Abstract

Scalable, inexpensive, and secure testing for SARS-CoV-2 infection is crucial for control of the novel coronavirus pandemic. Recently developed highly multiplexed sequencing assays (HMSAs) that rely on high-throughput sequencing can, in principle, meet these demands, and present promising alternatives to currently used RT-qPCR-based tests. However, reliable analysis, interpretation, and clinical use of HMSAs requires overcoming several computational, statistical and engineering challenges. Using recently acquired experimental data, we present and validate a computational workflow based on kallisto and bustools, that utilizes robust statistical methods and fast, memory efficient algorithms, to quickly, accurately and reliably process high-throughput sequencing data. We show that our workflow is effective at processing data from all recently proposed SARS-CoV-2 sequencing based diagnostic tests, and is generally applicable to any diagnostic HMSA.

Details

Title
Reliable and accurate diagnostics from highly multiplexed sequencing assays
Author
Sina, Booeshaghi A 1 ; Lubock, Nathan B 2 ; Cooper, Aaron R 2 ; Simpkins, Scott W 2 ; Bloom, Joshua S 3 ; Gehring Jase 4 ; Luebbert, Laura 5 ; Kosuri Sri 2 ; Pachter Lior 6 

 California Institute of Technology, Department of Mechanical Engineering, Pasadena, USA (GRID:grid.20861.3d) (ISNI:0000000107068890) 
 Octant Inc., Emeryville, USA (GRID:grid.20861.3d) 
 Octant Inc., Emeryville, USA (GRID:grid.20861.3d); University of California, Los Angeles, Department of Human Genetics, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
 University of Washington, Department of Genome Sciences, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
 California Institute of Technology, Division of Biology and Biological Engineering, Pasadena, USA (GRID:grid.20861.3d) (ISNI:0000000107068890) 
 California Institute of Technology, Division of Biology and Biological Engineering, Pasadena, USA (GRID:grid.20861.3d) (ISNI:0000000107068890); California Institute of Technology, Department of Computing and Mathematical Sciences, Pasadena, USA (GRID:grid.20861.3d) (ISNI:0000000107068890) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2473210842
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.