# Computational tools for regulome mapping using single-cell genomic data

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

Project Summary
Understanding how genes' activities are controlled is crucial for elucidating the basic operating rules of biology
and molecular mechanisms of diseases. Recent innovations in single-cell genomic technologies have opened the
door to analyzing a variety of functional genomic features in individual cells. These technologies enable scientists
to systematically discover unknown cell subpopulations in complex tissue and disease samples, and allow them
to reconstruct a sample's gene regulatory landscape at an unprecedented cellular resolution. Despite these
promising developments, many challenges still exist and must be overcome before one can fully decode gene
regulation at the single-cell resolution. In particular, current technologies lack the ability to accurately measure the
activity of each individual cis-regulatory element (CRE) in a single cell. They also cannot measure all functional
genomic data types in the same cell. Moreover, the prevalent technical biases and noises in single-cell genomic
data make computational analysis non-trivial. With rapid growth of data, lack of computational tools for data
analysis has become a rate-limiting factor for effective applications of single-cell genomic technologies.
 The objective of this proposal is to develop computational and statistical methods and software tools for
mapping and analyzing gene regulatory landscape using single-cell genomic data. Our Aim 1 addresses the
challenge of accurately measuring CRE activities in single cells using single-cell regulome data. Regulome,
deﬁned as the activities of all cis-regulatory elements in a genome, contains crucial information for understanding
gene regulation. The state-of-the-art technologies for mapping regulome in a single cell produce sparse data that
cannot accurately measure activities of individual CREs. We will develop a new computational framework to allow
more accurate analysis of individual CREs' activities in single cells using sparse data. Our Aim 2 addresses the
challenge of collecting multiple functional genomic data types in the same cell. We will develop a method that
uses single-cell RNA sequencing (scRNA-seq), the most widely used single-cell functional genomic technology,
to predict cells' regulatory landscape. Since most scRNA-seq datasets do not have accompanying single-cell data
for other -omics data types, our method will also signiﬁcantly expand the utility and increase the value of scRNA-
seq experiments. Our Aim 3 addresses the challenge of integrating different data types generated by different
single-cell genomic technologies from different cells. We will develop a method to align single-cell RNA-seq and
single-cell regulome data to generate an integrated map of transcriptome and regulome.
 Upon completion of this proposal, we will deliver our methods through open-source software tools. These tools
will be widely useful for analyzing and integrating single-cell regulome and transcriptome data. By addressing
sev...

## Key facts

- **NIH application ID:** 10001077
- **Project number:** 5R01HG010889-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Hongkai Ji
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2019-08-22 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001077

## Citation

> US National Institutes of Health, RePORTER application 10001077, Computational tools for regulome mapping using single-cell genomic data (5R01HG010889-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001077. Licensed CC0.

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