Template-based mapping of dynamic motifs in tissue morphogenesis. Author Tomer Stern, Stanislav Shvartsman, Eric Wieschaus Publication Year 2020 Type Journal Article Abstract Tissue morphogenesis relies on repeated use of dynamic behaviors at the levels of intracellular structures, individual cells, and cell groups. Rapidly accumulating live imaging datasets make it increasingly important to formalize and automate the task of mapping recurrent dynamic behaviors (motifs), as it is done in speech recognition and other data mining applications. Here, we present a "template-based search" approach for accurate mapping of sub- to multi-cellular morphogenetic motifs using a time series data mining framework. We formulated the task of motif mapping as a subsequence matching problem and solved it using dynamic time warping, while relying on high throughput graph-theoretic algorithms for efficient exploration of the search space. This formulation allows our algorithm to accurately identify the complete duration of each instance and automatically label different stages throughout its progress, such as cell cycle phases during cell division. To illustrate our approach, we mapped cell intercalations during germband extension in the early Drosophila embryo. Our framework enabled statistical analysis of intercalary cell behaviors in wild-type and mutant embryos, comparison of temporal dynamics in contracting and growing junctions in different genotypes, and the identification of a novel mode of iterative cell intercalation. Our formulation of tissue morphogenesis using time series opens new avenues for systematic decomposition of tissue morphogenesis. Keywords Animals, Drosophila, Morphogenesis, Computational Biology, Time Factors, Female, Male, Algorithms, Image Processing, Computer-Assisted, Cell Division, Embryo, Nonmammalian, Microscopy, Confocal, Data Mining Journal PLoS Comput Biol Volume 16 Issue 8 Pages e1008049 Date Published 2020 Aug ISSN Number 1553-7358 DOI 10.1371/journal.pcbi.1008049 Alternate Journal PLoS Comput Biol PMCID PMC7442231 PMID 32822341 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML