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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2014
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| Online Access: | http://hdl.handle.net/1721.1/90997 https://orcid.org/0000-0002-2393-3124 |
| _version_ | 1826197032553938944 |
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| author | Somekh, Judith Haimovich, Gal Guterman, Adi Dori, Dov Choder, Mordechai |
| author2 | Massachusetts Institute of Technology. Engineering Systems Division |
| author_facet | Massachusetts Institute of Technology. Engineering Systems Division Somekh, Judith Haimovich, Gal Guterman, Adi Dori, Dov Choder, Mordechai |
| author_sort | Somekh, Judith |
| collection | MIT |
| 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′-untralslated 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. |
| first_indexed | 2024-09-23T10:41:22Z |
| format | Article |
| id | mit-1721.1/90997 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:41:22Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/909972022-09-30T22:16:24Z Conceptual Modeling of mRNA Decay Provokes New Hypotheses Somekh, Judith Haimovich, Gal Guterman, Adi Dori, Dov Choder, Mordechai Massachusetts Institute of Technology. Engineering Systems Division Dori, Dov 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′-untralslated 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. 2014-10-20T17:48:56Z 2014-10-20T17:48:56Z 2014-09 2014-07 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/90997 Somekh, Judith, Gal Haimovich, Adi Guterman, Dov Dori, and Mordechai Choder. “Conceptual Modeling of mRNA Decay Provokes New Hypotheses.” Edited by Yoon Ki Kim. PLoS ONE 9, no. 9 (September 25, 2014): e107085. https://orcid.org/0000-0002-2393-3124 en_US http://dx.doi.org/10.1371/journal.pone.0107085 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Somekh, Judith Haimovich, Gal Guterman, Adi Dori, Dov Choder, Mordechai Conceptual Modeling of mRNA Decay Provokes New Hypotheses |
| title | 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_short | Conceptual Modeling of mRNA Decay Provokes New Hypotheses |
| title_sort | conceptual modeling of mrna decay provokes new hypotheses |
| url | http://hdl.handle.net/1721.1/90997 https://orcid.org/0000-0002-2393-3124 |
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