SynthesisGenome medicine2021
Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.
Synthesis in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.Genome medicine · 2021Pooled it
- Positive selection on brain cis-regulatory elements in the human lineage drives changes in gene expression and susceptibility to neuropsychiatric disorders.HGG advances · 2026Article
- CRISPR tiling deletion screens reveal functional enhancers and allelic compensation effects (ACE) on SIN3A transcription.Nature communications · 2026Article
- A clinical and genotype-phenotype analysis of MACF1 variants.American journal of human genetics · 2025Article
- NK/DC crosstalk-modulating antitumor activity via Sema3E/PlexinD1 axis for enhanced cancer immunotherapy.Immunologic research · 2024Review
- Identification and Copy Number Variant Analysis of Enhancer Regions of Genes Causing Spinocerebellar Ataxia.International journal of molecular sciences · 2024Article
- Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements.Science advances · 2024Article
- Lipotype acquisition during neural development is not recapitulated in stem cell-derived neurons.Life science alliance · 2024Article
- Genetic effects of sequence-conserved enhancer-like elements on human complex traits.Genome biology · 2024Article
- Integrative computational analyses implicate regulatory genomic elements contributing to spina bifida.Genetics in medicine open · 2024Article
- MYT1L is required for suppressing earlier neuronal development programs in the adult mouse brain.Genome research · 2023Article
- Editorial: Pathogenic mechanisms in neurodevelopmental disorders: advances in cellular models and multi-omics approaches.Frontiers in cell and developmental biology · 2023Article
- Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex.Genome medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNon-coding regulatory elements (NCREs), such as enhancers, play a crucial role in gene regulation, and genetic aberrations in NCREs can lead to human disease, including brain disorders. The human brain is a complex organ that is susceptible to numerous disorders; many of these are caused by genetic changes, but a multitude remain currently unexplained. Understanding NCREs acting during brain development has the potential to shed light on previously unrecognized genetic causes of human brain disease. Despite immense community-wide efforts to understand the role of the non-coding genome and NCREs, annotating functional NCREs remains challenging.
methodsHere we performed an integrative computational analysis of virtually all currently available epigenome data sets related to human fetal brain.
resultsOur in-depth analysis unravels 39,709 differentially active enhancers (DAEs) that show dynamic epigenomic rearrangement during early stages of human brain development, indicating likely biological function. Many of these DAEs are linked to clinically relevant genes, and functional validation of selected DAEs in cell models and zebrafish confirms their role in gene regulation. Compared to enhancers without dynamic epigenomic rearrangement, DAEs are subjected to higher sequence constraints in humans, have distinct sequence characteristics and are bound by a distinct transcription factor landscape. DAEs are enriched for GWAS loci for brain-related traits and for genetic variation found in individuals with neurodevelopmental disorders, including autism.
conclusionThis compendium of high-confidence enhancers will assist in deciphering the mechanism behind developmental genetics of human brain and will be relevant to uncover missing heritability in human genetic brain disorders.
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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.