@article {Xiao2020.03.16.993584, author = {Minfeng Xiao and Xiaoqing Liu and Jingkai Ji and Min Li and Jiandong Li and Lin Yang and Wanying Sun and Peidi Ren and Guifang Yang and Jincun Zhao and Tianzhu Liang and Huahui Ren and Tian Chen and Huanzi Zhong and Wenchen Song and Yanqun Wang and Ziqing Deng and Yanping Zhao and Zhihua Ou and Daxi Wang and Jielun Cai and Xinyi Cheng and Taiqing Feng and Honglong Wu and Yanping Gong and Huanming Yang and Jian Wang and Xun Xu and Shida Zhu and Fang Chen and Yanyan Zhang and Weijun Chen and Yimin Li and Junhua Li}, title = {Multiple approaches for massively parallel sequencing of HCoV-19 (SARS-CoV-2) genomes directly from clinical samples}, elocation-id = {2020.03.16.993584}, year = {2020}, doi = {10.1101/2020.03.16.993584}, publisher = {Cold Spring Harbor Laboratory}, abstract = {COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.}, URL = {https://www.biorxiv.org/content/early/2020/03/19/2020.03.16.993584}, eprint = {https://www.biorxiv.org/content/early/2020/03/19/2020.03.16.993584.full.pdf}, journal = {bioRxiv} }