Publications by authors named "Gregory Andrews"
Most genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from the PsychENCODE Consortium and other published sources to construct a comprehensive atlas of candidate brain cis-regulatory elements. Using deep learning, we model these elements' sequence syntax and predict how binding sites for lineage-specific transcription factors contribute to cell type-specific gene regulation in various types of glia and neurons.
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- The study investigates the genetic and brain features linked to vocal learning in mammals by comparing data from the Egyptian fruit bat and 215 other placental mammals.* -
- Researchers found that certain proteins evolve more slowly in vocal learners and identified a specific brain region responsible for vocal motor control in the Egyptian fruit bat.* -
- Using machine learning, they uncovered 50 regulatory elements that are associated with vocal learning, suggesting that losses in these elements played a role in the evolution of vocal learning in mammals.*
Article Synopsis
- Thousands of genomic regions related to heritable human diseases have been identified, but understanding their biological significance remains challenging due to unclear functional importance.
- An analysis using single-base phyloP scores from 240 mammals revealed that 3.3% of the human genome is significantly constrained, suggesting these areas are likely functionally important.
- The study found that constrained positions correlate with variants that account for more common disease heritability than other functional annotations, indicating a need for further exploration of the human genome's regulatory landscape in relation to diseases.
Article Synopsis
- Zoonomia is the largest resource for studying mammalian genomes, analyzing 240 species to find genetic mutations that could impact fitness and disease risk.
- Around 332 million bases in the human genome are highly conserved across species, indicating evolutionary significance, with 4552 of these being ultraconserved.
- The research highlights that most constrained bases are outside protein-coding regions and not annotated, revealing potential insights for understanding unique traits in mammals and informing medical research.
Understanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using the reference-free alignment across 241 mammalian genomes produced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.
View Article and Find Full Text PDFAlthough thousands of genomic regions have been associated with heritable human diseases, attempts to elucidate biological mechanisms are impeded by a general inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function that is agnostic to cell type or disease mechanism. Here, single base phyloP scores from the whole genome alignment of 240 placental mammals identified 3.
View Article and Find Full Text PDFThe human genome contains ∼2000 transcriptional regulatory proteins, including ∼1600 DNA-binding transcription factors (TFs) recognizing characteristic sequence motifs to exert regulatory effects on gene expression. The binding specificities of these factors have been profiled both in vitro, using techniques such as HT-SELEX, and in vivo, using techniques including ChIP-seq. We previously developed Factorbook, a TF-centric database of annotations, motifs, and integrative analyses based on ChIP-seq data from Phase II of the ENCODE Project.
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