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      SMT Solving for Vesicle Traffic Systems in Cells

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          Abstract

          In biology, there are several questions that translate to combinatorial search. For example, vesicle traffic systems that move cargo within eukaryotic cells have been proposed to exhibit several graph properties such as three connectivity. These properties are consequences of underlying biophysical constraints. A natural question for biologists is: what are the possible networks for various combinations of those properties? In this paper, we present novel SMT based encodings of the properties over vesicle traffic systems and a tool that searches for the networks that satisfies the properties using SMT solvers. In our experiments, we show that our tool can search for networks of sizes that are considered to be relevant by biologists.

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            Defining an essential transcription factor program for naïve pluripotency.

            The gene regulatory circuitry through which pluripotent embryonic stem (ES) cells choose between self-renewal and differentiation appears vast and has yet to be distilled into an executive molecular program. We developed a data-constrained, computational approach to reduce complexity and to derive a set of functionally validated components and interaction combinations sufficient to explain observed ES cell behavior. This minimal set, the simplest version of which comprises only 16 interactions, 12 components, and three inputs, satisfies all prior specifications for self-renewal and furthermore predicts unknown and nonintuitive responses to compound genetic perturbations with an overall accuracy of 70%. We propose that propagation of ES cell identity is not determined by a vast interactome but rather can be explained by a relatively simple process of molecular computation. Copyright © 2014, American Association for the Advancement of Science.
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              Evolution of the eukaryotic membrane-trafficking system: origin, tempo and mode.

              The emergence of an endomembrane system was a crucial stage in the prokaryote-to-eukaryote evolutionary transition. Recent genomic and molecular evolutionary analyses have provided insight into how this critical system arrived at its modern configuration. The apparent relative absence of prokaryotic antecedents for the endomembrane machinery contrasts with the situation for mitochondria, plastids and the nucleus. Overall, the evidence suggests an autogenous origin for the eukaryotic membrane-trafficking machinery. The emerging picture is that early eukaryotic ancestors had a complex endomembrane system, which implies that this cellular system evolved relatively rapidly after the proto-eukaryote diverged away from the other prokaryotic lines. Many of the components of the trafficking system are the result of gene duplications that have produced proteins that have similar functions but differ in their subcellular location. A proto-eukaryote possessing a very simple trafficking system could thus have evolved to near modern complexity in the last common eukaryotic ancestor (LCEA) via paralogous gene family expansion of the proteins encoding organelle identity. The descendents of this common ancestor have undergone further modification of the trafficking machinery; unicellular simplicity and multicellular complexity are the prevailing trend, but there are some remarkable counter-examples.
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                Author and article information

                Journal
                15 April 2018
                Article
                1804.05414
                4556ea64-ddb8-4b0e-8264-785de82d5dcb

                http://creativecommons.org/licenses/by/4.0/

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                Custom metadata
                13 pages, 1 figure, Workshop SASB-2017
                cs.OH

                General computer science
                General computer science

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