{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T23:13:01Z","timestamp":1695942781590},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The ability of cells to complete mitosis with high fidelity relies on elaborate checkpoint mechanisms. We study S- and M-phase checkpoint responses in silico in the budding yeast with a stochastic dynamical model for the cell-cycle. We aim to provide an unbiased functional classification of network interactions that reflect the contribution of each link to checkpoint efficiency in the presence of cellular fluctuations.<\/jats:p>\n               <jats:p>Results: We developed an algorithm BNetDyn to compute stochastic dynamical trajectories for an input gene network and its structural perturbations. User specified output measures like the mutual information between trigger and output nodes are then evaluated on the stationary state of the Markov process. Systematic perturbations of the yeast cell-cycle model by Li et al. classify each link according to its effect on checkpoint efficiencies and stabilities of the main cell-cycle phases. This points to the crosstalk in the cascades downstream of the SBF\/MBF transcription activator complexes as determinant for checkpoint optimality; a finding that consistently reflects recent experiments. Finally our stochastic analysis emphasizes how dynamical stability in the yeast cell-cycle network crucially relies on backward inhibitory circuits next to forward induction.<\/jats:p>\n               <jats:p>Availability: C++ source code and network models can be downloaded at<\/jats:p>\n               <jats:p>Contact: \u00a0felix.naef@isrec.ch<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btl432","type":"journal-article","created":{"date-parts":[[2006,8,9]],"date-time":"2006-08-09T03:27:36Z","timestamp":1155094056000},"page":"2539-2546","source":"Crossref","is-referenced-by-count":10,"title":["Few crucial links assure checkpoint efficiency in the yeast cell-cycle network"],"prefix":"10.1093","volume":"22","author":[{"given":"Gautier","family":"Stoll","sequence":"first","affiliation":[{"name":"Swiss Institute of Experimental Cancer Research, ISREC, NCCR Molecular Oncology 1 \u00a0 1 \u00a0 \u00a0 CH-1066 Epalinges, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Rougemont","sequence":"additional","affiliation":[{"name":"Swiss Institute of Bioinformatics, SIB 3 \u00a0 3 \u00a0 \u00a0 CH-1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e9lix","family":"Naef","sequence":"additional","affiliation":[{"name":"Swiss Institute of Experimental Cancer Research, ISREC, NCCR Molecular Oncology 1 \u00a0 1 \u00a0 \u00a0 CH-1066 Epalinges, Switzerland"},{"name":"Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, EPFL, School of Life Sciences 2 \u00a0 2 \u00a0 \u00a0 CH-1015 Lausanne, Switzerland"},{"name":"Swiss Institute of Bioinformatics, SIB 3 \u00a0 3 \u00a0 \u00a0 CH-1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,8,7]]},"reference":[{"key":"2023012409233449700_b1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.mrfmmm.2003.08.020","article-title":"G2 and spindle assembly checkpoint adaptation, and tetraploidy arrest: implications for intrinsic and chemically induced genomic instability","volume":"532","author":"Andreassen","year":"2003","journal-title":"Mutat Res."},{"key":"2023012409233449700_b2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/35002258","article-title":"Circadian clocks limited by noise","volume":"403","author":"Barkai","year":"2000","journal-title":"Nature"},{"key":"2023012409233449700_b3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1534\/genetics.105.044560","article-title":"High functional overlap between MluI cell-cycle box binding factor and Swi4\/6 cell-cycle box binding factor in the G1\/S transcriptional program in Saccharomyces cerevisiae","volume":"171","author":"Bean","year":"2005","journal-title":"Genetics"},{"key":"2023012409233449700_b4","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1126\/science.1113834","article-title":"Interlinked fast and slow positive feedback loops drive reliable cell decisions","volume":"310","author":"Brandman","year":"2005","journal-title":"Science"},{"key":"2023012409233449700_b5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jtbi.2005.01.023","article-title":"Robustness and fragility of Boolean models for genetic regulatory networks","volume":"235","author":"Chaves","year":"2005","journal-title":"J. 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