In silico prediction of protein-protein interactions in human macrophages

TLDR

Protein‑protein interaction network analyses are valuable for deciphering cellular functions, yet most existing networks lack contextual information such as spatial, temporal, or physiological conditions. The study proposes a protocol to infer a macrophage‑specific protein‑protein interaction network. The protocol combines the APID PPI dataset with contextual metadata and statistical methods to construct a macrophage‑specific interactome. The inferred macrophage interactome is enriched in verified interactions and macrophage‑related proteins, and contextualization reveals immune processes such as apoptosis that are not apparent from gene expression alone, as demonstrated in a Mycobacterium tuberculosis infection case study.

Abstract

Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages.We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection.Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level.