Design Principles of a Genetic Alarm Clock
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{"title"=>"Design Principles of a Genetic Alarm Clock", "type"=>"journal", "authors"=>[{"first_name"=>"Jaroslav", "last_name"=>"Albert", "scopus_author_id"=>"36992927700"}, {"first_name"=>"Marianne", "last_name"=>"Rooman", "scopus_author_id"=>"7003390020"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"366024972", "issn"=>"19326203", "pmid"=>"23144809", "doi"=>"10.1371/journal.pone.0047256", "sgr"=>"84868689354", "scopus"=>"2-s2.0-84868689354"}, "id"=>"795399a5-5565-359d-9177-7cd1c8af404f", "abstract"=>"Turning genes on and off is a mechanism by which cells and tissues make phenotypic decisions. Gene network motifs capable of supporting two or more steady states and thereby providing cells with a plurality of possible phenotypes are referred to as genetic switches. Modeled on the bases of naturally occurring genetic networks, synthetic biologists have successfully constructed artificial switches, thus opening a door to new possibilities for improvement of the known, but also the design of new synthetic genetic circuits. One of many obstacles to overcome in such efforts is to understand and hence control intrinsic noise which is inherent in all biological systems. For some motifs the noise is negligible; for others, fluctuations in the particle number can be comparable to its average. Due to their slowed dynamics, motifs with positive autoregulation tend to be highly sensitive to fluctuations of their chemical environment and are in general very noisy, especially during transition (switching). In this article we use stochastic simulations (Gillespie algorithm) to model such a system, in particular a simple bistable motif consisting of a single gene with positive autoregulation. Due to cooperativety, the dynamical behavior of this kind of motif is reminiscent of an alarm clock - the gene is (nearly) silent for some time after it is turned on and becomes active very suddenly. We investigate how these sudden transitions are affected by noise and show that under certain conditions accurate timing can be achieved. We also examine how promoter complexity influences the accuracy of this timing mechanism.", "link"=>"http://www.mendeley.com/research/design-principles-genetic-alarm-clock", "reader_count"=>14, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>10, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Norway"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/546142"], "description"=>"<p>A unique input was introduced at min for each case so as to generate a delay of 250 min. While for clarity only 10 runs are shown, the delay distribution (shown in the boxes) was computed from 100 runs. A clear difference in delay distribution can be seen between (a) and (b). The parameter values in inverse minutes are: in a) transcription rate , translation rate , TF association rate , TF dissociation rate, mRNA degradation rate , and protein degradation rate ; and in b) , , , , , and .</p>", "links"=>[], "tags"=>["tf"], "article_id"=>216642, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Simulation_of_TF_evolution_/216642", "title"=>"Simulation of TF evolution.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:36:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/546051"], "description"=>"<p>The evolution of mRNA and protein numbers are governed by the six processes shown: 1: Transcription; 2: mRNA degradation; 3: Translation; 4: Protein degradation; 5: TF-promoter associations; and 6: TF-promoter disassociation. Binding of 2 TFs to the promoter (activation site) enhances the transcription which in turn increases the rate of TF-promoter association.</p>", "links"=>[], "tags"=>["diagram"], "article_id"=>216554, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_diagram_of_the_gene_network_/216554", "title"=>"Schematic diagram of the gene network.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:35:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/546098"], "description"=>"<p>a) Plot of TF degradation rate, () and TF production rate as a function of – the fraction of TF concentration relative to its final steady state value. The difference is the net production. b) Plot of TF concentration as a function of time. c) A gene switch in an on (off) postion when (no) input is present: dot-dashed line (dashed line). d) Evolution of TF concentration for (solid line), with no input (dashed line), and with input (dot-dashed line). The small frame in (c) and (d) shows the situation for a single TAS.</p>", "links"=>[], "tags"=>["properties"], "article_id"=>216599, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dynamical_properties_a_system_with_positive_feedback_/216599", "title"=>"Dynamical properties a system with positive feedback.