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Destin: toolkit for single-cell analysis of chromatin accessibility

Eugene Urrutia, Li Chen, Haibo Zhou, Yuchao Jiang
doi: https://doi.org/10.1101/461905
Eugene Urrutia
1Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
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Li Chen
2Department of Health Outcomes Research and Policy, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
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Haibo Zhou
1Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
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Yuchao Jiang
1Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
3Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
4Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
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Abstract

Summary Single-cell assay of transposase-accessible chromatin followed by sequencing (scATAC-seq) is an emerging new technology for the study of gene regulation with single-cell resolution. The data from scATAC-seq are unique sparse, binary, and highly variable even within the same cell type. As such, neither methods developed for bulk ATAC-seq nor single-cell RNA-seq data are appropriate. Here, we present Destin, a bioinformatic and statistical framework for comprehensive scATAC-seq data analysis. Destin performs cell-type clustering via weighted principle component analysis, weighting accessible chromatin regions by existing genomic annotations and publicly available regulomic data sets. The weights and additional tuning parameters are determined via model-based likelihood. We evaluated the performance of Destin using downsampled bulk ATAC-seq data of purified samples and scATAC-seq data from seven diverse experiments. Compared to existing methods, Destin was shown to outperform across all data sets and platforms. For demonstration, we further applied Destin to 2,088 adult mouse forebrain cells and identified cell type-specific association of previously reported schizophrenia GWAS loci.

Availability Destin toolkit is freely available as an R package at https://github.com/urrutiag/destin.

Contact yuchaoj{at}email.unc.edu.

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 February 10, 2019.
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Destin: toolkit for single-cell analysis of chromatin accessibility
Eugene Urrutia, Li Chen, Haibo Zhou, Yuchao Jiang
bioRxiv 461905; doi: https://doi.org/10.1101/461905
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Destin: toolkit for single-cell analysis of chromatin accessibility
Eugene Urrutia, Li Chen, Haibo Zhou, Yuchao Jiang
bioRxiv 461905; doi: https://doi.org/10.1101/461905

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