--- _id: '7147' abstract: - lang: eng text: "The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets.\r\n\r\nIn this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest.\r\n\r\nThe behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions." alternative_title: - LNCS article_processing_charge: No author: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 - first_name: Ali full_name: Sezgin, Ali id: 4C7638DA-F248-11E8-B48F-1D18A9856A87 last_name: Sezgin citation: ama: 'Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. Transient memory in gene regulation. In: 17th International Conference on Computational Methods in Systems Biology. Vol 11773. Springer Nature; 2019:155-187. doi:10.1007/978-3-030-31304-3_9' apa: 'Guet, C. C., Henzinger, T. A., Igler, C., Petrov, T., & Sezgin, A. (2019). Transient memory in gene regulation. In 17th International Conference on Computational Methods in Systems Biology (Vol. 11773, pp. 155–187). Trieste, Italy: Springer Nature. https://doi.org/10.1007/978-3-030-31304-3_9' chicago: Guet, Calin C, Thomas A Henzinger, Claudia Igler, Tatjana Petrov, and Ali Sezgin. “Transient Memory in Gene Regulation.” In 17th International Conference on Computational Methods in Systems Biology, 11773:155–87. Springer Nature, 2019. https://doi.org/10.1007/978-3-030-31304-3_9. ieee: C. C. Guet, T. A. Henzinger, C. Igler, T. Petrov, and A. Sezgin, “Transient memory in gene regulation,” in 17th International Conference on Computational Methods in Systems Biology, Trieste, Italy, 2019, vol. 11773, pp. 155–187. ista: 'Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. 2019. Transient memory in gene regulation. 17th International Conference on Computational Methods in Systems Biology. CMSB: Computational Methods in Systems Biology, LNCS, vol. 11773, 155–187.' mla: Guet, Calin C., et al. “Transient Memory in Gene Regulation.” 17th International Conference on Computational Methods in Systems Biology, vol. 11773, Springer Nature, 2019, pp. 155–87, doi:10.1007/978-3-030-31304-3_9. short: C.C. Guet, T.A. Henzinger, C. Igler, T. Petrov, A. Sezgin, in:, 17th International Conference on Computational Methods in Systems Biology, Springer Nature, 2019, pp. 155–187. conference: end_date: 2019-09-20 location: Trieste, Italy name: 'CMSB: Computational Methods in Systems Biology' start_date: 2019-09-18 date_created: 2019-12-04T16:07:50Z date_published: 2019-09-17T00:00:00Z date_updated: 2023-09-06T11:18:08Z day: '17' department: - _id: CaGu - _id: ToHe doi: 10.1007/978-3-030-31304-3_9 external_id: isi: - '000557875100009' intvolume: ' 11773' isi: 1 language: - iso: eng month: '09' oa_version: None page: 155-187 project: - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize - _id: 251EE76E-B435-11E9-9278-68D0E5697425 grant_number: '24573' name: Design principles underlying genetic switch architecture publication: 17th International Conference on Computational Methods in Systems Biology publication_identifier: eissn: - 1611-3349 isbn: - '9783030313036' - '9783030313043' issn: - 0302-9743 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Transient memory in gene regulation type: conference user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 11773 year: '2019' ... --- _id: '471' abstract: - lang: eng text: 'We present a new algorithm for the statistical model checking of Markov chains with respect to unbounded temporal properties, including full linear temporal logic. The main idea is that we monitor each simulation run on the fly, in order to detect quickly if a bottom strongly connected component is entered with high probability, in which case the simulation run can be terminated early. As a result, our simulation runs are often much shorter than required by termination bounds that are computed a priori for a desired level of confidence on a large state space. In comparison to previous algorithms for statistical model checking our method is not only faster in many cases but also requires less information about the system, namely, only the minimum transition probability that occurs in the Markov chain. In addition, our method can be generalised to unbounded quantitative properties such as mean-payoff bounds. ' article_number: '12' author: - first_name: Przemyslaw full_name: Daca, Przemyslaw id: 49351290-F248-11E8-B48F-1D18A9856A87 last_name: Daca - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Jan full_name: Kretinsky, Jan id: 44CEF464-F248-11E8-B48F-1D18A9856A87 last_name: Kretinsky orcid: 0000-0002-8122-2881 - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: Daca P, Henzinger TA, Kretinsky J, Petrov T. Faster statistical model checking for unbounded temporal properties. ACM Transactions on Computational Logic (TOCL). 