# Dissecting enhancer function through integrative genomics

> **NIH NIH R35** · H. LEE MOFFITT CANCER CTR & RES INST · 2024 · $421,250

## Abstract

PROJECT SUMMARY
Enhancers are non-coding regulatory elements that directly involved in modulating cell-type-specific gene
transcription. Dissecting enhancer function provides critical understanding of human phenotypes and diseases.
Current studies investigate enhancers by profiling one or few of their enhancer features, such as transcription
factor binding, histone modification, chromatin accessibility, non-coding mutation, enhancer transcription and
target gene interaction. To reach a comprehensive evaluation of enhancer function, dynamics, and importance
to human diseases, there is urgent need to jointly analyze enhancer features across human cell types. However,
key barriers exist towards the goal: data heterogeneity, missing enhancer profiles and lack of functional
evaluation consensus. Over the years, we have gained extensive experiences and skills in research areas
including sequence data quality control, machine learning algorithm development as well as enhancer functional
evaluation. The long-term goal of the laboratory is to develop and apply computational methods for analyzing
and interpreting gene regulation in human diseases. Here, we propose to leverage our experiences and skillsets
to develop computational methods in enhancer function dissection through integration of eight different genomic
features from hundreds of human cell types. Specifically, we will focus on three main areas in the next five years
to address the barriers. i) We will develop statistical methods to harmonize heterogeneous data across human
cell types so that sequencing quantification of enhancer features will be comparable and reflect valid enhancer
activities. ii) We will develop machine learning methods to fill the missing enhancer profiles for unmeasured cell
types by learning information from known enhancer profiles, DNA sequences and target gene expression. iii) We
will develop integrative strategies to build enhancer connectome (enhancer-enhancer and enhancer-promoter
interactions) and prioritize cell-type-specific importance of enhancers based on connectome topologies. The
findings from the proposed work will significantly advance our understanding of enhancer function and their
impacts in human diseases.

## Key facts

- **NIH application ID:** 10938828
- **Project number:** 1R35GM155298-01
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** MINGXIANG TENG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $421,250
- **Award type:** 1
- **Project period:** 2024-09-05 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938828

## Citation

> US National Institutes of Health, RePORTER application 10938828, Dissecting enhancer function through integrative genomics (1R35GM155298-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10938828. Licensed CC0.

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