PT  - JOURNAL ARTICLE
AU  - Gunjan Baid
AU  - Daniel E. Cook
AU  - Kishwar Shafin
AU  - Taedong Yun
AU  - Felipe Llinares-López
AU  - Quentin Berthet
AU  - Aaron M. Wenger
AU  - William J. Rowell
AU  - Maria Nattestad
AU  - Howard Yang
AU  - Alexey Kolesnikov
AU  - Armin Töpfer
AU  - Waleed Ammar
AU  - Jean-Philippe Vert
AU  - Ashish Vaswani
AU  - Cory Y. McLean
AU  - Pi-Chuan Chang
AU  - Andrew Carroll
TI  - DeepConsensus: Gap-Aware Sequence Transformers for Sequence Correction
AID  - 10.1101/2021.08.31.458403
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.31.458403
4099  - http://biorxiv.org/content/early/2021/08/31/2021.08.31.458403.short
4100  - http://biorxiv.org/content/early/2021/08/31/2021.08.31.458403.full
AB  - 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 StatementGB, 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.