Xi Chen (Troyanskaya Lab)
"Tissue-specific enhancer functional networks for associating distal regulatory regions to disease"
Abstract: Understanding disease-associated dysregulation of enhancers has the potential to reveal pathogenic signals, yet systematic study of tissue-specific function of enhancers and their disease associations is a major open challenge. We present an integrative framework, FENRIR, that integrates thousands of transcription factor binding (ChIP-seq) and chromatin interaction experiments (ChIA-PET) with functional networks of genes to infer tissue-specific functional relationships between enhancers for 140 diverse human tissues and cell types. FENRIR provides a novel regulatory-region-centric approach to systematically identify disease-associated enhancers. We focused on the brain-specific network and demonstrated its power to accurately prioritize enhancers associated with several complex neurological diseases, including autism spectrum disorder (ASD), Alzheimer’s disease, Parkinson’s disease and Schizophrenia. Our top prioritized ASD-associated enhancers showed a significant proband-specific de novo mutation enrichment, indicating pathogenic signal. Furthermore, we experimentally validated transcriptional regulatory activities of three enhancers not previously reported with ASD and demonstrated their differential regulatory potential between ASD proband and sibling alleles. Thus, FENRIR is an accurate and effective framework for the study of tissue-specific enhancers and their role in disease. FENRIR can be accessed at fenrir.flatironinstitute.org/.
Pierre Ronceray (Wingreen Lab)
"The unusual properties of high specificity protein liquids"
Abstract: Many intracellular bodies are now understood to behave as phase-separated liquid droplets. Among those, a biologically relevant class of condensates are those for which phase separation is driven by specific one-to-one interactions between complementary proteins. In this talk, I will discuss how the physical properties of such liquids might differ from those of usual molecular liquids, for instance at the level of their phase boundaries, relaxation properties, and surface tension. The mechanisms specific to this class of liquids provide, I will argue, additional knobs that cells could use to finely tune and dynamically adjust the physical properties of their constituents.
Think and Drink will be held on three Wednesdays this Fall semester: 9/25, 10/9, and 11/13 from 4:30-5:30 pm (Spring dates TBD). The format is two 20 minute talks followed by pizza and beer for seminar attendees. If you would like to secure your spot at a Think and Drink seminar, please contact Aleena Patel (firstname.lastname@example.org) or Shawn Davidson (email@example.com).