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 modeling and differentiable programming to propose DEDAL (deep embedding and differentiable alignment), 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 threefold 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.

DeepConsensus improves the accuracy of sequences with a gap-aware sequence transformer.

Circular consensus sequencing with Pacific Biosciences (PacBio) technology generates long (10-25 kilobases), accurate 'HiFi' reads by combining serial observations of a DNA molecule into a consensus sequence. The standard approach to consensus generation, pbccs, uses a hidden Markov model. We introduce DeepConsensus, which uses an alignment-based loss to train a gap-aware transformer-encoder for sequence correction. Compared to pbccs, DeepConsensus reduces read errors 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 4.9 megabases (Mb) to 17.2 Mb), increase gene completeness (94% to 97%), reduce the false gene duplication rate (1.1% to 0.5%), improve assembly base accuracy (Q43 to Q45) and reduce variant-calling errors by 24%. DeepConsensus models could be trained to the general problem of analyzing the alignment of other types of sequences, such as unique molecular identifiers or genome assemblies.

A Unified Software/Hardware Scalable Architecture for Brain-Inspired Computing Based on Self-Organizing Neural Models.

The field of artificial intelligence has significantly advanced over the past decades, inspired by discoveries from the fields of biology and neuroscience. The idea of this work is inspired by the process of self-organization of cortical areas in the human brain from both afferent and lateral/internal connections. In this work, we develop a brain-inspired neural model associating Self-Organizing Maps (SOM) and Hebbian learning in the Reentrant SOM (ReSOM) model. The framework is applied to multimodal classification problems. Compared to existing methods based on unsupervised learning with post-labeling, the model enhances the state-of-the-art results. This work also demonstrates the distributed and scalable nature of the model through both simulation results and hardware execution on a dedicated FPGA-based platform named SCALP (Self-configurable 3D Cellular Adaptive Platform). SCALP boards can be interconnected in a modular way to support the structure of the neural model. Such a unified software and hardware approach enables the processing to be scaled and allows information from several modalities to be merged dynamically. The deployment on hardware boards provides performance results of parallel execution on several devices, with the communication between each board through dedicated serial links. The proposed unified architecture, composed of the ReSOM model and the SCALP hardware platform, demonstrates a significant increase in accuracy thanks to multimodal association, and a good trade-off between latency and power consumption compared to a centralized GPU implementation.