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Sequencing by avidity enables high accuracy with low reagent consumption

by Taylor-Weiner, Hermes , Thompson, Connor J. , Bailey, John , Benitez, Chris B. , Khandan, Omid , Chen, Xiyi , Yu, Hua , Ghorbani, Arash , Nunez, Jesus M. , Tomaney, Austin B. , Rong, Daisong , Boddicker, Andrew M. , Levy, Shawn , Kabu, Shradha , Stinson, Ryan , Robertson, Samantha R. , Moreno, Juan , Kruglyak, Semyon , Guetter, Adriana R. , Lopez, Tyler , Liu, Yu , Blease, Kelly N. , Hsieh, Yun-Ting , Sundseth, Keoni J. , Costello, Ryan , Mandla, Kyle A. , Previte, Michael , Meron, Michael , Fu, Yu-Hsien Hwang , Kincade, Daniel E. , Yu, Yingxian , Kellinger, Matthew W. , LeVieux, Jake A. , Guo, Minghao , Damron, Weston , Byrne, Matthew B. , Li, Yu , Altomare, Andrew , Lajoie, Bryan R. , Bondar, Leo , Charov, Katherine , Owens, Jenna , Goddard, Logan A. , Zhou, Chunhong , Arslan, Sinan , Bui, Chris A. , Purba, Josua B. , Mains, Peter T. , Kim, Michael , Hentschel, Jendrik , Wong, Jennifer C. , Ambroso, Mark R. , Mah, Adeline H. , Tjioe, Marco , Yu, Ming , DeBuono, Nicole , Stone, Michael J. , Zhao, Junhua , Zhao, Da , Garcia, Francisco J. , Berti, Lorenzo , Zhang, Xi , Chen, Steve X. , Calleja-Aguirre, Juan , Faustino, Nikka , Piland, Geoffrey , McKean, Daniel T. , Dennler, Claudia N

in Genomics

2022

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Sequencing by avidity enables high accuracy with low reagent consumption

in Genomics

2022

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Sequencing by avidity enables high accuracy with low reagent consumption

in Genomics

2022

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Paper

Sequencing by avidity enables high accuracy with low reagent consumption

Taylor-Weiner, Hermes,

Thompson, Connor J.,

Bailey, John,

Benitez, Chris B.,

Khandan, Omid,

Chen, Xiyi,

Yu, Hua,

Ghorbani, Arash,

Nunez, Jesus M.,

Tomaney, Austin B.,

Rong, Daisong,

Boddicker, Andrew M.,

Levy, Shawn,

Kabu, Shradha,

Stinson, Ryan,

Robertson, Samantha R.,

Moreno, Juan,

Kruglyak, Semyon,

Guetter, Adriana R.,

Lopez, Tyler,

Liu, Yu,

Blease, Kelly N.,

Hsieh, Yun-Ting,

Sundseth, Keoni J.,

Costello, Ryan,

Mandla, Kyle A.,

Previte, Michael,

Meron, Michael,

Fu, Yu-Hsien Hwang,

Kincade, Daniel E.,

Yu, Yingxian,

Kellinger, Matthew W.,

LeVieux, Jake A.,

Guo, Minghao,

Damron, Weston,

Byrne, Matthew B.,

Li, Yu,

Altomare, Andrew,

Lajoie, Bryan R.,

Bondar, Leo,

Charov, Katherine,

Owens, Jenna,

Goddard, Logan A.,

Zhou, Chunhong,

Arslan, Sinan,

Bui, Chris A.,

Purba, Josua B.,

Mains, Peter T.,

Kim, Michael,

Hentschel, Jendrik,

Wong, Jennifer C.,

Ambroso, Mark R.,

Mah, Adeline H.,

Tjioe, Marco,

Yu, Ming,

DeBuono, Nicole,

Stone, Michael J.,

Zhao, Junhua,

Zhao, Da,

Garcia, Francisco J.,

Berti, Lorenzo,

Zhang, Xi,

Chen, Steve X.,

Calleja-Aguirre, Juan,

Faustino, Nikka,

Piland, Geoffrey,

McKean, Daniel T.,

Dennler, Claudia N

2022

Overview

We present avidity sequencing - a novel sequencing chemistry that separately optimizes the process of stepping along a DNA template and the process 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. We demonstrate the use of avidites as a key component of a sequencing technology that surpasses Q40 accuracy and enables a diversity of applications that include single cell RNA-seq and whole human genome sequencing. We also show the advantages of this technology in sequencing through long homopolymers.

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Publisher

Cold Spring Harbor Laboratory

Subject

Genomics