Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI).
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Abstract | Single-cell genomics is important for biology and medicine. However, current whole-genome amplification (WGA) methods are limited by low accuracy of copy-number variation (CNV) detection and low amplification fidelity. Here we report an improved single-cell WGA method, Linear Amplification via Transposon Insertion (LIANTI), which outperforms existing methods, enabling micro-CNV detection with kilobase resolution. This allowed direct observation of stochastic firing of DNA replication origins, which differs from cell to cell. We also show that the predominant cytosine-to-thymine mutations observed in single-cell genomics often arise from the artifact of cytosine deamination upon cell lysis. However, identifying single-nucleotide variations (SNVs) can be accomplished by sequencing kindred cells. We determined the spectrum of SNVs in a single human cell after ultraviolet radiation, revealing their nonrandom genome-wide distribution. |
Year of Publication | 2017
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Journal | Science
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Volume | 356
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Issue | 6334
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Pages | 189-194
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Date Published | 2017 04 14
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ISSN | 1095-9203
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DOI | 10.1126/science.aak9787
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PubMed ID | 28408603
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PubMed Central ID | PMC5538131
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Grant list | DP1 CA186693 / CA / NCI NIH HHS / United States
R33 CA174560 / CA / NCI NIH HHS / United States
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