{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:30:18Z","timestamp":1761708618033,"version":"3.38.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Analysis and intervention in the dynamics of gene regulatory networks is at the heart of emerging efforts in the development of modern treatment of numerous ailments including cancer. The ultimate goal is to develop methods to intervene in the function of living organisms in order to drive cells away from a malignant state into a benign form. A serious limitation of much of the previous work in cancer network analysis is the use of external control, which requires intervention at each time step, for an indefinite time interval. This is in sharp contrast to the proposed approach, which relies on the solution of an inverse perturbation problem to introduce a one-time intervention in the structure of regulatory networks. This isolated intervention transforms the steady-state distribution of the dynamic system to the desired steady-state distribution.<\/jats:p><jats:p>Results: We formulate the optimal intervention problem in gene regulatory networks as a minimal perturbation of the network in order to force it to converge to a desired steady-state distribution of gene regulation. We cast optimal intervention in gene regulation as a convex optimization problem, thus providing a globally optimal solution which can be efficiently computed using standard toolboxes for convex optimization. The criteria adopted for optimality is chosen to minimize potential adverse effects as a consequence of the intervention strategy. We consider a perturbation that minimizes (i) the overall energy of change between the original and controlled networks and (ii) the time needed to reach the desired steady-state distribution of gene regulation. Furthermore, we show that there is an inherent trade-off between minimizing the energy of the perturbation and the convergence rate to the desired distribution. We apply the proposed control to the human melanoma gene regulatory network.<\/jats:p><jats:p>Availability: The MATLAB code for optimal intervention in gene regulatory networks can be found online: http:\/\/syen.ualr.edu\/nxbouaynaya\/Bioinformatics2010.html.<\/jats:p><jats:p>Contact: \u00a0nxbouaynaya@ualr.edu<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq605","type":"journal-article","created":{"date-parts":[[2010,11,10]],"date-time":"2010-11-10T01:25:36Z","timestamp":1289352336000},"page":"103-110","source":"Crossref","is-referenced-by-count":10,"title":["Inverse perturbation for optimal intervention in gene regulatory networks"],"prefix":"10.1093","volume":"27","author":[{"given":"Nidhal","family":"Bouaynaya","sequence":"first","affiliation":[{"name":"1 Department of Systems Engineering, University of Arkansas at Little Rock, Little Rock, AR 72204, 2Department of Mathematics, University of Alabama at Birmingham, Birmingham, AL 35294 and 3Department of Electrical and Computer Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Shterenberg","sequence":"additional","affiliation":[{"name":"1 Department of Systems Engineering, University of Arkansas at Little Rock, Little Rock, AR 72204, 2Department of Mathematics, University of Alabama at Birmingham, Birmingham, AL 35294 and 3Department of Electrical and Computer Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Schonfeld","sequence":"additional","affiliation":[{"name":"1 Department of Systems Engineering, University of Arkansas at Little Rock, Little Rock, AR 72204, 2Department of Mathematics, University of Alabama at Birmingham, Birmingham, AL 35294 and 3Department of Electrical and Computer Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,11,8]]},"reference":[{"key":"2023012511161091800_B1","first-page":"4621","article-title":"Implicit methods for probabilistic modeling of gene regulatory networks","author":"Abhishek","year":"2008","journal-title":"Annual International Conference of the IEEE Engineering in Medicine and Biology Society"},{"journal-title":"0 SDPpack: a package for semidefinite-quadratic-linear programming.","year":"1997","author":"Alizadeh","key":"2023012511161091800_B2"},{"volume-title":"Convex Optimization.","year":"2003","author":"Boyd","key":"2023012511161091800_B3"},{"key":"2023012511161091800_B4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1023\/A:1023909812213","article-title":"External control in markovian genetic regulatory networks","volume":"52","author":"Datta","year":"2003","journal-title":"Mach. 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