A framework for group-wise summarization and comparison of chromatin state annotations

Author:

Vu Ha12ORCID,Koch Zane2,Fiziev Petko123,Ernst Jason1245678ORCID

Affiliation:

1. Bioinformatics Interdepartmental Program, University of California, Los Angeles , Los Angeles, CA 90095, USA

2. Department of Biological Chemistry, University of California, Los Angeles , Los Angeles, CA 90095, USA

3. Illumina Artificial Intelligence Laboratory, Illumina Inc. , Foster City, CA 94404, USA

4. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles , Los Angeles, CA 90095, USA

5. Computer Science Department, University of California, Los Angeles , Los Angeles, CA 90095, USA

6. Jonsson Comprehensive Cancer Center, University of California, Los Angeles , Los Angeles, CA 90095, USA

7. Molecular Biology Institute, University of California, Los Angeles , Los Angeles, CA 90095, USA

8. Computational Medicine Department, University of California, Los Angeles , Los Angeles, CA 90095, USA

Abstract

Abstract Motivation Genome-wide maps of epigenetic modifications are powerful resources for non-coding genome annotation. Maps of multiple epigenetics marks have been integrated into cell or tissue type-specific chromatin state annotations for many cell or tissue types. With the increasing availability of multiple chromatin state maps for biologically similar samples, there is a need for methods that can effectively summarize the information about chromatin state annotations within groups of samples and identify differences across groups of samples at a high resolution. Results We developed CSREP, which takes as input chromatin state annotations for a group of samples. CSREP then probabilistically estimates the state at each genomic position and derives a representative chromatin state map for the group. CSREP uses an ensemble of multi-class logistic regression classifiers that predict the chromatin state assignment of each sample given the state maps from all other samples. The difference in CSREP’s probability assignments for the two groups can be used to identify genomic locations with differential chromatin state assignments. Using groups of chromatin state maps of a diverse set of cell and tissue types, we demonstrate the advantages of using CSREP to summarize chromatin state maps and identify biologically relevant differences between groups at a high resolution. Availability and implementation The CSREP source code and generated data are available at http://github.com/ernstlab/csrep. Supplementary information Supplementary data are available at Bioinformatics online.

Funder

National Institutes of Health

National Science Foundation

Rose Hills Innovator Award

UCLA Jonsson Comprehensive Cancer Center and Eli and Edythe Broad Center of Regenerative Medicine

Stem Cell Research Ablon Scholars Program

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

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