Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI)

• Chongyi ^[1] ; Dong ^[2] ; Longzhi ^[3]
  1. [1] Ten Chen Hospital

     Ten Chen Hospital

     Taoyuan District, Taiwán

     
  2. [2] Xing Wei College

     Xing Wei College

     China

     
  3. [3] Tan

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• Localización: Science, ISSN 0036-8075, Vol. 356, Nº 6334, 2017, págs. 189-194
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.