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Updated: Feb 20, 2026

Mapping Dysfunctional Protein-Protein Interactions in Disease
Published on: October 24, 2025
The DifferentialNet database of differential protein-protein interactions in human tissues
Omer Basha1, Rotem Shpringer1, Chanan M Argov1
1Department of Clinical Biochemistry & Pharmacology, Faculty of Health Sciences.
Abstract:
DifferentialNet is a novel database that provides users with differential interactome analysis of human tissues (http://netbio.bgu.ac.il/diffnet/). Users query DifferentialNet by protein, and retrieve its differential protein-protein interactions (PPIs) per tissue via an interactive graphical interface. To compute differential PPIs, we integrated available data of experimentally detected PPIs with RNA-sequencing profiles of tens of human tissues gathered by the Genotype-Tissue Expression consortium (GTEx) and by the Human Protein Atlas (HPA). We associated each PPI with a score that reflects whether its corresponding genes were expressed similarly across tissues, or were up- or down-regulated in the selected tissue. By this, users can identify tissue-specific interactions, filter out PPIs that are relatively stable across tissues, and highlight PPIs that show relative changes across tissues. The differential PPIs can be used to identify tissue-specific processes and to decipher tissue-specific phenotypes. Moreover, they unravel processes that are tissue-wide yet tailored to the specific demands of each tissue.
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