A Cosine Similarity-Based Method to Infer Variability of Chromatin Accessibility at the Single-Cell Level

Frontiers in Genetics
Stanley CaiGolnaz Vahedi

Abstract

Cellular identity between generations of developing cells is propagated through the epigenome particularly via the accessible parts of the chromatin. It is now possible to measure chromatin accessibility at single-cell resolution using single-cell assay for transposase accessible chromatin (scATAC-seq), which can reveal the regulatory variation behind the phenotypic variation. However, single-cell chromatin accessibility data are sparse, binary, and high dimensional, leading to unique computational challenges. To overcome these difficulties, we developed PRISM, a computational workflow that quantifies cell-to-cell chromatin accessibility variation while controlling for technical biases. PRISM is a novel multidimensional scaling-based method using angular cosine distance metrics coupled with distance from the spatial centroid. PRISM takes differences in accessibility at each genomic region between single cells into account. Using data generated in our lab and publicly available, we showed that PRISM outperforms an existing algorithm, which relies on the aggregate of signal across a set of genomic regions. PRISM showed robustness to noise in cells with low coverage for measuring chromatin accessibility. Our approach revealed the ...Continue Reading

References

Oct 30, 2008·Cell·Arjun Raj, Alexander van Oudenaarden
Feb 19, 2010·Nature·Arjun RajAlexander van Oudenaarden
Nov 28, 2012·Cell·Golnaz VahediJohn J O'Shea
Jan 22, 2013·Cell·Renato OstuniGioacchino Natoli
Jun 18, 2015·Nature·Jason D BuenrostroWilliam J Greenleaf
Jan 20, 2017·Nature·Amos Tanay, Aviv Regev
Jun 6, 2017·Nature Reviews. Immunology·Silvia Monticelli, Gioacchino Natoli
Mar 15, 2018·Nature·Darren A CusanovichEileen E M Furlong

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Citations

Mar 4, 2020·Medical & Biological Engineering & Computing·Ling MaBaowei Fei
Jul 6, 2020·Genome Biology·Zhicheng JiHongkai Ji
Feb 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wenliang WangGolnaz Vahedi
Jul 31, 2020·Computational and Structural Biotechnology Journal·Michal T SewerynQin Ma
Feb 14, 2021·Genomics, Proteomics & Bioinformatics·Sarthak SinhaJeff A Biernaskie
Feb 10, 2021·Current Osteoporosis Reports·Muhammad Farooq RaiJennifer J Westendorf
Apr 6, 2021·Computational and Structural Biotechnology Journal·Sally Esmail, Wayne R Danter

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Datasets Mentioned

BETA
GSE99159

Methods Mentioned

BETA
ChIP-seq

Software Mentioned

PRISM
chromVAR
R package
R
ENCODE

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