Reverse-time inference of biological dynamics

by Nicolas Lenner
Doctoral thesis
Date of Examination:2019-11-13
Date of issue:2020-10-27
Advisor:Prof. Dr. Fred Wolf
Referee:Prof. Dr. Fred Wolf
Referee:Prof. Dr. Jörg Großhans
Referee:Prof. Dr. Jörg Enderlein
Referee:Prof. Dr. Stefan Klumpp
Referee:Prof. Dr. Ulrich Parlitz
Referee:Prof. Dr. Michael Wibral
Persistent Address: http://dx.doi.org/10.53846/goediss-8241

 

 

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Abstract

English

In this work I derive a mathematical theory that allows to infer directional biological dynamics in reverse time starting from their target state. I use this approach to infer an effective model of cell junction shrinkage during cell intercalation mediated germband extension in Drosophila embryogenesis. Due to the intrinsic stochasticity of time dependent biological observables, a single observation is not sufficient to characterize the measured process. Instead, a set of independently recorded sample paths is required to form an ensemble and evaluate its statistics. I suggest analyzing such data sets in their natural frame of reference, i.e. by target state alignment. Target state alignment (TSA) allows to determine whether and at which point such a system can be summarized into a single effective dynamic. Target state alignment however also creates pseudo forces. The TSA theory allows me to separate these spurious forces from the true underlying dynamics. Different from previous work, the TSA theory allows the inference of non-linear, non-equilibrium dynamics irrespective of any possibly unknown initial conditions. Applied to Drosophila germband extension this statistical approach establishes a visco-elastic model of junction shrinkage.
Keywords: reverse-time inference; stochastic dynamics; target state alignment; developmental biology; Drosophila embryogenesis; cell intercalation; germband extension
 
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