2017;18(2). doi:10.1145/3060139 apa: Daca, P., Henzinger, T. A., Kretinsky, J., & Petrov, T. (2017). Faster statistical model checking for unbounded temporal properties. ACM Transactions on Computational Logic (TOCL). ACM. https://doi.org/10.1145/3060139 chicago: Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Faster Statistical Model Checking for Unbounded Temporal Properties.” ACM Transactions on Computational Logic (TOCL). ACM, 2017. https://doi.org/10.1145/3060139. ieee: P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Faster statistical model checking for unbounded temporal properties,” ACM Transactions on Computational Logic (TOCL), vol. 18, no. 2. ACM, 2017. ista: Daca P, Henzinger TA, Kretinsky J, Petrov T. 2017. Faster statistical model checking for unbounded temporal properties. ACM Transactions on Computational Logic (TOCL). 18(2), 12. mla: Daca, Przemyslaw, et al. “Faster Statistical Model Checking for Unbounded Temporal Properties.” ACM Transactions on Computational Logic (TOCL), vol. 18, no. 2, 12, ACM, 2017, doi:10.1145/3060139. short: P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, ACM Transactions on Computational Logic (TOCL) 18 (2017). date_created: 2018-12-11T11:46:39Z date_published: 2017-05-01T00:00:00Z date_updated: 2023-02-21T16:48:11Z day: '01' department: - _id: ToHe doi: 10.1145/3060139 ec_funded: 1 intvolume: ' 18' issue: '2' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1504.05739 month: '05' oa: 1 oa_version: Submitted Version project: - _id: 25EE3708-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '267989' name: Quantitative Reactive Modeling - _id: 25F5A88A-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S11402-N23 name: Moderne Concurrency Paradigms - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: ACM Transactions on Computational Logic (TOCL) publication_identifier: issn: - '15293785' publication_status: published publisher: ACM publist_id: '7349' quality_controlled: '1' related_material: record: - id: '1234' relation: earlier_version status: public scopus_import: 1 status: public title: Faster statistical model checking for unbounded temporal properties type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 18 year: '2017' ... --- _id: '1351' abstract: - lang: eng text: The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights. article_processing_charge: No author: - first_name: Mirco full_name: Giacobbe, Mirco id: 3444EA5E-F248-11E8-B48F-1D18A9856A87 last_name: Giacobbe orcid: 0000-0001-8180-0904 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Ashutosh full_name: Gupta, Ashutosh id: 335E5684-F248-11E8-B48F-1D18A9856A87 last_name: Gupta - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking the evolution of gene regulatory networks. Acta Informatica. 2017;54(8):765-787. doi:10.1007/s00236-016-0278-x apa: Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov, T. (2017). Model checking the evolution of gene regulatory networks. Acta Informatica. Springer. https://doi.org/10.1007/s00236-016-0278-x chicago: Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica. Springer, 2017. https://doi.org/10.1007/s00236-016-0278-x. ieee: M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking the evolution of gene regulatory networks,” Acta Informatica, vol. 54, no. 8. Springer, pp. 765–787, 2017. ista: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2017. Model checking the evolution of gene regulatory networks. Acta Informatica. 54(8), 765–787. mla: Giacobbe, Mirco, et al. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica, vol. 54, no. 8, Springer, 2017, pp. 765–87, doi:10.1007/s00236-016-0278-x. short: M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, Acta Informatica 54 (2017) 765–787. date_created: 2018-12-11T11:51:32Z date_published: 2017-12-01T00:00:00Z date_updated: 2023-09-20T11:06:03Z day: '01' ddc: - '006' - '576' department: - _id: ToHe - _id: CaGu - _id: NiBa doi: 10.1007/s00236-016-0278-x ec_funded: 1 external_id: isi: - '000414343200003' file: - access_level: open_access checksum: 4e661d9135d7f8c342e8e258dee76f3e content_type: application/pdf creator: dernst date_created: 2019-01-17T15:57:29Z date_updated: 2020-07-14T12:44:46Z file_id: '5841' file_name: 2017_ActaInformatica_Giacobbe.pdf file_size: 755241 relation: main_file file_date_updated: 2020-07-14T12:44:46Z has_accepted_license: '1' intvolume: ' 54' isi: 1 issue: '8' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 765 - 787 project: - _id: 25EE3708-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '267989' name: Quantitative Reactive Modeling - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 25B07788-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '250152' name: Limits to selection in biology and in evolutionary computation publication: Acta Informatica publication_identifier: issn: - '00015903' publication_status: published publisher: Springer publist_id: '5898' pubrep_id: '649' quality_controlled: '1' related_material: record: - id: '1835' relation: earlier_version status: public scopus_import: '1' status: public title: Model checking the evolution of gene regulatory networks tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 54 year: '2017' ... --- _id: '1524' abstract: - lang: eng text: "When designing genetic circuits, the typical primitives used in major existing modelling formalisms are gene interaction graphs, where edges between genes denote either an activation or inhibition relation. However, when designing experiments, it is important to be precise about the low-level mechanistic details as to how each such relation is implemented. The rule-based modelling language Kappa allows to unambiguously specify mechanistic details such as DNA binding sites, dimerisation of transcription factors, or co-operative interactions. Such a detailed description comes with complexity and computationally costly executions. We propose a general method for automatically transforming a rule-based program, by eliminating intermediate species and adjusting the rate constants accordingly. To the best of our knowledge, we show the first automated reduction of rule-based models based on equilibrium approximations.