HIR V2: a human interactome resource for the biological interpretation of differentially expressed genes via gene set linkage analysis

Abstract

To facilitate biomedical studies of disease mechanisms, a high-quality interactome that connects functionally related genes is needed to help investigators formulate pathway hypotheses and to interpret the biological logic of a phenotype at the biological process level. Interactions in the updated version of the human interactome resource (HIR V2) were inferred from 36 mathematical characterizations of six types of data that suggest functional associations between genes. This update of the HIR consists of 88 069 pairs of genes (23.2% functional interactions of HIR V2 are in common with the previous version of HIR), representing functional associations that are of strengths similar to those between well-studied protein interactions. Among these functional interactions, 57% may represent protein interactions, which are expected to cover 32% of the true human protein interactome. The gene set linkage analysis (GSLA) tool is developed based on the high-quality HIR V2 to identify the potential functional impacts of the observed transcriptomic changes, helping to elucidate their biological significance and complementing the currently widely used enrichment-based gene set interpretation tools. A case study shows that the annotations reported by the HIR V2/GSLA system are more comprehensive and concise compared to those obtained by the widely used gene set annotation tools such as PANTHER and DAVID. The HIR V2 and GSLA are available at http://human.biomedtzc.cn.

Genome-wide association studies of human and rat BMI converge on synapse, epigenome, and hormone signaling networks

“…Although many genes and cellular processes are similar between humans and other mammals, the mapping of orthologous genes is imperfect, and gene and protein interaction patterns can vary between species due to the rewiring of regulatory and protein-protein interaction networks. 33 , 77 , 78 For this reason, work is ongoing to generate independent molecular interaction networks for mammalian species, including mice, 79 rats, 80 and cattle. 81 Network rewiring of interactions also occurs in different tissues and cell types.…”

Comparative co-expression analysis of RNA-Seq transcriptome revealing key genes, miRNA and transcription factor in distinct metabolic pathways in diabetic nerve, eye, and kidney disease

“…The gene set linkage analysis (GSLA) tool in Human Interactome Resource (HIR) was used to analyze the gene sets of interest [ 22 ]. The higher the density greater the link of the gene to the pathway or network.…”

Viral Targets in Human Interactome with Comprehensive Centrality Analysis: SARS-CoV-2, A Case Study

“…Among these varied resources, the STRING database [33] emerged as pivotal, containing A vast repository of 561,769 experimentally validated interactions involving approximately 18,000 proteins (Figure 1A and B and Table S1). Additionally, we curated PPI data from additional proteome-scale interactome studies, namely Human Interactome I and II, BioPlex, QUBIC, and CoFrac (as reviewed in [34]), alongside contributions from the Human Interactome Resource (HIR) [35] (Figure 1A and B and Table S1). Following the integration of these diverse PPI datasets, our resultant integrated human interactome featured 825,682 interactions and 26,000 nodes.…”