w
1118. (
B) Heatmap of the expression of TSC genes averaged across 2 days of observation. The presence of the characteristic circadian patterns in the tissue is indicated with black rectangles around the heatmaps. The number at the left designates the number of detected TSC genes. (
C and
D) Heatmap of cycling in two (C) and three tissues (D) gene expression averaged across 2 days of observation. Black rectangles indicate tissues in which genes were found to be cycling. For (B) to (D), lighter areas or the heatmaps correspond to lower expression levels. The time is indicated at the bottom of the heatmap. (
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
2State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
3National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
4University of Chinese Academy of Sciences, Beijing 100049, China.
5Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University, Beijing 100871, China.
6Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
7Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China.
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 dropout rat