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

Science. 2017 Apr 14;356(6334):189-194. doi: 10.1126/science.aak9787.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cytosine / chemistry
  • DNA Copy Number Variations
  • DNA Transposable Elements / genetics*
  • Deamination
  • Genome, Human
  • Genomics / methods
  • Humans
  • Mutagenesis, Insertional*
  • Polymerase Chain Reaction / methods*
  • Polymorphism, Single Nucleotide*
  • Replication Origin
  • Sequence Analysis, DNA / methods*
  • Single-Cell Analysis / methods*
  • Thymine / chemistry


  • DNA Transposable Elements
  • Cytosine
  • Thymine