Interrogating the topological robustness of gene regulatory circuits by randomization
Publication Date
March 31, 2017
Authors
Bin Huang, Mingyang Lu, Dongya Jia, Eshel Ben Jacob, et al
Volume
13
Issue
3
Pages
e1005456
DOI
https://dx.plos.org/10.1371/journal.pcbi.1005456
Publisher URL
http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1005456
Scopus
85016775880
Mendeley
http://www.mendeley.com/research/interrogating-topological-robustness-gene-regulatory-circuits-randomization
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Mendeley | Further Information

{"title"=>"Interrogating the topological robustness of gene regulatory circuits by randomization", "type"=>"journal", "authors"=>[{"first_name"=>"Bin", "last_name"=>"Huang", "scopus_author_id"=>"55907593800"}, {"first_name"=>"Mingyang", "last_name"=>"Lu", "scopus_author_id"=>"8954191100"}, {"first_name"=>"Dongya", "last_name"=>"Jia", "scopus_author_id"=>"56704339200"}, {"first_name"=>"Eshel", "last_name"=>"Ben-Jacob", "scopus_author_id"=>"7005078550"}, {"first_name"=>"Herbert", "last_name"=>"Levine", "scopus_author_id"=>"35399029700"}, {"first_name"=>"Jose N.", "last_name"=>"Onuchic", "scopus_author_id"=>"35602445700"}], "year"=>2017, "source"=>"PLoS Computational Biology", "identifiers"=>{"sgr"=>"85016775880", "doi"=>"10.1371/journal.pcbi.1005456", "isbn"=>"1111111111", "pmid"=>"28362798", "issn"=>"15537358", "scopus"=>"2-s2.0-85016775880", "pui"=>"615171134"}, "id"=>"0f4da615-c5fd-3b05-a234-7610e192c04d", "abstract"=>"One of the most important roles of cells is performing their cellular tasks properly for survival. Cells usually achieve robust functionality, for example, cell-fate decision-making and signal transduction, through multiple layers of regulation involving many genes. Despite the combinatorial complexity of gene regulation, its quantitative behavior has been typically studied on the basis of experimentally verified core gene regulatory circuitry, composed of a small set of important elements. It is still unclear how such a core circuit operates in the presence of many other regulatory molecules and in a crowded and noisy cellular environment. Here we report a new computational method, named random circuit perturbation (RACIPE), for interrogating the robust dynamical behavior of a gene regulatory circuit even without accurate measurements of circuit kinetic parameters. RACIPE generates an ensemble of random kinetic models corresponding to a fixed circuit topology, and utilizes statistical tools to identify generic properties of the circuit. By applying RACIPE to simple toggle-switch-like motifs, we observed that the stable states of all models converge to experimentally observed gene state clusters even when the parameters are strongly perturbed. RACIPE was further applied to a proposed 22-gene network of the Epithelial-to-Mesenchymal Transition (EMT), from which we identified four experimentally observed gene states, including the states that are associated with two different types of hybrid Epithelial/Mesenchymal phenotypes. Our results suggest that dynamics of a gene circuit is mainly determined by its topology, not by detailed circuit parameters. Our work provides a theoretical foundation for circuit-based systems biology modeling. We anticipate RACIPE to be a powerful tool to predict and decode circuit design principles in an unbiased manner, and to quantitatively evaluate the robustness and heterogeneity of gene expression.", "link"=>"http://www.mendeley.com/research/interrogating-topological-robustness-gene-regulatory-circuits-randomization", "reader_count"=>54, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>9, "Researcher"=>17, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>3, "Professor"=>5}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>9, "Researcher"=>17, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>3, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>16, "Agricultural and Biological Sciences"=>17, "Medicine and Dentistry"=>3, "Physics and Astronomy"=>6, "Chemical Engineering"=>1, "Chemistry"=>1, "Computer Science"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Computer Science"=>{"Computer Science"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>16}, "Unspecified"=>{"Unspecified"=>4}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"India"=>1}, "group_count"=>2}

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Scopus | Further Information

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