ReviewProceedings of the National Academy of Sciences of the United States of America2014
Defining functional DNA elements in the human genome.
Review in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 373 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
373 citing papers in PubMed, 2 syntheses or guidelines pooled it, 743 citations in OpenAlex.
- Pooled it
- A Review of Statistical Methods for Identifying Trait-Relevant Tissues and Cell Types.Frontiers in genetics · 2020Pooled it
- Genomic indicators of gene function: a systematic assessment of the human genome.G3 (Bethesda, Md.) · 2026Article
- A novel dual-locus genotyping approach reveals epidemiological characteristics ofFood and waterborne parasitology · 2026Article
- Reference Regulatory Element-Guided Gene Expression Analysis for Mechanistic Inference of Gene Regulatory Networks.bioRxiv : the preprint server for biology · 2026Article
- Pervasive cryptic selection in the human noncoding genome.bioRxiv : the preprint server for biology · 2026Article
- Solid Tumors Pan Cancer Transcriptome: Tissue/Cancer specific expression groups at the Isoform-Level.bioRxiv : the preprint server for biology · 2026Article
- Pervasive Transcription in the Human Genome Exceeds Background Noise.Genome biology and evolution · 2026Article
- Therapeutic microRNAs: Mechanisms, Delivery, and Clinical Translation in Oncology.International journal of molecular sciences · 2026Review
- One Biology and the Status of Humans.Animals : an open access journal from MDPI · 2025Review
- Understanding Functional Evolution in Orthologs and Paralogs.Journal of molecular evolution · 2025Review
- Omnireg-gpt: a high-efficiency foundation model for comprehensive genomic sequence understanding.Nature communications · 2025Article
- Genomic structural equation modeling uncovers novel risk loci for bone metabolic disorders: cross-tissue genetic mechanisms and bone-brain axis regulation.BMC musculoskeletal disorders · 2025Article
- Comprehensive evaluation of diverse massively parallel reporter assays to functionally characterize human enhancers genome-wide.Genome biology · 2025Article
- Genomic structural equation modeling decodes skeletal aging: novel loci discovery and multisystem genetic crosstalk.Journal of translational medicine · 2025Article
- De Novo Gene Emergence: Summary, Classification, and Challenges of Current Methods.Genome biology and evolution · 2025Review
- Resequencing of two elite sorghum (Sorghum bicolor (L.) Moench) hybrid parent lines reveals distinctly different genome-wide variation models.Scientific reports · 2025Article
- varCADD: large sets of standing genetic variation enable genome-wide pathogenicity prediction.Genome medicine · 2025Article
- Integrating Intermediate Traits in Phylogenetic Genotype-to-Phenotype Studies.Integrative and comparative biology · 2025Review
- Klf5-adjacent super-enhancer functions as a 3D genome structure-dependent transcriptional driver to safeguard ESC identity.Nature communications · 2025Article
313 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 20 institutions in 3 countries.
Funding
Abstract
With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease.
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Registered trials
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.