ArticlePLoS genetics2016
Network Analysis of Genome-Wide Selective Constraint Reveals a Gene Network Active in Early Fetal Brain Intolerant of Mutation.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- NetMix: A Network-Structured Mixture Model for Reduced-Bias Estimation of Altered Subnetworks.Journal of computational biology : a journal of computational molecular cell biology · 2021Article
- Putative contributions of the sex chromosome proteins SOX3 and SRY to neurodevelopmental disorders.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2019Article
- A novel variant inNeuronal signaling · 2018Article
- Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development.Frontiers in genetics · 2018Article
- Large-Scale trans-eQTLs Affect Hundreds of Transcripts and Mediate Patterns of Transcriptional Co-regulation.American journal of human genetics · 2017Article
- Gene co-expression network connectivity is an important determinant of selective constraint.PLoS genetics · 2017Article
- Increased burden of deleterious variants in essential genes in autism spectrum disorder.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using robust, integrated analysis of multiple genomic datasets, we show that genes depleted for non-synonymous de novo mutations form a subnetwork of 72 members under strong selective constraint. We further show this subnetwork is preferentially expressed in the early development of the human hippocampus and is enriched for genes mutated in neurological Mendelian disorders. We thus conclude that carefully orchestrated developmental processes are under strong constraint in early brain development, and perturbations caused by mutation have adverse outcomes subject to strong purifying selection. Our findings demonstrate that selective forces can act on groups of genes involved in the same process, supporting the notion that purifying selection can act coordinately on multiple genes. Our approach provides a statistically robust, interpretable way to identify the tissues and developmental times where groups of disease genes are active.
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Registered trials
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