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Discovering vesicle traffic network constraints by model checking

Shi, Yongtang and Shukla, Ankit and Bhattacharyya, Arnab and Kuppusamy, Lakshmanan and Srivas, Mandayam and Thattai, Mukund (2017) Discovering vesicle traffic network constraints by model checking. In: PLOS ONE, 12 (7). ISSN 1932-6203

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Official URL: https://doi.org/10.1371/journal.pone.0180692

Abstract

A eukaryotic cell contains multiple membrane-bound compartments. Transport vesicles move cargo between these compartments, just as trucks move cargo between warehouses. These processes are regulated by specific molecular interactions, as summarized in the Rothman-Schekman-Sudhof model of vesicle traffic. The whole structure can be represented as a transport graph: each organelle is a node, and each vesicle route is a directed edge. What constraints must such a graph satisfy, if it is to represent a biologically realizable vesicle traffic network? Graph connectedness is an informative feature: 2-connectedness is necessary and sufficient for mass balance, but stronger conditions are required to ensure correct molecular specificity. Here we use Boolean satisfiability (SAT) and model checking as a framework to discover and verify graph constraints. The poor scalability of SAT model checkers often prevents their broad application. By exploiting the special structure of the problem, we scale our model checker to vesicle traffic systems with reasonably large numbers of molecules and compartments. This allows us to test a range of hypotheses about graph connectivity, which can later be proved in full generality by other methods.

Item Type: Journal Article
Publication: PLOS ONE
Publisher: Public Library of Science
Additional Information: The Copyright of this article belongs to the Authors.
Keywords: Biological Transport; Cell Compartmentation; Models, Biological; SNARE Proteins; Transport Vesicles; SNARE protein; cell organelle; model; biological model; cell compartmentalization; metabolism; transport at the cellular level; transport vesicle
Department/Centre: Division of Electrical Sciences > Computer Science & Automation
Date Deposited: 24 Jun 2022 07:29
Last Modified: 24 Jun 2022 07:29
URI: https://eprints.iisc.ac.in/id/eprint/73531

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