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Capturing cell type-specific chromatin structural patterns by applying topic modeling to single-cell Hi-C data

Hyeon-Jin Kim, Galip Gurkan Yardimici, Giancarlo Bonora, Vijay Ramani, Jie Liu, Ruolan Qiu, Choli Lee, Jennifer Hesson, Carol B. Ware, Jay Shendure, Zhijun Duan, William Stafford Noble
doi: https://doi.org/10.1101/534800
Hyeon-Jin Kim
University of Washington;
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Galip Gurkan Yardimici
University of Washington;
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Giancarlo Bonora
University of Washington;
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Vijay Ramani
University of California San Francisco;
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Jie Liu
University of Michigan
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Ruolan Qiu
University of Washington;
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Choli Lee
University of Washington;
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Jennifer Hesson
University of Washington;
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Carol B. Ware
University of Washington;
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Jay Shendure
University of Washington;
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Zhijun Duan
University of Washington;
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William Stafford Noble
University of Washington;
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  • For correspondence: william-noble@uw.edu
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Abstract

Single-cell Hi-C (scHi-C) interrogates genome-wide chromatin interaction in individual cells, allowing us to gain insights into 3D genome organization. However, the extremely sparse nature of scHi-C data poses a significant barrier to analysis, limiting our ability to tease out hidden biological information. In this work, we approach this problem by applying topic modeling to scHi-C data. Topic modeling is well-suited for discovering latent topics in a collection of discrete data. For our analysis, we generate twelve different single-cell combinatorial indexed Hi-C (sciHi-C) libraries from five human cell lines (GM12878, H1Esc, HFF, IMR90, and HAP1), consisting over 25,000 cells. We demonstrate that topic modeling is able to successfully capture cell type differences from sciHi-C data in the form of "chromatin topics." We further show enrichment of particular compartment structures associated with locus pairs in these topics.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 30, 2019.
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Capturing cell type-specific chromatin structural patterns by applying topic modeling to single-cell Hi-C data
Hyeon-Jin Kim, Galip Gurkan Yardimici, Giancarlo Bonora, Vijay Ramani, Jie Liu, Ruolan Qiu, Choli Lee, Jennifer Hesson, Carol B. Ware, Jay Shendure, Zhijun Duan, William Stafford Noble
bioRxiv 534800; doi: https://doi.org/10.1101/534800
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Capturing cell type-specific chromatin structural patterns by applying topic modeling to single-cell Hi-C data
Hyeon-Jin Kim, Galip Gurkan Yardimici, Giancarlo Bonora, Vijay Ramani, Jie Liu, Ruolan Qiu, Choli Lee, Jennifer Hesson, Carol B. Ware, Jay Shendure, Zhijun Duan, William Stafford Noble
bioRxiv 534800; doi: https://doi.org/10.1101/534800

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