This enables detection of somatic mutations regardless of mosaicism, albeit it requires the same total sequencing costs as a hypothetical bulk sequencing method with perfect fidelity due to the need to sequence many single cells. In contrast, in single-cell sequencing, the distribution of read depths is the same for somatic mutations and germline (inherited) heterozygous mutations. A, Fidelity: In bulk sequencing, very low-level mosaic mutations cannot be distinguished from sequencing library and sequencing error artifacts. We include a discussion of the fields that will be impacted by single-cell DNA sequencing as the technology continues to advance.ĭNA modifications germ cells lineage tracing organismal development single-cell DNA sequencing single-cell genomics.Ī-C: The three core capabilities of single-cell DNA sequencing (Adapted from ref. Here, we review the applications and biological questions for which single-cell DNA sequencing is uniquely suited or required. 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. Single-cell DNA sequencing also promises significant future biomedical and clinical impact, spanning oncology, fertility, and beyond. 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. Over the past decade, genomic analyses of single cells-the fundamental units of life-have become possible.
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