# Prediction and Validation of Oligodendrocyte Gene Regulatory Network from Multi-Omics

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $400,985

## Abstract

PROJECT ABSTRACT
Studies of several Intellectual/Developmental Disability (IDD) conditions have implicated white
matter alterations in their pathogenesis, and mouse models of oligodendrocyte defects have
validated mechanistic connections with cognitive disorders. In addition, many genetic causes of
leukodystrophies have been identified, including mutations affecting the PLP1 gene in
Pelizaeus-Merzbacher disease. However, due to the lack of tools to interpret significant
variations in the noncoding genome, the ultimate influence of most genetic variants
unfortunately remain uncharacterized. With the resources of PsychEncode and GTEx, a number
of tools have emerged that can be integrated to create a network model of Transcription Factors
(TFs) and their binding sites (TFBS), and several relevant datasets of the oligodendrocyte
epigenome have emerged. The goal of this proposal is to integrate these epigenomic resources
with newly available eQTL resources to develop a model that will improved predictive value in
deciphering Whole Genome Sequencing (WGS) data from patients with a variety of
developmental disabilities related to white matter changes. Along with creating the model, we
will integrate motif analysis of known TFs involved in oligodendrocyte development (MYRF,
SOX10, OLIG2, TCF4 and CHD7/8) to determine if variants alter transcription factor binding
sites (TFBS) in oligodendrocyte-expressed genes. We anticipate that creation an improved
oligodendrocyte GRN will lead to collaborative grant collaborations in several IDD conditions,
such as Autism Spectrum Disorder (ASD), to elucidate the effects of noncoding changes in
WGS and link them to perturbations in the oligodendrocyte network.

## Key facts

- **NIH application ID:** 10509768
- **Project number:** 1R21NS128761-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** John P Svaren
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,985
- **Award type:** 1
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10509768

## Citation

> US National Institutes of Health, RePORTER application 10509768, Prediction and Validation of Oligodendrocyte Gene Regulatory Network from Multi-Omics (1R21NS128761-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10509768. Licensed CC0.

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