In this project, we will develop novel methods for finding brain-specific enhancers, build regulatory networks, deconvolve brain-region-specific regulation, and relate differential enhancer signals to variations in the human population. We will then apply these analytical methods to the psychENCODE data corpus, integrating these data with GTEx, ENCODE, and CommonMind data, annotating GWAS SNPs associated with psych disease, prioritizing the discovered regulatory elements for validation, and visualizing all psychENCODE data in an integrated fashion. We will then validate these predicted regulatory elements using large-scale genomic assays in neuroblastoma cells, iPSC cells, and neuronal precursor cells differentiated into neuronal lineages, and using a microfluidics platform capable of culturing neuronal cells and neuronal organoids. The results from these studies will further our understanding of the genetic regulatory basis for neuronal function in both normal and neuropsychiatric disease states.

Public Health Relevance

The data generated by the psychENCODE Consortium are a pre-eminent, centralized resource for studying the human brain. We will develop cutting-edge analytical methods and apply them to the psychENCODE data corpus to identify regulatory elements and then validate them using large-scale genomic assays in neuronal cells and organoids. Our results will further our understanding of the human brain in the healthy state and neuropsychiatric diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01MH116492-03
Application #
9896859
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Arguello, Alexander
Project Start
2018-07-06
Project End
2023-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Wang, Daifeng; Liu, Shuang; Warrell, Jonathan et al. (2018) Comprehensive functional genomic resource and integrative model for the human brain. Science 362:
PsychENCODE Consortium; Akbarian, Schahram; Liu, Chunyu et al. (2015) The PsychENCODE project. Nat Neurosci 18:1707-12