ArticleHuman molecular genetics2015
A disease module in the interactome explains disease heterogeneity, drug response and captures novel pathways and genes in asthma.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.
- Interactome-transcriptome analysis discovers signatures complementary to GWAS Loci of Type 2 Diabetes.Scientific reports · 2016Pooled it
- Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator.The Journal of allergy and clinical immunology · 2018Trial
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- The differential effects of cAMP mobilizing agents on TGF-β-induced extracellular matrix in human lung-derived fibroblasts: insights into therapeutic targets for lung fibrosis.Respiratory research · 2025Article
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- A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study.Frontiers in human neuroscience · 2025Article
- Neuroimmune dynamics and brain aging: mechanisms and consequences.Frontiers in aging neuroscience · 2025Review
- Latent space arithmetic on data embeddings from healthy multi-tissue human RNA-seq decodes disease modules.Patterns (New York, N.Y.) · 2024Article
- Disease gene prioritization with quantum walks.Bioinformatics (Oxford, England) · 2024Article
- Decoding the Foodome: Molecular Networks Connecting Diet and Health.Annual review of nutrition · 2024Review
- Non-Coding RNAs Extended Omnigenic Module of Cancers.Entropy (Basel, Switzerland) · 2024Article
- Uncovering the subtype-specific disease module and the development of drug response prediction models for glioma.Heliyon · 2024Article
- Strategic pathway analysis for dual management of epilepsy and comorbid depression: a systems biology perspective.In silico pharmacology · 2024Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 8 institutions in 2 countries.
Funding
Abstract
Recent advances in genetics have spurred rapid progress towards the systematic identification of genes involved in complex diseases. Still, the detailed understanding of the molecular and physiological mechanisms through which these genes affect disease phenotypes remains a major challenge. Here, we identify the asthma disease module, i.e. the local neighborhood of the interactome whose perturbation is associated with asthma, and validate it for functional and pathophysiological relevance, using both computational and experimental approaches. We find that the asthma disease module is enriched with modest GWAS P-values against the background of random variation, and with differentially expressed genes from normal and asthmatic fibroblast cells treated with an asthma-specific drug. The asthma module also contains immune response mechanisms that are shared with other immune-related disease modules. Further, using diverse omics (genomics, gene-expression, drug response) data, we identify the GAB1 signaling pathway as an important novel modulator in asthma. The wiring diagram of the uncovered asthma module suggests a relatively close link between GAB1 and glucocorticoids (GCs), which we experimentally validate, observing an increase in the level of GAB1 after GC treatment in BEAS-2B bronchial epithelial cells. The siRNA knockdown of GAB1 in the BEAS-2B cell line resulted in a decrease in the NFkB level, suggesting a novel regulatory path of the pro-inflammatory factor NFkB by GAB1 in asthma.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.