ArticleAmerican journal of human genetics2016
Complex Sources of Variation in Tissue Expression Data: Analysis of the GTEx Lung Transcriptome.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Machine Learning based histology phenotyping to investigate the epidemiologic and genetic basis of adipocyte morphology and cardiometabolic traits.PLoS computational biology · 2020Pooled it
- Intra-individual Gene Expression Variability of Histologically Normal Breast Tissue.Scientific reports · 2018Trial
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- Inter-individual gene expression variability implies stable regulation of brain-biased genes across organs in three ray-finned fishes.bioRxiv : the preprint server for biology · 2026Article
- Population-based genome-wide association study of plasma complex lipid species.Nature communications · 2026Article
- Cell type heterogeneity in gene co-expression networks: implications for toxicological research.Briefings in bioinformatics · 2025Review
- Differential causal networks highlight sex-based differences in human tissues.Briefings in bioinformatics · 2025Article
- Identifying reproducible transcription regulator coexpression patterns with single cell transcriptomics.PLoS computational biology · 2025Article
- Transcriptome-Wide Association Study of Idiopathic Pulmonary Fibrosis Survival IdentifiesAmerican journal of respiratory and critical care medicine · 2024Article
- Patterns of Unwanted Biological and Technical Expression Variation Among 49 Human Tissues.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- voyAGEr, a free web interface for the analysis of age-related gene expression alterations in human tissues.eLife · 2024Article
- Genetic Variants at PRKCG Splice and UTR Sites Promote Cancer Susceptibility by Disrupting Epigenetic and miRNA Regulatory Network.Journal of Cancer · 2024Article
- Release of Pro-Inflammatory/Angiogenic Factors by Retinal Microvascular Cells Is Mediated by Extracellular Vesicles Derived from M1-Activated Microglia.International journal of molecular sciences · 2023Article
- Shared regulation and functional relevance of local gene co-expression revealed by single cell analysis.Communications biology · 2022Article
- Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program.American journal of human genetics · 2022Article
- Integrative Prioritization of Causal Genes for Coronary Artery Disease.Circulation. Genomic and precision medicine · 2022Article
- Article
- Tissue, age, sex, and disease patterns of matrisome expression in GTEx transcriptome data.Scientific reports · 2021Article
- Article
- Single-cell co-expression analysis reveals that transcriptional modules are shared across cell types in the brain.Cell systems · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The sources of gene expression variability in human tissues are thought to be a complex interplay of technical, compositional, and disease-related factors. To better understand these contributions, we investigated expression variability in a relatively homogeneous tissue expression dataset from the Genotype-Tissue Expression (GTEx) resource. In addition to identifying technical sources, such as sequencing date and post-mortem interval, we also identified several biological sources of variation. An in-depth analysis of the 175 genes with the greatest variation among 133 lung tissue samples identified five distinct clusters of highly correlated genes. One large cluster included surfactant genes (SFTPA1, SFTPA2, and SFTPC), which are expressed exclusively in type II pneumocytes, cells that proliferate in ventilator associated lung injury. High surfactant expression was strongly associated with death on a ventilator and type II pneumocyte hyperplasia. A second large cluster included dynein (DNAH9 and DNAH12) and mucin (MUC5B and MUC16) genes, which are exclusive to the respiratory epithelium and goblet cells of bronchial structures. This indicates heterogeneous bronchiole sampling due to the harvesting location in the lung. A small cluster included acute-phase reactant genes (SAA1, SAA2, and SAA2-SAA4). The final two small clusters were technical and gender related. To summarize, in a collection of normal lung samples, we found that tissue heterogeneity caused by harvesting location (medial or lateral lung) and late therapeutic intervention (mechanical ventilation) were major contributors to expression variation. These unexpected sources of variation were the result of altered cell ratios in the tissue samples, an underappreciated source of expression variation.
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