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Digital-WGS: Automated, highly efficient whole-genome sequencing of single cells by digital microfluidics


Abstract
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 dropo ....

National Center , National Natural Science Foundation Of China , Innovative Research Team Of High , Program For Changjiang Scholars , Innovative Research Team In University , Leica Microsystems Inc , Library Prep Kit For Illumina Annoroad , Cell Library Of Chinese Academy Sciences , National Key Rd Program Of China , Phase Flow , Level Set , Intel Xeon , Cell Library , Chinese Academy , Single Cell Master , Single Cell Kit , Thermo Fisher Scientific , Prep Kit , Illumina Hiseq , Biotechnology Information , Hidden Markov , Creative Commons Attribution Noncommercial , National Natural Science Foundation , National Key Rd Program , Innovative Research Team , High Level Local Universities ,