NLM IRP Seminar Schedule
UPCOMING SEMINARS
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April 30, 2024 Wenya Rowe
The conformal central charge of the spin-1/2 XX model derived from long-chain asymptotics -
May 2, 2024 OPEN
TBD -
May 7, 2024 OPEN
TBD -
May 9, 2024 Pascal Mutz
TBD -
May 14, 2024 Stanley Liang
TBD
RECENT SEMINARS
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April 25, 2024 Ermin Hodzic
Condition-Aware Cell Type Deconvolution of Bulk Tissues -
April 23, 2024 OPEN
TBD -
April 16, 2024 Jaya Srivastava
Regulatory plasticity of the human genome -
April 11, 2024 Sergey Shmakov
Comprehensive survey of the TnpB RNA-guided nucleases -
April 2, 2024 Yifan Yang
Fairness and Bias in Biomedical AI
Scheduled Seminars on April 16, 2024
Contact NLM_IRP_Seminar_Scheduling@mail.nih.gov with questions about this seminar.
Abstract:
Evolutionary turnover in the cis-regulatory elements (CREs) of the human genome accounts for more than 90% of the phenotypic and disease associated traits. Some CREs undergo higher rates of substitution and if mutated, may be more likely to result in phenotypic changes. Genomic substrates of novel enhancer activity can be repurposed CREs, transposable elements, or neutral sequences leading to de-novo emergence. We used a deep learning model that’s capable of correlating nucleotide changes to differential enhancer activity and found that a large majority of CREs between humans and our next closest relatives, chimpanzees, have evolved by repurposing regulatory activity from other cell types. Our results highlight a set of predisposed elements that are more suited to regulatory innovation due to their sequence composition of transcription factor binding sites (TFBSs). TFBS enrichment analysis suggests that the repurposed elements do not conform to specific transcription programs. I will discuss results of our analysis that leads us to hypothesize that the repurposed CREs may act as redundant enhancers, are inefficiently integrated into the transcriptional circuitry, and buffer the impact of unfavorable mutations to confer regulatory robustness.