Abstract
Proteins rarely carry out their cellular functions in isolation. Instead, eukaryotic proteins engage in about six interactions with other proteins on average. The aggregated protein interactome of an organism forms a “hairy ball”-type protein-protein interaction (PPI) network. Yet, in a typical human cell, only about half of all proteins are expressed at a particular time. Hence, it has become common practice to prune the full PPI network to the subset of expressed proteins. If RNAseq data is available, one can further resolve the specific protein isoforms present in a cell or tissue. Here, we review various approaches, software tools and webservices that enable users to construct context-specific or tissue-specific PPI networks and how these are rewired between two cellular conditions. We illustrate their different functionalities on the example of the interactions involving the human TNR6 protein. In an outlook, we describe how PPI networks may be integrated with epigenetic data or with data on the activity of splicing factors.
Highlights
Protein-protein interaction (PPI) networks are a popular cornerstone of integrative or computational cell biology and are frequently used to interpret the findings from high-throughput studies (Koh et al, 2012; Sevimoglu and Arga, 2014; Szklarczyk et al, 2019)
Some of the earliest established primary protein-protein interaction (PPI) resources that cover a wide range of species are the Biomolecular Interaction Network Database (BIND) (Bader et al, 2003), the Database of Interacting Proteins (DIP) (Salwinski et al, 2004), the Molecular Interaction Database (MINT) (Licata et al, 2012), TABLE 1 | Overview of PPI databases and PPI network (PPIN) features of their webservice
PPI data provided by Interactions Database (IID) is used by resources such as pathDIP (Rahmati et al, 2020), which predicts physical pathway associations for proteins based on physical species-specific protein interactions, or the interactive online platform CoVex (Sadegh et al, 2020), which facilitates exploration of the SARS-CoV-2 host interactome
Summary
Protein-protein interaction (PPI) networks are a popular cornerstone of integrative or computational cell biology and are frequently used to interpret the findings from high-throughput studies (Koh et al, 2012; Sevimoglu and Arga, 2014; Szklarczyk et al, 2019). We first give an overview of the numerous protein-level PPI databases that underpin the research effort in this field These databases were recently reviewed in a comprehensive manner (Bajpai et al, 2020) and we will focus on a few popular meta webservices that offer integrated analyses and the ability to tailor full PPI networks to a particular cellular context. Afterwards, we present those tools and webservices in detail that support isoform-level analysis of protein interactions. Some of the earliest established primary PPI resources that cover a wide range of species are the Biomolecular Interaction Network Database (BIND) (Bader et al, 2003), the Database of Interacting Proteins (DIP) (Salwinski et al, 2004), the Molecular Interaction Database (MINT) (Licata et al, 2012),
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