RT Journal Article SR Electronic T1 High-Throughput Single-Molecule Analysis via Divisive Segmentation and Clustering JF bioRxiv FD Cold Spring Harbor Laboratory SP 603761 DO 10.1101/603761 A1 David S. White A1 Marcel P. Goldschen-Ohm A1 Randall H. Goldsmith A1 Baron Chanda YR 2019 UL http://biorxiv.org/content/early/2019/04/09/603761.abstract 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.