The 2018/2019 Belleau Lecture: Sunny Xie - Single Cell Genomics: When Stochasticity Meets Precision
Abstract:
DNA exists as single molecules in individual cells. Genomic variations such as copy-number variations (CNVs) and single nucleotide variations (SNVs) in a single cell occur in a stochastic way, necessitating single-cell and single-molecule measurements to be identified. However, existing single-cell whole genome amplification (WGA) methods are limited by low accuracy of CNV and SNV detection. We have developed transposase-based methods for single-cell WGA, which have superseded previous methods.
With the improved genome coverage of our new WGA method, we have also developed a high-resolution single-cell chromatin conformation capture method, which allows for the first 3D genome map of a human diploid cell.
Gene expression is also stochastic due to the fact that the DNA exists as single-molecules in individual cells. The correlations among different mRNAs in a single-cell are masked within the stochastic gene expression noise. We have developed a method for single-cell transcriptome with improved detection efficiency and accuracy, revealing intrinsic correlations among all detected mRNAs in a single-cell. For a particular human cell type, we uncovered ~148 transcriptionally correlated modules (TCMs) from the gene expression data of ~1000 individual cells under a steady state condition. We found that the TCMs are cell type dependent.
Bio:
Professor Xiaoliang Sunney Xie is an internationally renowned biophysical chemist, and the Lee Shao-kee professor of Peking University. After a career at Pacific Northwest National Laboratory, he became the first tenured professor at Harvard University among Chinese scholars who went to the US since the Reform in China. As a pioneer of single-molecule biophysical chemistry, coherent Raman scattering microscopy, and single-cell genomics, he made major contributions to the emergence of these fields. In particular, his inventions in single-cell genomics have been used in in vitro fertilization to benefit hundreds of couples in China by avoiding the transmission of monogenic diseases to their newborns.