Digital-WGS: Automated, highly efficient whole-genome sequencing of single cells by digital microfluidics.
Qingyu RuanWeidong RuanXiaoye LinYang WangFenxiang ZouLeiji ZhouZhi ZhuChaoyong James YangPublished in: Science advances (2020)
Single-cell whole-genome sequencing (WGS) is critical for characterizing dynamic intercellular changes in DNA. Current sample preparation technologies for single-cell WGS are complex, expensive, and suffer from high amplification bias and errors. Here, we describe Digital-WGS, a sample preparation platform that streamlines high-performance single-cell WGS with automatic processing based on digital microfluidics. Using the method, we provide high single-cell capture efficiency for any amount and types of cells by a wetted hydrodynamic structure. The digital control of droplets in a closed hydrophobic interface enables the complete removal of exogenous DNA, sufficient cell lysis, and lossless amplicon recovery, achieving the low coefficient of variation and high coverage at multiple scales. The single-cell genomic variations profiling performs the excellent detection of copy number variants with the smallest bin of 150 kb and single-nucleotide variants with allele dropout rate of 5.2%, holding great promise for broader applications of single-cell genomics.
Keyphrases
- single cell
- copy number
- rna seq
- high throughput
- mitochondrial dna
- highly efficient
- induced apoptosis
- deep learning
- machine learning
- genome wide
- circulating tumor
- nucleic acid
- healthcare
- magnetic resonance imaging
- computed tomography
- cell death
- dna methylation
- magnetic resonance
- gene expression
- high resolution
- cell proliferation
- artificial intelligence
- pi k akt
- drug induced