ArticleGenome research2006
Close sequence comparisons are sufficient to identify human cis-regulatory elements.
Article in Genome research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis 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.
The trial behind it
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.
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Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- A meta-analysis of microarray gene expression in mouse stem cells: redefining stemness.PloS one · 2008Pooled it
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- Conserved Noncoding Elements Evolve Around the Same Genes Throughout Metazoan Evolution.Genome biology and evolution · 2024Article
- The Goldfish Genome and Its Utility for Understanding Gene Regulation and Vertebrate Body Morphology.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Review
- Perfect and imperfect views of ultraconserved sequences.Nature reviews. Genetics · 2022Review
- A Comparative Analysis of Super-Enhancers and Broad H3K4me3 Domains in Pig, Human, and Mouse Tissues.Frontiers in genetics · 2021Article
- Broadening primate genomics: new insights into the ecology and evolution of primate gene regulation.Current opinion in genetics & development · 2020Review
- Predicting enhancers in mammalian genomes using supervised hidden Markov models.BMC bioinformatics · 2019Article
- Functional conservation of sequence determinants at rapidly evolving regulatory regions across mammals.PLoS computational biology · 2018Article
- Investigating transcription factor synergism in humans.DNA research : an international journal for rapid publication of reports on genes and genomes · 2018Article
- Putative enhancer sites in the bovine genome are enriched with variants affecting complex traits.Genetics, selection, evolution : GSE · 2017Article
- Differential Gene Expression in the Human Brain Is Associated with Conserved, but Not Accelerated, Noncoding Sequences.Molecular biology and evolution · 2017Article
- EnhancerPred: a predictor for discovering enhancers based on the combination and selection of multiple features.Scientific reports · 2016Article
- First insights into the nature and evolution of antisense transcription in nematodes.BMC evolutionary biology · 2016Article
- PEDLA: predicting enhancers with a deep learning-based algorithmic framework.Scientific reports · 2016Article
- Origin and evolution of developmental enhancers in the mammalian neocortex.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Elucidating the mechanisms of transcription regulation during heart development by next-generation sequencing.Journal of human genetics · 2016Review
- Can a few non-coding mutations make a human brain?BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Article
- Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of evolutionarily close and distant sequence comparisons. To address this problem, we identified evolutionarily conserved noncoding regions in primate, mammalian, and more distant comparisons using a uniform approach (Gumby) that facilitates unbiased assessment of the impact of evolutionary distance on predictive power. We benchmarked computational predictions against previously identified cis-regulatory elements at diverse genomic loci and also tested numerous extremely conserved human-rodent sequences for transcriptional enhancer activity using an in vivo enhancer assay in transgenic mice. Human regulatory elements were identified with acceptable sensitivity (53%-80%) and true-positive rate (27%-67%) by comparison with one to five other eutherian mammals or six other simian primates. More distant comparisons (marsupial, avian, amphibian, and fish) failed to identify many of the empirically defined functional noncoding elements. Our results highlight the practical utility of close sequence comparisons, and the loss of sensitivity entailed by more distant comparisons. We derived an intuitive relationship between ancient and recent noncoding sequence conservation from whole-genome comparative analysis that explains most of the observations from empirical benchmarking. Lastly, we determined that, in addition to strength of conservation, genomic location and/or density of surrounding conserved elements must also be considered in selecting candidate enhancers for in vivo testing at embryonic time points.
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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.