; PCR; CRM
• ISSN: 1874-3919; 1876-7737
• DOI: 10.1016/j.jprot.2017.05.012

“A man is known by the company he keeps” is a popular expression that perfectly fits proteins. A common approach to characterize the function of a target protein is to identify its interacting partners and thus infer its roles based on the known functions of the interactors. Protein-protein interaction networks (PPINs) have been created for several organisms, including humans, primarily as results of high-throughput screenings, such as yeast two-hybrid (Y2H). Their unequivocal use to understand events underlying human pathophysiology is promising in identifying genes and proteins associated with diseases. Therefore, numerous opportunities have emerged for PPINs as tools for clinical management of diseases: network-based disease classification systems, discovery of biomarkers and identification of therapeutic targets. Despite the great advantages of PPINs, their use is still unrecognised by several researchers who generate high-throughput data to generally characterize interactions in a certain model or to select an interaction to study in detail. We strongly believe that both approaches are not exclusive and that we can use PPINs as a complementary methodology and rich-source of information to the initial study proposal. Here, we suggest a pipeline to deal with Y2H results using bioinformatics tools freely available for academics.
Yeast two-hybrid is widely-used to identify protein-protein interactions. Conventionally, the positive clones that result from a yeast two-hybrid screening are sequenced to identify the interactors of the protein of interest (also known as bait protein), and few interactions, thought as potentially relevant for the model in study, are selected for further validation using biochemical methods (e.g. co-immunoprecipitation and co-localization). The huge amount of data that is potentially lost during this conservative approach motivated us to write this tutorial-like review, so that researchers feel encouraged to take advantage of bioinformatics tools to their full potential to analyse protein-protein interactions as a comprehensive network.
General workflow to explore yeast two-hybrid results using bioinformatics tools. Figures were produced using Servier Medical Art from www.servier.com. [Display omitted]
•Y2H screenings can generate large amounts of data.•Bioinformatics analysis empowers the understanding of protein interactomes.•Bioinformatics tools and repositories are available to construct and enrich PPINs.•Functional annotation provides biological significance to PPINs.•Expression data and association with phenotypes/disease can be integrated in PPINs.