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Integrative Cancer Epigenomic Data Analysis Center (ICE-DAC)

综合癌症表观基因组数据分析中心（ICE-DAC）

基本信息

批准号：
10684894
负责人：
PETER W LAIRD
金额：
$ 44.69万
依托单位：
VAN ANDEL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10684894
关键词：
ATAC-seq Age Attention Base Sequence Binding Sites Biological Assay Cancer Biology Cancer Center Cancer Detection Cancer Model Categories Cells ChIP-seq Chemoresistance Chromatin Clinical Clinical Data Clinical Trials Cluster Analysis Code Competence Complement Custom Cytosine DNA DNA Integration DNA Methylation DNA Modification Process DNA Sequence Alteration Data Data Analyses Defect Development Enhancers Epigenetic Process Event Evolution Formalin Functional disorder Gastrointestinal Neoplasms Genes Genome Genome Data Analysis Network Genomics Growth Higher Order Chromatin Structure Human Hypermethylation MLH1 gene Malignant Neoplasms Malignant neoplasm of gastrointestinal tract Methylation Microsatellite Instability Mismatch Repair Mitosis Molecular Mutation Nature Oncogene Activation Outcome Paraffin Embedding Pathway Analysis Play Prevalence Productivity Proteins Proteomics Quality Control Race Reader Recurrent Malignant Neoplasm Role Sampling Somatic Mutation Specimen Tumor Suppressor Genes Validation Variant bioinformatics tool bisulfite bisulfite sequencing cancer cell cancer classification cancer genome cancer genomics cancer recurrence cancer subtypes chromatin remodeling clinical trial analysis clinically relevant data harmonization determinants of treatment resistance driver mutation epigenetic silencing epigenomic profiling epigenomics exceptional responders gene repair genetic information histone methylation histone modification innovation insight interest molecular pathology mouse model multiple data types novel programs promoter sample fixation sex temporal measurement tool transcription factor transcriptome sequencing transcriptomics tumor

项目摘要

PROJECT SUMMARY / ABSTRACT The widespread nature of epigenetic abnormalities in human cancers has become increasingly appreciated in the past decade, with clinical impacts in cancer detection, cancer classification, chemoresistance prediction, and therapy. Large-scale cancer genomic screens have revealed a previously unrecognized prevalence of somatic mutations among epigenetic regulators in human cancers, including chromatin remodelers, as well as histone or DNA methylation readers, writers, and erasers. 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. Clearly, epigenetic mechanisms play a key role in human cancer, and a comprehensive molecular characterization of cancer should include epigenomic profiling. In 2015 we established an Integrative Cancer Epigenomic Data Analysis Center (ICE-DAC) to provide specialized expertise in epigenomic data analysis as part of the Genome Data Analysis Network (GDAN). We have made major contributions to the GDAN in the past five years, developing cutting-edge DNA methylation bioinformatics tools, leading analysis teams in PanCanAtlas, ATAC-Seq, Pan-Gastrointestinal (Pan-GI) Cancers and Tumor Molecular Pathology (TMP), and making major contributions to the Exceptional Responders (ER) study, testicular germcell tumors (TGCT), data harmonization (QC), CCG Ancestry Informative Markers (AIM), and many other projects. Here we propose to sustain this productive activity in a continuation of the ICE-DAC, lending our deep expertise in epigenomic data analysis to collaborative, integrative genomic and epigenomic analyses of clinical specimens within the NCI GDAN. In Specific Aim 1, we will provide advanced specialized analysis of bulk and single-cell cancer epigenomic data generated by programs within the NCI Center for Cancer Genomics. We have developed various tools for epigenetic analysis and implemented an automated workflow to provide timely primary data analysis for AWGs. In Specific Aim 2 we will implement innovative tools to extract additional information from specialized data types. This Aim maximizes the utility of the data generated, and adds to the rigor of analysis by providing orthogonal validation. These analyses will include prediction of common covariates (such as sex, age and race) for the samples, analysis of tumor purity and composition, inferences of genetic information (including genetic mutation, copy number and large structural variants), all from the DNA methylation assays. 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. Our deep expertise in specialized epigenomics will address a core competency required in GDAN, and complement other genomic analyses of clinical trial samples.

项目摘要/摘要