Show simple item record

dc.creatorYousofshahi, Monaen
dc.creatorOrshansky, Michaelen
dc.creatorLee, Kyongbumen
dc.creatorHassoun, Sohaen
dc.date.accessioned2014-12-15T17:11:00Zen
dc.date.available2014-12-15T17:11:00Zen
dc.date.issued2013-03-29en
dc.identifier.citationYousofshahi, Mona, Michael Orshansky, Kyongbum Lee, and Soha Hassoun. “Probabilistic Strain Optimization under Constraint Uncertainty.” BMC Systems Biology 7, no. 1 (March 29, 2013): 29. doi:10.1186/1752-0509-7-29.en
dc.identifier.urihttp://hdl.handle.net/2152/27963en
dc.descriptionMona Yousofshahi and Soha Hassoun are with the Department of Computer Science, Tufts University, Medford, MA, USA -- Michael Orshansky is with the Department of Electrical and Computer Engineering, University of Texas at Austin, Austin, TX, USA -- Kyongbum Lee is with the Department of Chemical and Biological Engineering, Tufts University, Medford, MA, USAen
dc.description.abstractBackground: An important step in strain optimization is to identify reactions whose activities should be modified to achieve the desired cellular objective. Preferably, these reactions are identified systematically, as the number of possible combinations of reaction modifications could be very large. Over the last several years, a number of computational methods have been described for identifying combinations of reaction modifications. However, none of these methods explicitly address uncertainties in implementing the reaction activity modifications. In this work, we model the uncertainties as probability distributions in the flux carrying capacities of reactions. Based on this model, we develop an optimization method that identifies reactions for flux capacity modifications to predict outcomes with high statistical likelihood. Results: We compare three optimization methods that select an intervention set comprising up- or down-regulation of reaction flux capacity: CCOpt (Chance constrained optimization), DetOpt (Deterministic optimization), and MCOpt (Monte Carlo-based optimization). We evaluate the methods using a Monte Carlo simulation-based method, MCEval (Monte Carlo Evaluations). We present two case studies analyzing a CHO cell and an adipocyte model. The flux capacity distributions required for our methods were estimated from maximal reaction velocities or elementary mode analysis. The intervention set selected by CCOpt consistently outperforms the intervention set selected by DetOpt in terms of tolerance to flux capacity variations. MCEval shows that the optimal flux predicted based on the CCOpt intervention set is more likely to be obtained, in a probabilistic sense, than the flux predicted by DetOpt. The intervention sets identified by CCOpt and MCOpt were similar; however, the exhaustive sampling required by MCOpt incurred significantly greater computational cost. Conclusions: Maximizing tolerance to variable engineering outcomes (in modifying enzyme activities) can identify intervention sets that statistically improve the desired cellular objective.en
dc.description.sponsorshipen
dc.language.isoEnglishen
dc.publisherBMC Systems Biologyen
dc.rightsAdministrative deposit of works to UT Digital Repository: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access at http://www.biomedcentral.com. The public license is specified as CC-BY: http://creativecommons.org/licenses/by/4.0/. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en
dc.subjectenzyme activity modificationen
dc.subjectflux capacityen
dc.subjectchance-constrained optimizationen
dc.titleProbabilistic strain optimization under constraint uncertaintyen
dc.typeArticleen
dc.description.departmentElectrical and Computer Engineeringen
dc.description.catalogingnotesoha@cs.tufts.eduen
dc.identifier.Filename1752-0509-7-29.pdfen
dc.identifier.doidoi:10.1186/1752-0509-7-29en


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record