\r\nOur algorithm is an adaptation of an existing algorithm, which was designed for reducing reaction-based programs; our version of the algorithm scans the rule-based Kappa model in search for those interaction patterns known to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). Additional checks are then performed in order to verify if the reduction is meaningful in the context of the full model. The reduced model is efficiently obtained by static inspection over the rule-set. The tool is tested on a detailed rule-based model of a λ-phage switch, which lists 92 rules and 13 agents. The reduced model has 11 rules and 5 agents, and provides a dramatic reduction in simulation time of several orders of magnitude." acknowledgement: This research was supported by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734, and the SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2_148797. alternative_title: - LNCS author: - first_name: Andreea full_name: Beica, Andreea last_name: Beica - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: 'Beica A, Guet CC, Petrov T. Efficient reduction of kappa models by static inspection of the rule-set. In: Vol 9271. Springer; 2016:173-191. doi:10.1007/978-3-319-26916-0_10' apa: 'Beica, A., Guet, C. C., & Petrov, T. (2016). Efficient reduction of kappa models by static inspection of the rule-set (Vol. 9271, pp. 173–191). Presented at the HSB: Hybrid Systems Biology, Madrid, Spain: Springer. https://doi.org/10.1007/978-3-319-26916-0_10' chicago: Beica, Andreea, Calin C Guet, and Tatjana Petrov. “Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set,” 9271:173–91. Springer, 2016. https://doi.org/10.1007/978-3-319-26916-0_10. ieee: 'A. Beica, C. C. Guet, and T. Petrov, “Efficient reduction of kappa models by static inspection of the rule-set,” presented at the HSB: Hybrid Systems Biology, Madrid, Spain, 2016, vol. 9271, pp. 173–191.' ista: 'Beica A, Guet CC, Petrov T. 2016. Efficient reduction of kappa models by static inspection of the rule-set. HSB: Hybrid Systems Biology, LNCS, vol. 9271, 173–191.' mla: Beica, Andreea, et al. Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set. Vol. 9271, Springer, 2016, pp. 173–91, doi:10.1007/978-3-319-26916-0_10. short: A. Beica, C.C. Guet, T. Petrov, in:, Springer, 2016, pp. 173–191. conference: end_date: 2015-09-05 location: Madrid, Spain name: 'HSB: Hybrid Systems Biology' start_date: 2015-09-04 date_created: 2018-12-11T11:52:31Z date_published: 2016-01-10T00:00:00Z date_updated: 2021-01-12T06:51:22Z day: '10' department: - _id: CaGu - _id: ToHe doi: 10.1007/978-3-319-26916-0_10 ec_funded: 1 intvolume: ' 9271' language: - iso: eng main_file_link: - open_access: '1' url: http://arxiv.org/abs/1501.00440 month: '01' oa: 1 oa_version: Preprint page: 173 - 191 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication_status: published publisher: Springer publist_id: '5649' quality_controlled: '1' scopus_import: 1 status: public title: Efficient reduction of kappa models by static inspection of the rule-set type: conference user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 9271 year: '2016' ... --- _id: '1093' abstract: - lang: eng text: 'We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results. ' acknowledgement: "This research was funded in part by the European Research Council (ERC) under grant agreement 267989\r\n(QUAREM), the Austrian Science Fund (FWF) under grants project S11402-N23 (RiSE and SHiNE)\r\nand Z211-N23 (Wittgenstein Award), by the Czech Science Foundation Grant No. P202/12/G061, and\r\nby the SNSF Advanced Postdoc. Mobility Fellowship – grant number P300P2_161067." alternative_title: - LIPIcs article_number: '20' author: - first_name: Przemyslaw full_name: Daca, Przemyslaw id: 49351290-F248-11E8-B48F-1D18A9856A87 last_name: Daca - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Jan full_name: Kretinsky, Jan id: 44CEF464-F248-11E8-B48F-1D18A9856A87 last_name: Kretinsky orcid: 0000-0002-8122-2881 - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: 'Daca P, Henzinger TA, Kretinsky J, Petrov T. Linear distances between Markov chains. In: Vol 59. