Applications of Single-Cell DNA Sequencing

Abstract

Over the past decade, genomic analyses of single cells—the fundamental units of life—have become possible. Single-cell DNA sequencing has shed light on biological questions that were previously inaccessible across diverse fields of research, including somatic mutagenesis, organismal development, genome function, and microbiology. Single-cell DNA sequencing also promises significant future biomedical and clinical impact, spanning oncology, fertility, and beyond. While single-cell approaches that profile RNA and protein have greatly expanded our understanding of cellular diversity, many fundamental questions in biology and important biomedical applications require analysis of the DNA of single cells. Here, we review the applications and biological questions for which single-cell DNA sequencing is uniquely suited or required. We include a discussion of the fields that will be impacted by single-cell DNA sequencing as the technology continues to advance. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 22 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Tumor subclones, where are you?

“…Moreover, if there are subclones co-existing within a tumor at similar prevalence, their mutation VAF ranges will inevitably overlap and be difficult to separate. Tumor purity and genomic copy number status will further complicate the condition (Salcedo et al, 2020; Tarabichi et al, 2021), and clonal structure revelation thus calls for single-cell analysis (Davis et al, 2017; Evrony et al, 2021).…”

“…As it is difficult to obtain longitudinal specimens, dissection of clonal evolution is particularly challenging for solid tumors (Bailey et al, 2021). Single-cell profiling of tumor tissues based on somatic mutations will facilitate clonal history reconstruction at unprecedented accuracy, even for samples collected at a single time point (Dong et al, 2017; Evrony et al, 2021; Su et al, 2021). On account of still expensive whole genomic or exonic scale mutational analyses, however, the number of single cells profiled is still limited to hundreds for single-variant resolution studies (Duan et al, 2018; Tang et al, 2021; Wang et al, 2014).…”

A Primer for Single-Cell Sequencing in Non-Model Organisms

“…DNA isolated from a single cell is the target unit for scDNA-seq [ 28 ]. The major technical challenge with scDNA-seq is that sequencing platforms require greater amounts of DNA than an individual cell contains [ 29 ].…”

CellPhy: accurate and fast probabilistic inference of single-cell phylogenies from scDNA-seq data

“…In particular, the reconstruction of cell phylogenies from single-cell DNA sequencing (scDNA-seq) can help us understand the mode and tempo of cell diversification and its mechanisms [ 11 ]. Thus, cell phylogenies can help disentangle key events in the ontogeny of differentiated cell types [ 12 ] and can be used to decipher human development at a remarkable resolution [ 13 – 17 ]. When geographical information is available, cell (and clonal) genealogies can inform us about somatic expansions and cell migrations, which are of great relevance, for example, to understand tumor growth and metastasis [ 18 – 22 ].…”