# Integrated, cell type specific functional genomics analyses of regulatory sequence elements and their dynamic interaction networks in neuropsychiatric brain tissues

> **NIH NIH U01** · STANFORD UNIVERSITY · 2020 · $1,643,250

## Abstract

Project Summary/Abstract
After a century of debate about the fundamental nature of neuropsychiatric disorders, we know that genetics lie
at their core, yet do not fully understand the critical underlying mechanisms of their disease-causing pathology.
The overall goal of our proposal is the creation of comprehensive and integrated maps of chromatin
accessibility, chromosome folding and transcriptional patterns, delineating regulatory regions in the genomes
of key disease relevant anatomical regions of adult and fetal brains, in brains from patients with Schizophrenia,
Autism Spectrum Disorder, Bipolar Affective Disorder and matched controls, and those with known CNVs
(Copy-Number Variants) that may unmask regional or long-range targets of epigenomic regulatory interactions
that may also be of great relevance in patients with the same clinical phenotype. We will use comprehensive
and highly-resolving epigenomics assays, that were recently developed by us, and novel ways to integrate the
data for the first time in neuropsychiatrically relevant brain tissues. We will generate comprehensive maps of
the spectrum of organization and function of regulatory regions by integrating complementary techniques:
single-cell ATAC-seq (scATAC-seq) to characterize chromatin openness and HiChIP to characterize long-
range folding interactions of sorted neuronal and non-neuronal cells, both of which are coupled to single-cell
RNA-seq and long-range RNA-seq for expression information, further complimented by information about
transcription factors through proteomic analysis of nuclear fractions. These maps will then be combined with
coding or non-coding/regulatory variants in the genomic sequence in the candidate regions and integrated into
the overall PsychENCODE database, which will allow us to create and validate reference maps for epigenomic
marks and interactions, determine aberrations to the reference state in patient tissue, and connect such
aberrations to genetic disease loci as well as assemble such loci into disease pathways. This project will not
only greatly expand our understanding of regulatory information encoded in the human genome and its impact
on human brain development and neuropsychiatric disorders, but also produce the bioinformatics tools
necessary to analyze the complex data being generated in PsychENCODE.

## Key facts

- **NIH application ID:** 9961663
- **Project number:** 5U01MH116529-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JOACHIM F HALLMAYER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,643,250
- **Award type:** 5
- **Project period:** 2019-06-20 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961663

## Citation

> US National Institutes of Health, RePORTER application 9961663, Integrated, cell type specific functional genomics analyses of regulatory sequence elements and their dynamic interaction networks in neuropsychiatric brain tissues (5U01MH116529-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9961663. Licensed CC0.

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