Interactive analysis and quality assessment of single-cell copy-number variations

Garvin, Tyler, Aboukhalil, Robert, Kendall, Jude, Baslan, Timour, Atwal, Gurinder S, Hicks, James, Wigler, Michael, Schatz, Michael (2015) Interactive analysis and quality assessment of single-cell copy-number variations. Nature Methods, 12. pp. 1058-1060. ISSN 15487091 (ISSN)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/26344043
DOI: 10.1038/nmeth.3578

Abstract

Single-cell sequencing is emerging as a critical technology for understanding the biology of cancer, neurons, and other complex systems. Here we introduce Ginkgo, a web platform for the interactive analysis and quality assessment of single-cell copy-number alterations. Ginkgo fully automates the process of binning, normalizing, and segmenting mapped reads to infer copy number profiles of individual cells, as well as constructing phylogenetic trees of how those cells are related. We validate Ginkgo by reproducing the results of five major single-cell studies, and discuss how it addresses the wide array of biases that affect single-cell analysis. We also examine the data characteristics of three commonly used single-cell amplification techniques: MDA, MALBAC, and DOP-PCR/WGA4 through comparative analysis of 9 different single-cell datasets. We conclude that DOP-PCR provides the most uniform amplification, while MDA introduces substantial biases into the analysis. Furthermore, given the same level of coverage, our results indicate that data prepared using DOP-PCR can reliably call CNVs at higher resolution than data prepared using either MALBAC or MDA. Ginkgo is freely available at http://qb.cshl.edu/ginkgo.Received November 11, 2014.Accepted November 12, 2014.© 2014, Published by Cold Spring Harbor Laboratory PressThis pre-print is available under a Creative Commons License (Attribution-NonCommercial-NoDerivs 4.0 International), CC BY-NC-ND 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants
Investigative techniques and equipment > assays > Single cell sequencing
CSHL Authors:
Communities: CSHL labs > Atwal lab
CSHL labs > Hicks lab
CSHL labs > Schatz lab
CSHL labs > Wigler lab
School of Biological Sciences > Publications
Depositing User: Matt Covey
Date: 2015
Date Deposited: 22 Jan 2015 21:56
Last Modified: 03 Oct 2019 14:43
PMCID: PMC4775251
Related URLs:
URI: https://repository.cshl.edu/id/eprint/31141

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