ArticleNature communications2024
Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Alignment-free integration of single-nucleus ATAC-seq across species with sPYce.Nature ecology & evolution · 2026Article
- The Encyclopedia of DNA Elements.bioRxiv : the preprint server for biology · 2026Article
- Evolutionary transfer learning enables organism-wide inference of mammalian enhancer landscapes.bioRxiv : the preprint server for biology · 2026Article
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Retracing and rewriting the evolutionary trajectories of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Decoding cell-class specific roles of non-coding variants in human retina.Scientific reports · 2025Article
- Conservation of regulatory elements with highly diverged sequences across large evolutionary distances.Nature genetics · 2025Article
- Non-local modeling of enhancer-promoter interactions, a correspondence on "LOCO-EPI: Leave-one-chromosome-out (LOCO) as a benchmarking paradigm for deep learning based prediction of enhancer-promoter interactions".Applied intelligence (Dordrecht, Netherlands) · 2025Article
- Machine Learning Prediction of Non-Coding Variant Impact in Cell-Class-Specific Human RetinalbioRxiv : the preprint server for biology · 2025Article
- Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals.Nature communications · 2024Article
- Extreme restructuring of cis-regulatory regions controlling a deeply conserved plant stem cell regulator.PLoS genetics · 2024Article
- MicroRNAs provide negative feedback and stability in gene regulatory network models of cell-state transitions.Frontiers in epigenetics and epigenomics · 2024Article
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2 authors.
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Abstract
Gene regulatory elements drive complex biological phenomena and their mutations are associated with common human diseases. The impacts of human regulatory variants are often tested using model organisms such as mice. However, mapping human enhancers to conserved elements in mice remains a challenge, due to both rapid enhancer evolution and limitations of current computational methods. We analyze distal enhancers across 45 matched human/mouse cell/tissue pairs from a comprehensive dataset of DNase-seq experiments, and show that while cell-specific regulatory vocabulary is conserved, enhancers evolve more rapidly than promoters and CTCF binding sites. Enhancer conservation rates vary across cell types, in part explainable by tissue specific transposable element activity. We present an improved genome alignment algorithm using gapped-kmer features, called gkm-align, and make genome wide predictions for 1,401,803 orthologous regulatory elements. We show that gkm-align discovers 23,660 novel human/mouse conserved enhancers missed by previous algorithms, with strong evidence of conserved functional activity.
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