Computational Systems Biology Methods and Protocols.7z

Chapter 19

Applications of Single-Cell Sequencing for Multiomics

Yungang Xu and Xiaobo Zhou

Abstract

Single-cell sequencing interrogates the sequence or chromatin information from individual cells with
advanced next-generation sequencing technologies. It provides a higher resolution of cellular differences
and a better understanding of the underlying genetic and epigenetic mechanisms of an individual cell in the
context of its survival and adaptation to microenvironment. However, it is more challenging to perform
single-cell sequencing and downstream data analysis, owing to the minimal amount of starting materials,
sample loss, and contamination. In addition, due to the picogram level of the amount of nucleic acids used,
heavy amplification is often needed during sample preparation of single-cell sequencing, resulting in the
uneven coverage, noise, and inaccurate quantification of sequencing data. All these unique properties raise
challenges in and thus high demands for computational methods that specifically fit single-cell sequencing
data. We here comprehensively survey the current strategies and challenges for multiple single-cell sequenc-
ing, including single-cell transcriptome, genome, and epigenome, beginning with a brief introduction to
multiple sequencing techniques for single cells.

KeywordsSingle-cell sequencing, Single-cell transcriptome, Genome, Epigenome, Multiomics,

Allele-specific expression, Single nucleotide variant calling, Clonal structure

1 Multiple Sequencing Protocols for Single Cells

Next-generation sequencing (NGS) technologies allow increasing

ability to profile transcriptome [1], genome [2], epigenome [3],

and even protein [4, 5] of single cells sampled from heterogeneous

cell types and different cellular states. Multiple molecular measure-

ments from single cells enable normal development and disease

processes to be studied and dissected at the resolution of individual

cell. In this section, we first review the developments, opportunities,

and challenges of multiple single-cell sequencing technologies,

which have enabled comprehensively understanding and modeling

cellular processes regarding development and diseases. Like conven-

tional NGS experiments, the protocols of a single-cell sequencing

generally contain the following steps: isolation of single cell, nucleic

Tao Huang (ed.),Computational Systems Biology: Methods and Protocols, Methods in Molecular Biology, vol. 1754,
https://doi.org/10.1007/978-1-4939-7717-8_19,©Springer Science+Business Media, LLC, part of Springer Nature 2018

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