Conceptual modeling of mRNA decay provokes new hypotheses.

Biologists are required to integrate large amounts of data to construct a working model of the system under investigation. This model is often informal and stored mentally or textually, making it prone to contain undetected inconsistencies, inaccuracies, or even contradictions, not much less than a...

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Autores principales:	Judith Somekh, Gal Haimovich, Adi Guterman, Dov Dori, Mordechai Choder
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f73c1ee18e024cd39c315ae811b5d257
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spelling	oai:doaj.org-article:f73c1ee18e024cd39c315ae811b5d2572021-11-25T05:59:14ZConceptual modeling of mRNA decay provokes new hypotheses.1932-620310.1371/journal.pone.0107085https://doaj.org/article/f73c1ee18e024cd39c315ae811b5d2572014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107085https://doaj.org/toc/1932-6203Biologists are required to integrate large amounts of data to construct a working model of the system under investigation. This model is often informal and stored mentally or textually, making it prone to contain undetected inconsistencies, inaccuracies, or even contradictions, not much less than a representation in free natural language. Using Object-Process Methodology (OPM), a formal yet visual and humanly accessible conceptual modeling language, we have created an executable working model of the mRNA decay process in Saccharomyces cerevisiae, as well as the import of its components to the nucleus following mRNA decay. We show how our model, which incorporates knowledge from 43 articles, can reproduce outcomes that match the experimental findings, evaluate hypotheses, and predict new possible outcomes. Moreover, we were able to analyze the effects of the mRNA decay model perturbations related to gene and interaction deletions, and predict the nuclear import of certain decay factors, which we then verified experimentally. In particular, we verified experimentally the hypothesis that Rpb4p, Lsm1p, and Pan2p remain bound to the RNA 3'-untranslated region during the entire process of the 5' to 3' degradation of the RNA open reading frame. The model has also highlighted erroneous hypotheses that indeed were not in line with the experimental outcomes. Beyond the scientific value of these specific findings, this work demonstrates the value of the conceptual model as an in silico vehicle for hypotheses generation and testing, which can reinforce, and often even replace, risky, costlier wet lab experiments.Judith SomekhGal HaimovichAdi GutermanDov DoriMordechai ChoderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107085 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Judith Somekh Gal Haimovich Adi Guterman Dov Dori Mordechai Choder Conceptual modeling of mRNA decay provokes new hypotheses.
description	Biologists are required to integrate large amounts of data to construct a working model of the system under investigation. This model is often informal and stored mentally or textually, making it prone to contain undetected inconsistencies, inaccuracies, or even contradictions, not much less than a representation in free natural language. Using Object-Process Methodology (OPM), a formal yet visual and humanly accessible conceptual modeling language, we have created an executable working model of the mRNA decay process in Saccharomyces cerevisiae, as well as the import of its components to the nucleus following mRNA decay. We show how our model, which incorporates knowledge from 43 articles, can reproduce outcomes that match the experimental findings, evaluate hypotheses, and predict new possible outcomes. Moreover, we were able to analyze the effects of the mRNA decay model perturbations related to gene and interaction deletions, and predict the nuclear import of certain decay factors, which we then verified experimentally. In particular, we verified experimentally the hypothesis that Rpb4p, Lsm1p, and Pan2p remain bound to the RNA 3'-untranslated region during the entire process of the 5' to 3' degradation of the RNA open reading frame. The model has also highlighted erroneous hypotheses that indeed were not in line with the experimental outcomes. Beyond the scientific value of these specific findings, this work demonstrates the value of the conceptual model as an in silico vehicle for hypotheses generation and testing, which can reinforce, and often even replace, risky, costlier wet lab experiments.
format	article
author	Judith Somekh Gal Haimovich Adi Guterman Dov Dori Mordechai Choder
author_facet	Judith Somekh Gal Haimovich Adi Guterman Dov Dori Mordechai Choder
author_sort	Judith Somekh
title	Conceptual modeling of mRNA decay provokes new hypotheses.
title_short	Conceptual modeling of mRNA decay provokes new hypotheses.
title_full	Conceptual modeling of mRNA decay provokes new hypotheses.
title_fullStr	Conceptual modeling of mRNA decay provokes new hypotheses.
title_full_unstemmed	Conceptual modeling of mRNA decay provokes new hypotheses.
title_sort	conceptual modeling of mrna decay provokes new hypotheses.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f73c1ee18e024cd39c315ae811b5d257
work_keys_str_mv	AT judithsomekh conceptualmodelingofmrnadecayprovokesnewhypotheses AT galhaimovich conceptualmodelingofmrnadecayprovokesnewhypotheses AT adiguterman conceptualmodelingofmrnadecayprovokesnewhypotheses AT dovdori conceptualmodelingofmrnadecayprovokesnewhypotheses AT mordechaichoder conceptualmodelingofmrnadecayprovokesnewhypotheses
_version_	1718414318089797632

Conceptual modeling of mRNA decay provokes new hypotheses.

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