PT - JOURNAL ARTICLE AU - David S. White AU - Marcel P. Goldschen-Ohm AU - Randall H. Goldsmith AU - Baron Chanda TI - High-Throughput Single-Molecule Analysis via Divisive Segmentation and Clustering AID - 10.1101/603761 DP - 2019 Jan 01 TA - bioRxiv PG - 603761 4099 - http://biorxiv.org/content/early/2019/04/09/603761.short 4100 - http://biorxiv.org/content/early/2019/04/09/603761.full AB - Single-molecule approaches provide insight into the dynamics of biomolecules, yet analysis methods have not scaled with the growing size of data sets acquired in high-throughput experiments. We present a new analysis platform (DISC) that uses divisive clustering to accelerate unsupervised analysis of single-molecule trajectories by up to three orders of magnitude with improved accuracy. Using DISC, we reveal an inherent lack of cooperativity between cyclic nucleotide binding domains from HCN pacemaker ion channels embedded in nanophotonic zero-mode waveguides.