Multi-modal transformer for signal classification in nanopore blockade experiments

Nanopore devices have emerged as powerful tools for single-molecule sensing, with potential for rapid, portable diagnostics. They detect changes in ionic current as analytes enter nanometer-scale pores, providing a means of identifying diverse biomarkers from their characteristic signal patterns. However, these signals are highly complex, and reliably assigning them to specific molecules remains a major challenge. Here, we address this by introducing a multi-modal deep learning architecture that jointly processes multiple signal representations, including raw time-series data, wavelet-based images, and static feature vectors. Our approach surpasses existing methods by more than 10 percentage points on a 42-peptide benchmark and transfers to a 20-amino-acid dataset with near-perfect accuracy. The model integrates complementary information from these representations, with attention analysis showing that the time-series and wavelet-image inputs emphasize different features of the same event. Together, these results demonstrate the potential of machine learning to enable robust, high-accuracy molecular identification with nanopore sensors.

Latent space mapping of interpretable structural coordinates from stochastic single-molecule signals

Nanopores are versatile single-molecular sensors, but their utility is fundamentally constrained by stochastic translocation dynamics warping any encoded information. We resolve it by shifting from time-domain analysis to a learned latent-space mapping via a contrastive encoder trained exclusively on simulated signals from a physics-informed model. This encoder maps solid-state nanopore signals of engineered DNA barcodes into an interpretable molecular coordinate system. The learned representation is responsive to structural barcode parameters while remaining invariant to acquisition conditions and translocation conformation, allowing data pooling across devices. Molecule identification requires a single pass through the encoder, reducing computational cost by three orders of magnitude relative to alignment-based methods. We experimentally validate through mixture quantification, rare-variant detection, consensus barcode reconstruction, and real-time signal acquisition. This shift from temporal analysis to mapping structural coordinates into a latent space changes the paradigm behind analyzing stochastic sensor signals by linking classification to interpretable encoded molecular information.