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DeepConsensus: Gap-Aware Sequence Transformers for Sequence Correction

View ORCID ProfileGunjan Baid, View ORCID ProfileDaniel E. Cook, View ORCID ProfileKishwar Shafin, View ORCID ProfileTaedong Yun, Felipe Llinares-López, Quentin Berthet, View ORCID ProfileAaron M. Wenger, View ORCID ProfileWilliam J. Rowell, View ORCID ProfileMaria Nattestad, Howard Yang, Alexey Kolesnikov, View ORCID ProfileArmin Töpfer, View ORCID ProfileWaleed Ammar, View ORCID ProfileJean-Philippe Vert, View ORCID ProfileAshish Vaswani, View ORCID ProfileCory Y. McLean, View ORCID ProfilePi-Chuan Chang, View ORCID ProfileAndrew Carroll
doi: https://doi.org/10.1101/2021.08.31.458403
Gunjan Baid
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Daniel E. Cook
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Kishwar Shafin
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Taedong Yun
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Felipe Llinares-López
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Quentin Berthet
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Aaron M. Wenger
2Pacific Biosciences, Menlo Park, CA, USA
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William J. Rowell
2Pacific Biosciences, Menlo Park, CA, USA
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Maria Nattestad
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Howard Yang
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Alexey Kolesnikov
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Armin Töpfer
2Pacific Biosciences, Menlo Park, CA, USA
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Waleed Ammar
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Jean-Philippe Vert
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Ashish Vaswani
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Cory Y. McLean
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Pi-Chuan Chang
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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Andrew Carroll
1Google LLC, 1600 Amphitheatre Pkwy, Mountain View, CA
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  • For correspondence: awcarroll@google.com
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Abstract

Pacific BioScience (PacBio) circular consensus sequencing (CCS) generates long (10-25 kb), accurate “HiFi” reads by combining serial observations of a DNA molecule into a consensus sequence. The standard approach to consensus generation uses a hidden Markov model (pbccs). Here, we introduce DeepConsensus, which uses a unique alignment-based loss to train a gap-aware transformer-encoder (GATE) for sequence correction. Compared to pbccs, DeepConsensus reduces read errors in the same dataset by 42%. This increases the yield of PacBio HiFi reads at Q20 by 9%, at Q30 by 27%, and at Q40 by 90%. With two SMRT Cells of HG003, reads from DeepConsensus improve hifiasm assembly contiguity (NG50 4.9Mb to 17.2Mb), increase gene completeness (94% to 97%), reduce false gene duplication rate (1.1% to 0.5%), improve assembly base accuracy (Q43 to Q45), and also reduce variant calling errors by 24%.

Competing Interest Statement

GB, DEC, KS, TY, FLL, QB, MN, HY, AK, WA, JPV, AV, CYM, PCC, and AC are employees of Google LLC and own Alphabet stock as part of the standard compensation package. AMW, AT, and WJR are full-time employees and shareholders of Pacific Biosciences. This study was funded by Google LLC.

Footnotes

  • https://github.com/google/deepconsensus

  • https://console.cloud.google.com/storage/browser/brain-genomics-public/research/deepconsensus/publication

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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DeepConsensus: Gap-Aware Sequence Transformers for Sequence Correction
Gunjan Baid, Daniel E. Cook, Kishwar Shafin, Taedong Yun, Felipe Llinares-López, Quentin Berthet, Aaron M. Wenger, William J. Rowell, Maria Nattestad, Howard Yang, Alexey Kolesnikov, Armin Töpfer, Waleed Ammar, Jean-Philippe Vert, Ashish Vaswani, Cory Y. McLean, Pi-Chuan Chang, Andrew Carroll
bioRxiv 2021.08.31.458403; doi: https://doi.org/10.1101/2021.08.31.458403
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DeepConsensus: Gap-Aware Sequence Transformers for Sequence Correction
Gunjan Baid, Daniel E. Cook, Kishwar Shafin, Taedong Yun, Felipe Llinares-López, Quentin Berthet, Aaron M. Wenger, William J. Rowell, Maria Nattestad, Howard Yang, Alexey Kolesnikov, Armin Töpfer, Waleed Ammar, Jean-Philippe Vert, Ashish Vaswani, Cory Y. McLean, Pi-Chuan Chang, Andrew Carroll
bioRxiv 2021.08.31.458403; doi: https://doi.org/10.1101/2021.08.31.458403

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