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:35:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/546347"], "description"=>"<p>Scatter plot of the relative delay uncertainty and the function of (Eq. (12)) for a) 2 TAS, min; b) 2 TAS, min; c) 3 TAS, min; and d) 3 TAS, min.</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>216844, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_delay_uncertainty_vs_F_/216844", "title"=>"Relative delay uncertainty vs. F.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:37:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/546406"], "description"=>"<p>Scatter plot of the relative delay uncertainty and the function of (Eq. (13)) for a) 2 TAS, min and min; b) 3TAS, min and min.</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>216909, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.g008", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_delay_uncertainty_vs_G_/216909", "title"=>"Relative delay uncertainty vs. G.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:37:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/546289"], "description"=>"<p>Scatter plot of the relative delay uncertainty and the function of (Eq. (13)) for a) 2 TAS, min; b) 2 TAS, min; c) 3 TAS, min; and d) 3 TAS, min.</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>216790, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.g006", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_delay_uncertainty_vs_G_/216790", "title"=>"Relative delay uncertainty vs. G.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:36:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/546194"], "description"=>"<p>This scatter plot indicates a linear relationship between the relative delay uncertainty and the relative difference of the observed average and deterministic delay . From an engineering point of view, this tells us that if one manages to reduce , is likely to be reduced as well.</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>216695, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_delay_shift_vs_relative_delay_uncertainty_/216695", "title"=>"Relative delay shift vs. relative delay uncertainty.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:36:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/546438"], "description"=>"<p>Results of predicted relative delay uncertainties and their variances for different coopereativities .</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>216938, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.t001", "stats"=>{"downloads"=>5, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Delay_uncertainty_predictions_/216938", "title"=>"Delay uncertainty predictions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 20:37:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/546237"], "description"=>"<p>Distribution of relative delay uncertainty for 2 and 3 TAS for a delay of 300 min (a) and 400 min (b). Each bar gives the fraction of all cases with between the values indicated on the x-axis in %.</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology"], "article_id"=>216734, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Jaroslav Albert", "Marianne Rooman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047256.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Uncertainty_distributions_/216734", "title"=>"Uncertainty distributions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:36:36"}

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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[316, 541, 663, 766, 856, 950, 1041, 1128, 1218, 1302, 1382, 1456, 1526, 1593, 1657, 1729, 1796, 1862, 1930, 1999, 2065, 2132, 2202, 2261, 2319]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[333, 576, 707, 814, 908, 1004, 1104, 1197, 1280, 1370, 1449, 1531, 1603, 1673, 1742, 1817, 1886, 1954, 2025, 2098, 2171, 2234, 2304, 2365, 2431]}, {"subject_area"=>"/Computer and information sciences", "average_usage"=>[352, 587, 696, 809, 901, 989, 1072, 1156, 1257, 1334, 1422, 1486, 1555, 1647, 1714, 1780, 1844, 1919, 1997, 2051, 2138, 2198, 2267, 2324, 2391]}, {"subject_area"=>"/Computer and information sciences/Systems science", "average_usage"=>[331, 552, 654, 739, 811, 881, 963, 1040, 1088, 1156, 1222, 1308, 1369, 1458, 1542, 1601, 1693, 1735, 1785, 1871, 1939, 2008, 2067, 2103, 2169]}, {"subject_area"=>"/Engineering and technology", "average_usage"=>[308, 500, 607, 700, 782, 876, 957, 1039, 1128, 1214, 1290, 1365, 1431, 1496, 1560, 1634, 1695, 1772, 1839, 1908, 1972, 2043, 2106, 2179, 2246]}, {"subject_area"=>"/Physical sciences/Mathematics", "average_usage"=>[325, 522, 627, 718, 804, 884, 969, 1052, 1131, 1207, 1277, 1346, 1415, 1478, 1542, 1605, 1663, 1723, 1776, 1839, 1895, 1955, 2008, 2066, 2123]}]}
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