TY - JOUR
T1 - Template-based mapping of dynamic motifs in tissue morphogenesis
AU - Stern, Tomer
AU - Shvartsman, Stanislav Y.
AU - Wieschaus, Eric F.
N1 - Funding Information:
TS is supported by the European Molecular Biology Organization Long-Term Fellowship ALTF 215-2017. SYS is supported by the MCB 1516970 award from the NSF. EFW is supported by funding from the Howard Hughes Medical Institute. This research was supported in part by the National Science Foundation under Grant No. NSF PHY-1748958. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to Berthe Y. Choueiry and Shant Karakashian (University of Nebraska-Lincoln) and Stephen G. Hartke (University of Colorado, Denver) for providing the code for ConSubg, to Matej Krajnc (Princeton University, now at Jo?ef Stefan Institute) for sharing insights about junction kinetics and for providing vertex model simulations, to Nareg J.-V. Djabrayan for providing live image of nuclear divisions, to Celia Smits, Jasmin Imran Alsous, David Den-berg, and Rocky Diegmiller for comments on the manuscript, to Trudi Sch?pbach (Princeton University), Elazar Zelzer, Benny Shilo and Eyal Schechter (Weizmann Institute, Israel) for fruitful discussions on tissue organization, to Yosi Keller (Bar-Ilan university, Israel) for consulting on sequence analysis, to Matthew Cahn for technical support in computing resources, to Gary Laevsky for technical support in microscopy imaging, to Reba Samantha, Laisa Eimont and Stephanie Seabrook for bureaucratic assistance and to Heping Jiang for stock maintenance.
Publisher Copyright:
© 2020 Stern et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pcbi.1008049
DO - 10.1371/journal.pcbi.1008049
M3 - Article
C2 - 32822341
AN - SCOPUS:85089802741
SN - 1553-734X
VL - 16
JO - PLoS computational biology
JF - PLoS computational biology
IS - 8 August
M1 - e1008049
ER -