1. Sequencing by avidity enables high accuracy with low reagent consumption
- Author
-
Sinan Arslan, Francisco J. Garcia, Minghao Guo, Matthew W. Kellinger, Semyon Kruglyak, Jake A. LeVieux, Adeline H. Mah, Haosen Wang, Junhua Zhao, Chunhong Zhou, Andrew Altomare, John Bailey, Matthew B. Byrne, Chiting Chang, Steve X. Chen, Byungrae Cho, Claudia N. Dennler, Vivian T. Dien, Derek Fuller, Ryan Kelley, Omid Khandan, Michael G. Klein, Michael Kim, Bryan R. Lajoie, Bill Lin, Yu Liu, Tyler Lopez, Peter T. Mains, Andrew D. Price, Samantha R. Robertson, Hermes Taylor-Weiner, Ramreddy Tippana, Austin B. Tomaney, Su Zhang, Minna Abtahi, Mark R. Ambroso, Rosita Bajari, Ava M. Bellizzi, Chris B. Benitez, Daniel R. Berard, Lorenzo Berti, Kelly N. Blease, Angela P. Blum, Andrew M. Boddicker, Leo Bondar, Chris Brown, Chris A. Bui, Juan Calleja-Aguirre, Kevin Cappa, Joshua Chan, Victor W. Chang, Katherine Charov, Xiyi Chen, Rodger M. Constandse, Weston Damron, Mariam Dawood, Nicole DeBuono, John D. Dimalanta, Laure Edoli, Keerthana Elango, Nikka Faustino, Chao Feng, Matthew Ferrari, Keith Frankie, Adam Fries, Anne Galloway, Vlad Gavrila, Gregory J. Gemmen, James Ghadiali, Arash Ghorbani, Logan A. Goddard, Adriana Roginski Guetter, Garren L. Hendricks, Jendrik Hentschel, Daniel J. Honigfort, Yun-Ting Hsieh, Yu-Hsien Hwang Fu, Scott K. Im, Chaoyi Jin, Shradha Kabu, Daniel E. Kincade, Shawn Levy, Yu Li, Vincent K. Liang, William H. Light, Jonathan B. Lipsher, Tsung-li Liu, Grace Long, Rui Ma, John M. Mailloux, Kyle A. Mandla, Anyssa R. Martinez, Max Mass, Daniel T. McKean, Michael Meron, Edmund A. Miller, Celyne S. Moh, Rachel K. Moore, Juan Moreno, Jordan M. Neysmith, Cassandra S. Niman, Jesus M. Nunez, Micah T. Ojeda, Sara Espinosa Ortiz, Jenna Owens, Geoffrey Piland, Daniel J. Proctor, Josua B. Purba, Michael Ray, Daisong Rong, Virginia M. Saade, Sanchari Saha, Gustav Santo Tomas, Nicholas Scheidler, Luqmanal H. Sirajudeen, Samantha Snow, Gudrun Stengel, Ryan Stinson, Michael J. Stone, Keoni J. Sundseth, Eileen Thai, Connor J. Thompson, Marco Tjioe, Christy L. Trejo, Greg Trieger, Diane Ni Truong, Ben Tse, Benjamin Voiles, Henry Vuong, Jennifer C. Wong, Chiung-Ting Wu, Hua Yu, Yingxian Yu, Ming Yu, Xi Zhang, Da Zhao, Genhua Zheng, Molly He, and Michael Previte
- Subjects
Biomedical Engineering ,Molecular Medicine ,Bioengineering ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase–polymer–nucleotide complexes bound to clonal copies of DNA targets. These polymer–nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer.
- Published
- 2023
- Full Text
- View/download PDF