ArticleGenome biology2017
Systems-epigenomics inference of transcription factor activity implicates aryl-hydrocarbon-receptor inactivation as a key event in lung cancer development.
Article in Genome biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- A cell-type deconvolution meta-analysis of whole blood EWAS reveals lineage-specific smoking-associated DNA methylation changes.Nature communications · 2020Pooled it
- Appraising the causal relevance of DNA methylation for risk of lung cancer.International journal of epidemiology · 2019Pooled it
- Probing transcription factor subsets in gene regulatory networks.Algorithms for molecular biology : AMB · 2026Article
- Loss of coordination between basic cellular processes in human aging.Nature aging · 2024Article
- An improved epigenetic counter to track mitotic age in normal and precancerous tissues.Nature communications · 2024Article
- On epigenetic stochasticity, entropy and cancer risk.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Significance ofInternational journal of medical sciences · 2024Article
- GOAT: Gene-level biomarker discovery from multi-Omics data using graph ATtention neural network for eosinophilic asthma subtype.Bioinformatics (Oxford, England) · 2023Article
- Identifying genetic regulatory variants that affect transcription factor activity.Cell genomics · 2023Article
- AhR Promotes the Development of Non-small cell lung cancer by Inducing SLC7A11-dependent Antioxidant Function.Journal of Cancer · 2023Article
- Article
- Inference of age-associated transcription factor regulatory activity changes in single cells.Nature aging · 2022Article
- Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells.BMC pharmacology & toxicology · 2022Article
- Quantifying smoking exposure, genomic correlates, and related risk of treatment failure in p16+ squamous cell carcinoma of the oropharynx.Laryngoscope investigative otolaryngology · 2021Article
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Loss of Aryl Hydrocarbon Receptor FavorsCancers · 2021Article
- Inferring TF activities and activity regulators from gene expression data with constraints from TF perturbation data.Bioinformatics (Oxford, England) · 2021Article
- DNA Methylation Markers in Lung Cancer.Current genomics · 2021Review
- Integrative Molecular Analyses of an Individual Transcription Factor-Based Genomic Model for Lung Cancer Prognosis.Disease markers · 2021Article
- Dysregulation of Transcription Factor Activity During Formation of Cancer-Associated Fibroblasts.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundDiverse molecular alterations associated with smoking in normal and precursor lung cancer cells have been reported, yet their role in lung cancer etiology remains unclear. A prominent example is hypomethylation of the aryl hydrocarbon-receptor repressor (AHRR) locus, which is observed in blood and squamous epithelial cells of smokers, but not in lung cancer.
resultsUsing a novel systems-epigenomics algorithm, called SEPIRA, which leverages the power of a large RNA-sequencing expression compendium to infer regulatory activity from messenger RNA expression or DNA methylation (DNAm) profiles, we infer the landscape of binding activity of lung-specific transcription factors (TFs) in lung carcinogenesis. We show that lung-specific TFs become preferentially inactivated in lung cancer and precursor lung cancer lesions and further demonstrate that these results can be derived using only DNAm data. We identify subsets of TFs which become inactivated in precursor cells. Among these regulatory factors, we identify AHR, the aryl hydrocarbon-receptor which controls a healthy immune response in the lung epithelium and whose repressor, AHRR, has recently been implicated in smoking-mediated lung cancer. In addition, we identify FOXJ1, a TF which promotes growth of airway cilia and effective clearance of the lung airway epithelium from carcinogens.
conclusionsWe identify TFs, such as AHR, which become inactivated in the earliest stages of lung cancer and which, unlike AHRR hypomethylation, are also inactivated in lung cancer itself. The novel systems-epigenomics algorithm SEPIRA will be useful to the wider epigenome-wide association study community as a means of inferring regulatory activity.
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