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scHiCSRS: A Self-Representation Smoothing Method with Gaussian Mixture Model for Imputing single cell Hi-C Data

Qing Xie, Shili Lin
doi: https://doi.org/10.1101/2021.11.09.467824
Qing Xie
1Interdisciplinary Ph.D. Program in Biostatistics, The Ohio State University, Columbus, OH 43210
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Shili Lin
1Interdisciplinary Ph.D. Program in Biostatistics, The Ohio State University, Columbus, OH 43210
2Department of Statistics, The Ohio State University, Columbus, OH 43210
3Translational Data Analytics Institute, The Ohio State University, Columbus, OH 43210
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  • For correspondence: shili@stat.osu.edu
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Abstract

Motivation Single cell Hi-C techniques make it possible to study cell-to-cell variability in genomic features. However, excess zeros are commonly seen in single cell Hi-C (scHi-C) data, making scHi-C matrices extremely sparse and bringing extra difficulties in downstream analysis. The observed zeros are a combination of two events: structural zeros for which the loci never interact due to underlying biological mechanisms, and dropouts or sampling zeros where the two loci interact but are not captured due to insufficient sequencing depth. Although quality improvement approaches have been proposed as an intermediate step for analyzing scHi-C data, little has been done to address these two types of zeros. We believe that differentiating between structural zeros and dropouts would benefit downstream analysis such as clustering.

Results We propose scHiCSRS, a self-representation smoothing method that improves the data quality, and a Gaussian mixture model that identifies structural zeros among observed zeros. scHiC-SRS not only takes spatial dependencies of a scHi-C 2D data structure into account but also borrows information from similar single cells. Through an extensive set of simulation studies, we demonstrate the ability of scHiCSRS for identifying structural zeros with high sensitivity and for accurate imputation of dropout values in sampling zeros. Downstream analysis for three real datasets show that data improved from scHiCSRS yield more accurate clustering of cells than simply using observed data or improved data from several comparison methods.

Availability and Implementation The scHiCSRS R package, together with the processed real and simulated data used in this study, are available on Github at https://github.com/sl-lin/scHiCSRS.git.

Contact shili{at}stat.osu.edu

Supplementary information Supplementary data are available online.

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-ND 4.0 International license.
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Posted November 11, 2021.
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scHiCSRS: A Self-Representation Smoothing Method with Gaussian Mixture Model for Imputing single cell Hi-C Data
Qing Xie, Shili Lin
bioRxiv 2021.11.09.467824; doi: https://doi.org/10.1101/2021.11.09.467824
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scHiCSRS: A Self-Representation Smoothing Method with Gaussian Mixture Model for Imputing single cell Hi-C Data
Qing Xie, Shili Lin
bioRxiv 2021.11.09.467824; doi: https://doi.org/10.1101/2021.11.09.467824

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