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Tree Based Co-Clustering Identifies Variation in Chromatin Accessibility Across Hematopoietic Cell Types

Thomas B. George, Nathaniel K. Strawn, Sivan Leviyang
doi: https://doi.org/10.1101/2021.05.07.443145
Thomas B. George
1Department of Mathematics and Statistics, Georgetown University, USA
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Nathaniel K. Strawn
1Department of Mathematics and Statistics, Georgetown University, USA
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Sivan Leviyang
1Department of Mathematics and Statistics, Georgetown University, USA
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  • For correspondence: Sivan.Leviyang@georgetown.edu
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Abstract

Chromatin accessibility, as measured by ATACseq, varies between hematopoietic cell types in different branches of the hematopoietic differentiation tree, e.g. T cells vs B cells, but methods that relate variation in chromatin accessibility to the placement of a cell type on the differentiation tree are lacking. Using an ATACseq dataset recently published by the ImmGen consortium, we construct associations between chromatin accessibility and hematopoietic cell types using a novel co-clustering approach that accounts for the structure of the hematopoietic, differentiation tree. Under a model in which all loci and cell types within a co-cluster have a shared accessibility state, we show that roughly 80% of cell type associated accessibility variation can be captured through 12 cell type clusters and 20 genomic locus clusters. Using publicly available ChIPseq datasets, we show that our clustering reflects transcription factor binding patterns with implications for regulation across cell types. Our results provide a framework for analysis of chromatin state variation across cell types related by a tree or network.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 08, 2021.
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Tree Based Co-Clustering Identifies Variation in Chromatin Accessibility Across Hematopoietic Cell Types
Thomas B. George, Nathaniel K. Strawn, Sivan Leviyang
bioRxiv 2021.05.07.443145; doi: https://doi.org/10.1101/2021.05.07.443145
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Tree Based Co-Clustering Identifies Variation in Chromatin Accessibility Across Hematopoietic Cell Types
Thomas B. George, Nathaniel K. Strawn, Sivan Leviyang
bioRxiv 2021.05.07.443145; doi: https://doi.org/10.1101/2021.05.07.443145

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