Chen, C. et al. Science 356, 189–194 (2017).

Demand for single-cell genome sequences is on the rise, especially in areas such as cancer analysis, but whole-genome amplification remains challenging. Chen et al. develop linear amplification via transposon insertion (LIANTI), which uses Tn5 transposition to insert T7 promoters across the genome for in vitro transcription (IVT) followed by cDNA generation, sequencing and digital fragment counting. Amplification by IVT is linear and avoids the exaggerated quantification biases and errors that arise from nonspecific priming and exponential amplification in other protocols. LIANTI provides 97% genome coverage and even amplification, thus enabling accurate detection of copy number variants at 100-kb resolution. In human fibroblasts, the researchers resolve active replication origins and demonstrate low false-positive single-nucleotide-variant detection error. They also characterize UV-induced mutations and trace high C-to-T variant frequencies to cytosine deamination upon cell lysis.