Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory
Henry E Pratt1, Gregory Andrews1, Nicole Shedd1
1Department of Genomics and Computational Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Science Advances
|May 23, 2024
Summary
Researchers mapped brain regulatory elements linked to psychiatric disorders, revealing that new genetic information arises from mutations in conserved sequences. Primate-specific elements are crucial for fetal brain development and human traits.
Area of Science:
- Genomics and Neurobiology
- Computational Biology and Bioinformatics
Background:
- Most genetic variants for psychiatric disorders reside in noncoding DNA.
- Understanding the function of these noncoding variants is crucial for psychiatric disorder research.
Purpose of the Study:
- To create an atlas of candidate brain cis-regulatory elements.
- To investigate the role of these elements in cell type-specific gene regulation.
- To explore the evolutionary origins of regulatory elements and their link to psychiatric disorder heritability.
Main Methods:
- Integration of epigenetic data from the PsychENCODE Consortium and other sources.
- Application of deep learning to model sequence syntax and predict transcription factor binding.
- Analysis of evolutionary history of regulatory elements.
- Introduction of the PsychSCREEN web platform for data visualization.
Main Results:
- A comprehensive atlas of candidate brain cis-regulatory elements was constructed.
- Deep learning models predicted cell type-specific gene regulation by transcription factors.
- Evolutionary analysis indicated new brain regulatory information arises from mutations in conserved elements.
- Primate-specific elements active during fetal development and in specific neuron/glia types are linked to human trait heritability.
Conclusions:
- Regulatory elements play a significant role in the genetic architecture of psychiatric disorders.
- Evolutionary mechanisms shape brain regulatory landscapes, with conserved elements being a primary source of innovation.
- Primate-specific regulatory elements contribute to human brain evolution and heritability of traits.
- The PsychSCREEN platform facilitates access to valuable genetic and epigenetic data for psychiatric disorder research.
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