# Direct Determination of Multiple Specific Forms of DNA Chemical Modifications in Human Genome

> **NIH NIH R56** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $233,456

## Abstract

PROJECT SUMMARY/ABSTRACT
The information content of DNA is not limited to the primary sequence (A, C, G, T), but is also conveyed by
chemical modifications of individual bases. For example, DNA methylation, specifically 5-methylcytosine (5mC),
has been widely studied for its important regulatory roles in human development and diseases. In addition, the
discovery of active demethylation of 5mC, mediated by TET enzymes, into 5-hydroxymethylcytosine (5hmC),
5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) revealed great insights into the dynamic nature of the
human methylome and its close relevance to multiple human diseases. Beyond these chemical modifications
to cytosine, recent studies by us and others discovered that N6-methyladenine (6mA), another form of
methylation previously thought exclusively existing in bacteria and protozoa, also exists in eukaryotic genomes
including the human genome. In addition to these epigenetic marks, different forms of DNA damages represent
another category of DNA chemical modifications that are of important biological relevance. Although a few
methods for mapping individual chemical modifications have been developed and some are widely used, it is
usually hard for broad researchers to master every protocol to map each form of modification. While third-
generation sequencing technologies support the direct detection of DNA modifications, they face fundamental
challenges distinguishing among different forms of modifications. The objective of this project is to develop a
novel technology for the direct mapping of multiple forms of DNA methylation and DNA damage events
simultaneously. The core idea is that each form of nucleic acid modification has a unique signature in terms of
their physical interaction with DNA polymerase, or nanopores in third-generation sequencing; and these
signatures can be modeled by deep learning methods. We will develop this technology using multiple
innovative strategies to address a few fundamental challenges, and then comprehensively evaluate the
technology to facilitate broad applications.

## Key facts

- **NIH application ID:** 10267380
- **Project number:** 1R56HG011095-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Gang Fang
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $233,456
- **Award type:** 1
- **Project period:** 2020-09-25 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10267380

## Citation

> US National Institutes of Health, RePORTER application 10267380, Direct Determination of Multiple Specific Forms of DNA Chemical Modifications in Human Genome (1R56HG011095-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10267380. Licensed CC0.

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