# Methods for inferring and analyzing gene regulatory networks using single-cell multiomics and spatial genomics data

> **NIH NIH R35** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $406,218

## Abstract

Project Summary/Abstract
The study of gene regulation provides fundamental mechanistic knowledge to decipher the development of com-
plex biological systems and design treatment strategies for diseases by manipulating cell states. Development
of single-cell multimodal and multiomics sequencing technologies allows for proﬁling of additional epigenomics
information, such as cis-regulatory elements, which enables inference of gene regulation beyond simply gene
coexpression. However, to more accurately identify gene regulation, computational methods are urgently needed
to incorporate both transcriptomics and epigenomics data measured in the same cell. Recent studies show that
epigenomics changes may foreshadow gene transcription, indicating that gene regulation is an asynchronous
process. A set of regulators may not inﬂuence the target gene along the whole continuous biological process but
only in a small time window. However, current gene regulatory networks inferred from time series data provide
average regulation across time rather than characterizing regulation dynamics. Also, prior evidence shows that
cell–cell communication and interaction are present in spatially localized cell populations as a form of regular-
ized activity. Further incorporating time-varying developmental trajectories in tissue-spatial landscapes will help
categorize the spatial heterogeneity of gene regulation. However, we still lack computational methods to incor-
porate spatio-temporal trajectories in gene regulation inference. To close these gaps, my research program will
(1) develop computational methods and statistical approaches to infer both static and dynamic gene regulatory
networks, (2) leverage the spatial trajectories inferred from multiomics and spatial transcriptomics data to charac-
terize spatial gene regulation, and (3) develop control strategies for gene regulatory networks to achieve desired
states using multi-sample single-cell multiomics data. My long-term goal is to characterize gene regulation across
multiple samples and in spatially separated tissue regions and identify the minimum set of driver genes to manip-
ulate cell states (e.g., cell types). Building on my previous experience in gene regulatory network inference and
methods development to analyze multi-sample single-cell genomics and epigenomics data, I will develop novel
statistical methods to infer gene regulatory networks using multi-sample single-cell multiomics data and char-
acterize time-lagged activities. I will build on my recent work on single-cell pseudotime analysis and single-cell
spatio-temporal trajectories to infer gene regulation in temporal and spatio-temporal contexts. Further, building
on my theoretical research in network control and methods development in analyzing multi-sample single-cell
omics data, I will develop control strategies for gene regulatory networks to achieve desired cell states or cell de-
velopmental trajectories with a minimum set of driver genes. Finall...

## Key facts

- **NIH application ID:** 10916287
- **Project number:** 5R35GM150887-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Wenpin Hou
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $406,218
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916287

## Citation

> US National Institutes of Health, RePORTER application 10916287, Methods for inferring and analyzing gene regulatory networks using single-cell multiomics and spatial genomics data (5R35GM150887-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10916287. Licensed CC0.

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