Cobolt: Integrative Analysis of Multimodal Single-cell Sequencing Data

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2021 Dec 29

PMID 34963480

Citations 56

Authors

Boying Gong

Yun Zhou

Elizabeth Purdom

Affiliations

Soon will be listed here.

Abstract

A growing number of single-cell sequencing platforms enable joint profiling of multiple omics from the same cells. We present Cobolt, a novel method that not only allows for analyzing the data from joint-modality platforms, but provides a coherent framework for the integration of multiple datasets measured on different modalities. We demonstrate its performance on multi-modality data of gene expression and chromatin accessibility and illustrate the integration abilities of Cobolt by jointly analyzing this multi-modality data with single-cell RNA-seq and ATAC-seq datasets.

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References

Gonzalez-Blas C, Minnoye L, Papasokrati D, Aibar S, Hulselmans G, Christiaens V . cisTopic: cis-regulatory topic modeling on single-cell ATAC-seq data. Nat Methods. 2019; 16(5):397-400. PMC: 6517279. DOI: 10.1038/s41592-019-0367-1. View

Franzen O, Gan L, Bjorkegren J . PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford). 2019; 2019. PMC: 6450036. DOI: 10.1093/database/baz046. View

Saelens W, Cannoodt R, Todorov H, Saeys Y . A comparison of single-cell trajectory inference methods. Nat Biotechnol. 2019; 37(5):547-554. DOI: 10.1038/s41587-019-0071-9. View

Qiu X, Hill A, Packer J, Lin D, Ma Y, Trapnell C . Single-cell mRNA quantification and differential analysis with Census. Nat Methods. 2017; 14(3):309-315. PMC: 5330805. DOI: 10.1038/nmeth.4150. View

Hao Y, Hao S, Andersen-Nissen E, Mauck 3rd W, Zheng S, Butler A . Integrated analysis of multimodal single-cell data. Cell. 2021; 184(13):3573-3587.e29. PMC: 8238499. DOI: 10.1016/j.cell.2021.04.048. View

Argelaguet R, Arnol D, Bredikhin D, Deloro Y, Velten B, Marioni J . MOFA+: a statistical framework for comprehensive integration of multi-modal single-cell data. Genome Biol. 2020; 21(1):111. PMC: 7212577. DOI: 10.1186/s13059-020-02015-1. View

Tasic B, Menon V, Nguyen T, Kim T, Jarsky T, Yao Z . Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat Neurosci. 2016; 19(2):335-46. PMC: 4985242. DOI: 10.1038/nn.4216. View

Ding J, Adiconis X, Simmons S, Kowalczyk M, Hession C, Marjanovic N . Systematic comparison of single-cell and single-nucleus RNA-sequencing methods. Nat Biotechnol. 2020; 38(6):737-746. PMC: 7289686. DOI: 10.1038/s41587-020-0465-8. View

Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck 3rd W . Comprehensive Integration of Single-Cell Data. Cell. 2019; 177(7):1888-1902.e21. PMC: 6687398. DOI: 10.1016/j.cell.2019.05.031. View

10.

Sorensen S, Bernard A, Menon V, Royall J, Glattfelder K, Desta T . Correlated gene expression and target specificity demonstrate excitatory projection neuron diversity. Cereb Cortex. 2013; 25(2):433-49. DOI: 10.1093/cercor/bht243. View

11.

Stuart T, Srivastava A, Madad S, Lareau C, Satija R . Single-cell chromatin state analysis with Signac. Nat Methods. 2021; 18(11):1333-1341. PMC: 9255697. DOI: 10.1038/s41592-021-01282-5. View

12.

Risso D, Schwartz K, Sherlock G, Dudoit S . GC-content normalization for RNA-Seq data. BMC Bioinformatics. 2011; 12:480. PMC: 3315510. DOI: 10.1186/1471-2105-12-480. View

13.

Lee J, Hyeon D, Hwang D . Single-cell multiomics: technologies and data analysis methods. Exp Mol Med. 2020; 52(9):1428-1442. PMC: 8080692. DOI: 10.1038/s12276-020-0420-2. View

14.

Neph S, Kuehn M, Reynolds A, Haugen E, Thurman R, Johnson A . BEDOPS: high-performance genomic feature operations. Bioinformatics. 2012; 28(14):1919-20. PMC: 3389768. DOI: 10.1093/bioinformatics/bts277. View

15.

Wu K, Yost K, Chang H, Zou J . BABEL enables cross-modality translation between multiomic profiles at single-cell resolution. Proc Natl Acad Sci U S A. 2021; 118(15). PMC: 8054007. DOI: 10.1073/pnas.2023070118. View

16.

Baker A, Kalmbach B, Morishima M, Kim J, Juavinett A, Li N . Specialized Subpopulations of Deep-Layer Pyramidal Neurons in the Neocortex: Bridging Cellular Properties to Functional Consequences. J Neurosci. 2018; 38(24):5441-5455. PMC: 6001033. DOI: 10.1523/JNEUROSCI.0150-18.2018. View

17.

Stoeckius M, Hafemeister C, Stephenson W, Houck-Loomis B, Chattopadhyay P, Swerdlow H . Simultaneous epitope and transcriptome measurement in single cells. Nat Methods. 2017; 14(9):865-868. PMC: 5669064. DOI: 10.1038/nmeth.4380. View

18.

Cole M, Risso D, Wagner A, DeTomaso D, Ngai J, Purdom E . Performance Assessment and Selection of Normalization Procedures for Single-Cell RNA-Seq. Cell Syst. 2019; 8(4):315-328.e8. PMC: 6544759. DOI: 10.1016/j.cels.2019.03.010. View

19.

Zhu C, Yu M, Huang H, Juric I, Abnousi A, Hu R . An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome. Nat Struct Mol Biol. 2019; 26(11):1063-1070. PMC: 7231560. DOI: 10.1038/s41594-019-0323-x. View

20.

Welch J, Kozareva V, Ferreira A, Vanderburg C, Martin C, Macosko E . Single-Cell Multi-omic Integration Compares and Contrasts Features of Brain Cell Identity. Cell. 2019; 177(7):1873-1887.e17. PMC: 6716797. DOI: 10.1016/j.cell.2019.05.006. View