Sully F. Chen

Sully F. Chen, Robert J. Steele, Glen M. Hocky et al.

The transformer architecture has revolutionized bioinformatics and driven progress in the understanding and prediction of the properties of biomolecules. To date, most biosequence transformers have been trained on single-omic data - either proteins or nucleic acids - and have seen incredible success in downstream tasks in each domain, with particularly noteworthy breakthroughs in protein structural modeling. However, single-omic pretraining limits the ability of these models to capture cross-modal interactions. Here we present OmniBioTE, the largest open-source multi-omic model trained on over 250 billion tokens of mixed protein and nucleic acid data. We show that despite only being trained on unlabeled sequence data, OmniBioTE learns joint representations mapping genes to their corresponding protein sequences. We further demonstrate that OmniBioTE achieves state-of-the-art results predicting the change in Gibbs free energy ({ΔG}) of the binding interaction between a given nucleic acid and protein. Remarkably, we show that multi-omic biosequence transformers emergently learn useful structural information without any a priori structural training, allowing us to predict which protein residues are most involved in the protein-nucleic acid binding interaction. Compared to single-omic controls trained with identical compute, OmniBioTE also demonstrates superior performance-per-FLOP across both multi-omic and single-omic benchmarks. Together, these results highlight the power of a unified modeling approach for biological sequences and establish OmniBioTE as a foundation model for multi-omic discovery.

Sully F. Chen, Zhicheng Guo, Cheng Ding et al.

Rapid, reliable, and accurate interpretation of medical time-series signals is crucial for high-stakes clinical decision-making. Deep learning methods offered unprecedented performance in medical signal processing but at a cost: they were compute-intensive and lacked interpretability. We propose Sparse Mixture of Learned Kernels (SMoLK), an interpretable architecture for medical time series processing. SMoLK learns a set of lightweight flexible kernels that form a single-layer sparse neural network, providing not only interpretability, but also efficiency, robustness, and generalization to unseen data distributions. We introduce a parameter reduction techniques to reduce the size of SMoLK's networks while maintaining performance. We test SMoLK on two important tasks common to many consumer wearables: photoplethysmography (PPG) artifact detection and atrial fibrillation detection from single-lead electrocardiograms (ECGs). We find that SMoLK matches the performance of models orders of magnitude larger. It is particularly suited for real-time applications using low-power devices, and its interpretability benefits high-stakes situations.