Discovery of DNA–Carbon Nanotube Sensors for Serotonin with Machine Learning and Near-infrared Fluorescence Spectroscopy

DNA-wrapped single walled carbon nanotube (SWNT) conjugates have distinct optical properties leading to their use in biosensing and imaging applications. A critical limitation in the development of DNA-SWNT sensors is the current inability to predict unique DNA sequences that confer a strong analyte-specific optical response to these sensors. Here, near-infrared (nIR) fluorescence response data sets for ∼100 DNA-SWNT conjugates, narrowed down by a selective evolution protocol starting from a pool of ∼10sup10/supunique DNA-SWNT candidates, are used to train machine learning (ML) models to predict DNA sequences with strong optical response to neurotransmitter serotonin. First, classifier models based on convolutional neural networks (CNN) are trained on sequence features to classify DNA ligands as either high response or low response to serotonin. Second, support vector machine (SVM) regression models are trained to predict relative optical response values for DNA sequences. Finally, we demonstrate with validation experiments that integrating the predictions of ensembles of the highest quality neural network classifiers (convolutional or artificial) and SVM regression models leads to the best predictions of both high and low response sequences. With our ML approaches, we discovered five DNA-SWNT sensors with higher fluorescence intensity response to serotonin than obtained previously. Overall, the explored ML approaches, shown to predict useful DNA sequences, can be used for discovery of DNA-based sensors and nanobiotechnologies.