# Computational Methods for Next-Generation Comparative Genomics

> **NIH NIH R01** · CARNEGIE-MELLON UNIVERSITY · 2022 · $354,305

## Abstract

PROJECT SUMMARY
Recent advances in regulatory genomics, especially 3D genome organization in cell nucleus, suggest that
existing methods for cross-species comparisons are limited in their ability to fully understand the evolution of
non-coding genome function. In particular, it is known that genomes are compartmentalized to distinct
compartments in the nucleus such as nuclear lamina and nuclear speckles. Such nuclear
compartmentalization is an essential feature of higher-order genome organization and is linked to various
important genome functions such as DNA replication timing and transcription. Unfortunately, to date no study
exists that directly compares nuclear compartmentalization between human and other mammals. In addition,
there are no computational models available that consider the continuous nature of multiple features of nuclear
compartmentalization and function, which is critical to integrate genome-wide functional genomic data and
datasets that measure cytological distance to multiple compartments across species. In this project, we will
develop novel algorithms and generate new datasets to directly address two key questions: (1) How to identify
the evolutionary patterns of nuclear compartmentalization? (2) What types of sequence evolution may drive
spatial localization changes across species? The proposed project represents the first endeavor in
comparative genomics for nuclear compartmentalization. Our Specific Aims are: (1) Developing new
probabilistic models for identifying evolutionary patterns of nuclear compartmentalization. (2) Identifying
genome-wide evolutionary patterns of nuclear compartmentalization in primate species based on TSA-seq and
Repli-seq. (3) Developing new algorithms to connect sequence features to nuclear compartmentalization
through cross-species comparisons. Successful completion of these aims will result in novel computational
tools and new datasets that will be highly valuable for the comparative genomics community. Integrating the
new computational tools and unique datasets will provide invaluable insights into the relationship between
sequence evolution and changes in nuclear genome organization in mammalian species. Therefore, the
proposed research is expected to advance comparative genomics to a new frontier and provide new
perspectives for studying human genome function

## Key facts

- **NIH application ID:** 10375481
- **Project number:** 5R01HG007352-08
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** JIAN MA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $354,305
- **Award type:** 5
- **Project period:** 2014-09-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375481

## Citation

> US National Institutes of Health, RePORTER application 10375481, Computational Methods for Next-Generation Comparative Genomics (5R01HG007352-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375481. Licensed CC0.

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