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Biology subjects

Berthet, Q.

Publications and source records attributed to Berthet, Q..

2 recordsLinked to original sources

Deep embedding and alignment of protein sequences

Protein sequence alignment is a key component of most bioinformatics pipelines to study the structures and functions of proteins. Aligning highly divergent sequences remains, however, a difficult task that current algorithms often fail to perform accurately, leaving many proteins or open reading frames poorly annotated. Here, we leverage recent advances in deep learning for language modelling and differentiable programming to propose DEDAL, a flexible model to align protein sequences and detect homologs. DEDAL is a machine learning-based model that learns to align sequences by observing large datasets of raw protein sequences and of correct alignments. Once trained, we show that DEDAL improves by up to two- or three-fold the alignment correctness over existing methods on remote homologs, and better discriminates remote homologs from evolutionarily unrelated sequences, paving the way to improvements on many downstream tasks relying on sequence alignment in structural and functional genomics.

bioinformatics↗

DeepConsensus: Gap-Aware Sequence Transformers for Sequence Correction

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%.

bioinformatics↗