TABASCO: A single molecule, base-pair resolved gene expression simulator
Background Experimental studies of gene expression have identified some of the individual molecular components and elementary reactions that comprise and control cellular behavior. Given our current understanding of gene expression, and the goals of biotechnology research, both scientists and engine...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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BioMed Central Ltd
2010
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| Online Access: | http://hdl.handle.net/1721.1/58757 https://orcid.org/0000-0002-4661-0600 |
| _version_ | 1811070029191446528 |
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| author | Kosuri, Sriram Endy, Drew Kelly, Jason R. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Kosuri, Sriram Endy, Drew Kelly, Jason R. |
| author_sort | Kosuri, Sriram |
| collection | MIT |
| description | Background Experimental studies of gene expression have identified some of the individual molecular components and elementary reactions that comprise and control cellular behavior. Given our current understanding of gene expression, and the goals of biotechnology research, both scientists and engineers would benefit from detailed simulators that can explicitly compute genome-wide expression levels as a function of individual molecular events, including the activities and interactions of molecules on DNA at single base pair resolution. However, for practical reasons including computational tractability, available simulators have not been able to represent genome-scale models of gene expression at this level of detail. Results Here we develop a simulator, TABASCO http://openwetware.org/wiki/TABASCO, which enables the precise representation of individual molecules and events in gene expression for genome-scale systems. We use a single molecule computational engine to track individual molecules interacting with and along nucleic acid polymers at single base resolution. Tabasco uses logical rules to automatically update and delimit the set of species and reactions that comprise a system during simulation, thereby avoiding the need for a priori specification of all possible combinations of molecules and reaction events. We confirm that single molecule, base-pair resolved simulation using TABASCO (Tabasco) can accurately compute gene expression dynamics and, moving beyond previous simulators, provide for the direct representation of intermolecular events such as polymerase collisions and promoter occlusion. We demonstrate the computational capacity of Tabasco by simulating the entirety of gene expression during bacteriophage T7 infection; for reference, the 39,937 base pair T7 genome encodes 56 genes that are transcribed by two types of RNA polymerases active across 22 promoters. Conclusion Tabasco enables genome-scale simulation of transcription and translation at individual molecule and single base-pair resolution. By directly representing the position and activity of individual molecules on DNA, Tabasco can directly test the effects of detailed molecular processes on system-wide gene expression. Tabasco would also be useful for studying the complex regulatory mechanisms controlling eukaryotic gene expression. The computational engine underlying Tabasco could also be adapted to represent other types of processive systems in which individual reaction events are organized across a single spatial dimension (e.g., polysaccharide synthesis). |
| first_indexed | 2024-09-23T08:21:18Z |
| format | Article |
| id | mit-1721.1/58757 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:21:18Z |
| publishDate | 2010 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/587572022-09-23T12:26:51Z TABASCO: A single molecule, base-pair resolved gene expression simulator Kosuri, Sriram Endy, Drew Kelly, Jason R. Massachusetts Institute of Technology. Department of Biological Engineering Endy, Drew Kelly, Jason R. Kosuri, Sriram Background Experimental studies of gene expression have identified some of the individual molecular components and elementary reactions that comprise and control cellular behavior. Given our current understanding of gene expression, and the goals of biotechnology research, both scientists and engineers would benefit from detailed simulators that can explicitly compute genome-wide expression levels as a function of individual molecular events, including the activities and interactions of molecules on DNA at single base pair resolution. However, for practical reasons including computational tractability, available simulators have not been able to represent genome-scale models of gene expression at this level of detail. Results Here we develop a simulator, TABASCO http://openwetware.org/wiki/TABASCO, which enables the precise representation of individual molecules and events in gene expression for genome-scale systems. We use a single molecule computational engine to track individual molecules interacting with and along nucleic acid polymers at single base resolution. Tabasco uses logical rules to automatically update and delimit the set of species and reactions that comprise a system during simulation, thereby avoiding the need for a priori specification of all possible combinations of molecules and reaction events. We confirm that single molecule, base-pair resolved simulation using TABASCO (Tabasco) can accurately compute gene expression dynamics and, moving beyond previous simulators, provide for the direct representation of intermolecular events such as polymerase collisions and promoter occlusion. We demonstrate the computational capacity of Tabasco by simulating the entirety of gene expression during bacteriophage T7 infection; for reference, the 39,937 base pair T7 genome encodes 56 genes that are transcribed by two types of RNA polymerases active across 22 promoters. Conclusion Tabasco enables genome-scale simulation of transcription and translation at individual molecule and single base-pair resolution. By directly representing the position and activity of individual molecules on DNA, Tabasco can directly test the effects of detailed molecular processes on system-wide gene expression. Tabasco would also be useful for studying the complex regulatory mechanisms controlling eukaryotic gene expression. The computational engine underlying Tabasco could also be adapted to represent other types of processive systems in which individual reaction events are organized across a single spatial dimension (e.g., polysaccharide synthesis). MIT/NIGMS Biotechnology Training Program Fellowship National Institute of General Medical Sciences (U.S.) Massachusetts Institute of Technology Andrew and Edna Viterbi Fellowship in Computational Biology National Science Foundation (U.S.) 2010-09-29T15:40:22Z 2010-09-29T15:40:22Z 2007-12 2007-05 2010-09-03T16:19:29Z Article http://purl.org/eprint/type/JournalArticle 1471-2105 http://hdl.handle.net/1721.1/58757 Kosuri, Sriram, Jason Kelly, and Drew Endy. “TABASCO: A single molecule, base-pair resolved gene expression simulator.” BMC Bioinformatics 8.1 (2007): 480. 18093293 https://orcid.org/0000-0002-4661-0600 en http://dx.doi.org/10.1186/1471-2105-8-480 BMC Bioinformatics Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Kosuri et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Kosuri, Sriram Endy, Drew Kelly, Jason R. TABASCO: A single molecule, base-pair resolved gene expression simulator |
| title | TABASCO: A single molecule, base-pair resolved gene expression simulator |
| title_full | TABASCO: A single molecule, base-pair resolved gene expression simulator |
| title_fullStr | TABASCO: A single molecule, base-pair resolved gene expression simulator |
| title_full_unstemmed | TABASCO: A single molecule, base-pair resolved gene expression simulator |
| title_short | TABASCO: A single molecule, base-pair resolved gene expression simulator |
| title_sort | tabasco a single molecule base pair resolved gene expression simulator |
| url | http://hdl.handle.net/1721.1/58757 https://orcid.org/0000-0002-4661-0600 |
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