page_title: LIANTI
section_title: 1. Accurate detection of single-cell copy-number variations (CNVs) with kilobase resolution
hierarchical_section_title: LIANTI / Advantages / 1. Accurate detection of single-cell copy-number variations (CNVs) with kilobase resolution
caption_attribution_description: English: Uniformity modified
context_page_description: Linear Amplification via Transposon Insertion is a linear whole genome amplification method. To analyze or sequence very small amount of DNA, i.e. genomic DNA from a single cell, the picograms of DNA is subject to WGA to amplify at least thousands of times into nanogram scale, before DNA analysis or sequencing can be carried out. Previous WGA methods use exponential/nonlinear amplification schemes, leading to bias accumulation and error propagation. LIANTI achieved linear amplification of the whole genome for the first time, enabling more uniform and accurate amplification.
  Shown in the figure is a simulation to illustrate the advantages of linear amplification over exponential amplification, assuming two DNA fragments A and B with replication yields of 100% and 70% per round, respectively. First, linear amplification is more even than exponential amplification. To achieve ~10,000 fold amplification of fragment A, exponential amplification results in a ratio of 8:1, hampering the accuracy of CNV detection. In contrast, linear amplification exhibits a ratio of 1:0.7, which is much closer to unity. Second, linear amplification is superior to exponential amplification in fidelity.
context_section_description: LIANTI exhibits the highest amplification uniformity compared to other single-cell WGA methods, as shown by read depth plots across the genome, as well as coefficient of variation for read depths along the genome as a function of bin size. Together with its unique capability of digital counting to infer fragment numbers based on the mapping coordinates of each amplicon, LIANTI allows accurate detection of single-cell micro-CNVs with kilobase resolution. For comparison, other single-cell WGA methods including DOP-PCR, MDA and MALBAC can only detect CNVs with megabase resolution due to amplification noise, thus completely missing micro-CNVs in single cells.
caption: LIANTI amplification uniformity by read depth plots across the genome
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