A ML Framework for Genetic Sequence Identification using 2D Electrical Conductance Probability Distributions from Mixed Data Sets

Genetic sequence identification from electrical characterization of single molecules has emerged as a promising alternative to traditional approaches. Since electrical data on single molecules is extremely noisy due to the limitations of even state-of-the-art approaches, achieving high detection rates is challenging, particularly when the task involves being able to distinguish a sequence from its single base-pair mismatches. To address this issue, we propose an architecture based on combining a convolutional neural network with an ensemble learning method, XGBoost. In addition, four different input feature representations are considered, 1D conductance probability distributions and 2D conductance versus distance probability distributions which can be viewed as images, with or without averaging over the experimental parameters. The with averaging case corresponds to feature matrices derived from mixed datasets. We find that 2D probability distributions are helpful with respect to classifier accuracy, but averaged conductance probability distributions are much more impactful and significantly enhance prediction accuracy. Our quantitative analysis of multiple sequences shows an impressive performance increase of approximately 10% for all sequences. While the basis of our analysis is conductance data of DNA strands for COVID-19 Alpha, Beta, and Delta variants and their single base-pair mismatches, our method is generally applicable to other single-molecule identification based on their conductance.