# Integrative Cancer Epigenomic Data Analysis Center (ICE-DAC)

> **NIH NIH U24** · VAN ANDEL RESEARCH INSTITUTE · 2020 · $504,521

## Abstract

PROJECT SUMMARY / ABSTRACT
 The past three decades have witnessed an accumulating body of evidence that epigenetic mechanisms
play an instrumental role in human cancer. Epigenetic alterations can serve as driver events in cancer by
inactivating tumor-suppressor genes. The finding that these silencing events are mutually exclusive with
structural or mutational inactivation of the same gene reinforces the functional significance of epigenetic
silencing. The majority of cases of microsatellite instability in sporadic human tumors can be attributed to
epigenetic silencing of the MLH1 mismatch repair gene. One of the most striking discoveries to emerge from
cancer genome projects has been the previously unappreciated preponderance of somatic mutations in
epigenetic regulators in most types of human cancer. Clearly, epigenetic mechanisms play a key role in human
cancer, and a comprehensive molecular characterization of cancer should include epigenomic profiling. We
propose to create an Integrative Cancer Epigenomic Data Analysis Center (ICE-DAC) to provide specialized
analysis pipelines and expertise as part of the Genome Data Analysis Network (GDAN). We anticipate that
epigenomic data will be provided as bisulfite-based sequence data or as DNA methylation BeadArray data,
and we provide an analysis workflow that can accommodate either. We propose to apply specialized
epigenetic analyses we have developed for both data types in our extensive experience in cancer genome
consortia. In Specific Aim 1, we will develop, improve and implement analytic bioinformatic tools for
epigenomic data analysis, including improvements to analysis tools for processing bisulfite sequence data. We
will continue the development of analysis tools that use DNA methylation data to analyze tumor heterogeneity
and subclonal structure, including the deconstruction of non-malignant cellular composition of the tumor. In
Specific Aim 2, we will provide advanced specialized analysis of cancer epigenomic data generated by the
Genome Characterization Center and/or provided through the Data Processing GDAC. Our automated
workflow will provide timely primary data analysis for AWGs, and can accommodate both sequence-based or
array-based DNA methylation data. This workflow will call differentially methylated regions (DMRs), identify
cancer subtypes through stratified cluster analysis, analyze CpH methylation, and analyze tumor purity and
subclonal heterogeneity. Performing variant analysis from bisulfite sequence data allows us to determine the
impact of non-coding mutations on epigenetic state. In Specific Aim 3, we will integrate epigenomic data with
other genomic, transcriptomic, proteomic, and clinical data to derive biologically and clinically relevant novel
insights. Integration of DNA methylation and RNA-Seq data will be used for epigenetic silencing calls and for
our custom enhancer identification ELMER pipeline, both of which will feed into pathway and network analyses.

## Key facts

- **NIH application ID:** 10005291
- **Project number:** 5U24CA210969-05
- **Recipient organization:** VAN ANDEL RESEARCH INSTITUTE
- **Principal Investigator:** PETER W LAIRD
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,521
- **Award type:** 5
- **Project period:** 2016-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005291

## Citation

> US National Institutes of Health, RePORTER application 10005291, Integrative Cancer Epigenomic Data Analysis Center (ICE-DAC) (5U24CA210969-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10005291. Licensed CC0.

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