ArticlePLoS computational biology2014
Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Interactome-transcriptome analysis discovers signatures complementary to GWAS Loci of Type 2 Diabetes.Scientific reports · 2016Pooled it
- Human genetics across levels of biological organization.Nature reviews. Genetics · 2026Review
- Why are Some Tissues More Vulnerable? Revisiting Tissue Specificity in Hereditary Cancer Syndromes.Molecular diagnosis & therapy · 2026Review
- LncRNA-Mediated Tissue-Specific Plastic Responses to Salinity Changes in Oysters.International journal of molecular sciences · 2025Article
- Differential expression and co-expression reveal cell types relevant to genetic disorder phenotypes.Bioinformatics (Oxford, England) · 2024Article
- Tissue-aware interpretation of genetic variants advances the etiology of rare diseases.Molecular systems biology · 2024Article
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- Predicting molecular mechanisms of hereditary diseases by using their tissue-selective manifestation.Molecular systems biology · 2023Article
- Splicing Modulators Are Involved in Human Polyglutamine Diversification via Protein Complexes Shuttling between Nucleus and Cytoplasm.International journal of molecular sciences · 2023Article
- Review
- Tissue Specificity of Gene Expression Evolves Across Mammal Species.Journal of computational biology : a journal of computational molecular cell biology · 2022Article
- Disease-specific interactome alterations via epichaperomics: the case for Alzheimer's disease.The FEBS journal · 2022Review
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- Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease.Computational and structural biotechnology journal · 2022Article
- The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones.Nature communications · 2021Article
- An analytical method for the identification of cell type-specific disease gene modules.Journal of translational medicine · 2021Article
- Detecting Rewiring Events in Protein-Protein Interaction Networks Based on Transcriptomic Data.Frontiers in bioinformatics · 2021Review
- Exploring Drug Treatment Patterns Based on the Action of Drug and Multilayer Network Model.International journal of molecular sciences · 2020Article
- Precision medicine - networks to the rescue.Current opinion in biotechnology · 2020Review
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases, which are caused by genomic aberrations that are present in cells across the human body. Here we analyzed this phenomenon for over 300 hereditary diseases by using comparative network analysis. We created an extensive resource of protein expression and interactions in 16 main human tissues, by integrating recent data of gene and protein expression across tissues with data of protein-protein interactions (PPIs). The resulting tissue interaction networks (interactomes) shared a large fraction of their proteins and PPIs, and only a small fraction of them were tissue-specific. Applying this resource to hereditary diseases, we first show that most of the disease-causing genes are widely expressed across tissues, yet, enigmatically, cause disease phenotypes in few tissues only. Upon testing for factors that could lead to tissue-specific vulnerability, we find that disease-causing genes tend to have elevated transcript levels and increased number of tissue-specific PPIs in their disease tissues compared to unaffected tissues. We demonstrate through several examples that these tissue-specific PPIs can highlight disease mechanisms, and thus, owing to their small number, provide a powerful filter for interrogating disease etiologies. As two thirds of the hereditary diseases are associated with these factors, comparative tissue analysis offers a meaningful and efficient framework for enhancing the understanding of the molecular basis of hereditary diseases.
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