Differential network analysis of multiple human tissue interactomes highlights tissue-selective processes and genetic disorder genes

Omer Basha, Chanan M. Argov, Raviv Artzy, Yazeed Zoabi, Idan Hekselman, Liad Alfandari, Vered Chalifa-Caspi, Esti Yeger-Lotem, Esti Yeger-Lotem

Research output: Contribution to journalArticlepeer-review

Abstract

Motivation: Differential network analysis, designed to highlight network changes between conditions, is an important paradigm in network biology. However, differential network analysis methods have been typically designed to compare between two conditions and were rarely applied to multiple protein interaction networks (interactomes). Importantly, large-scale benchmarks for their evaluation have been lacking. Results: Here, we present a framework for assessing the ability of differential network analysis of multiple human tissue interactomes to highlight tissue-selective processes and disorders. For this, we created a benchmark of 6499 curated tissue-specific Gene Ontology biological processes. We applied five methods, including four differential network analysis methods, to construct weighted interactomes for 34 tissues. Rigorous assessment of this benchmark revealed that differential analysis methods perform well in revealing tissue-selective processes (AUCs of 0.82-0.9). Next, we applied differential network analysis to illuminate the genes underlying tissue-selective hereditary disorders. For this, we curated a dataset of 1305 tissue-specific hereditary disorders and their manifesting tissues. Focusing on subnetworks containing the top 1% differential interactions in disease-relevant tissue interactomes revealed significant enrichment for disorder-causing genes in 18.6% of the cases, with a significantly high success rate for blood, nerve, muscle and heart diseases. Summary: Altogether, we offer a framework that includes expansive manually curated datasets of tissue-selective processes and disorders to be used as benchmarks or to illuminate tissue-selective processes and genes. Our results demonstrate that differential analysis of multiple human tissue interactomes is a powerful tool for highlighting processes and genes with tissue-selective functionality and clinical impact.

Original languageEnglish
Pages (from-to)2821-2828
Number of pages8
JournalBioinformatics
Volume36
Issue number9
DOIs
StatePublished - 1 May 2020
Externally publishedYes

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