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2016. doi:10.4230/LIPIcs.CONCUR.2016.20' apa: 'Daca, P., Henzinger, T. A., Kretinsky, J., & Petrov, T. (2016). Linear distances between Markov chains (Vol. 59). Presented at the CONCUR: Concurrency Theory, Quebec City; Canada: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. https://doi.org/10.4230/LIPIcs.CONCUR.2016.20' chicago: Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Linear Distances between Markov Chains,” Vol. 59. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016. https://doi.org/10.4230/LIPIcs.CONCUR.2016.20. ieee: 'P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Linear distances between Markov chains,” presented at the CONCUR: Concurrency Theory, Quebec City; Canada, 2016, vol. 59.' ista: 'Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Linear distances between Markov chains. CONCUR: Concurrency Theory, LIPIcs, vol. 59, 20.' mla: Daca, Przemyslaw, et al. Linear Distances between Markov Chains. Vol. 59, 20, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016, doi:10.4230/LIPIcs.CONCUR.2016.20. short: P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016. conference: end_date: 2016-08-26 location: Quebec City; Canada name: 'CONCUR: Concurrency Theory' start_date: 2016-08-23 date_created: 2018-12-11T11:50:06Z date_published: 2016-08-01T00:00:00Z date_updated: 2023-09-07T11:58:33Z day: '01' ddc: - '004' department: - _id: ToHe - _id: KrCh - _id: CaGu doi: 10.4230/LIPIcs.CONCUR.2016.20 ec_funded: 1 file: - access_level: open_access content_type: application/pdf creator: system date_created: 2018-12-12T10:11:39Z date_updated: 2018-12-12T10:11:39Z file_id: '4895' file_name: IST-2017-794-v1+1_LIPIcs-CONCUR-2016-20.pdf file_size: 501827 relation: main_file file_date_updated: 2018-12-12T10:11:39Z has_accepted_license: '1' intvolume: ' 59' language: - iso: eng month: '08' oa: 1 oa_version: Published Version project: - _id: 25EE3708-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '267989' name: Quantitative Reactive Modeling - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize publication_status: published publisher: Schloss Dagstuhl - Leibniz-Zentrum für Informatik publist_id: '6283' pubrep_id: '794' quality_controlled: '1' related_material: record: - id: '1155' relation: dissertation_contains status: public scopus_import: 1 status: public title: Linear distances between Markov chains tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: conference user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 59 year: '2016' ... --- _id: '1234' abstract: - lang: eng text: We present a new algorithm for the statistical model checking of Markov chains with respect to unbounded temporal properties, including full linear temporal logic. The main idea is that we monitor each simulation run on the fly, in order to detect quickly if a bottom strongly connected component is entered with high probability, in which case the simulation run can be terminated early. As a result, our simulation runs are often much shorter than required by termination bounds that are computed a priori for a desired level of confidence on a large state space. In comparison to previous algorithms for statistical model checking our method is not only faster in many cases but also requires less information about the system, namely, only the minimum transition probability that occurs in the Markov chain. In addition, our method can be generalised to unbounded quantitative properties such as mean-payoff bounds. acknowledgement: "This research was funded in part by the European Research Council (ERC) under\r\ngrant agreement 267989 (QUAREM), the Austrian Science Fund \ (FWF) under\r\ngrants project S11402-N23 (RiSE) and Z211-N23 (Wittgenstein Award), the Peo-\r\nple Programme (Marie Curie Actions) of the European Union’s Seventh Framework\r\nProgramme (FP7/2007-2013) REA Grant No 291734, the SNSF Advanced Postdoc.\r\nMobility Fellowship – grant number P300P2\r\n161067, and the Czech Science Foun-\r\ndation under grant agreement P202/12/G061." alternative_title: - LNCS author: - first_name: Przemyslaw full_name: Daca, Przemyslaw id: 49351290-F248-11E8-B48F-1D18A9856A87 last_name: Daca - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Jan full_name: Kretinsky, Jan id: 44CEF464-F248-11E8-B48F-1D18A9856A87 last_name: Kretinsky orcid: 0000-0002-8122-2881 - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: 'Daca P, Henzinger TA, Kretinsky J, Petrov T. Faster statistical model checking for unbounded temporal properties. In: Vol 9636. Springer; 2016:112-129. doi:10.1007/978-3-662-49674-9_7' apa: 'Daca, P., Henzinger, T. A., Kretinsky, J., & Petrov, T. (2016). Faster statistical model checking for unbounded temporal properties (Vol. 9636, pp. 112–129). Presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands: Springer. https://doi.org/10.1007/978-3-662-49674-9_7' chicago: Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Faster Statistical Model Checking for Unbounded Temporal Properties,” 9636:112–29. Springer, 2016. https://doi.org/10.1007/978-3-662-49674-9_7. ieee: 'P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Faster statistical model checking for unbounded temporal properties,” presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands, 2016, vol. 9636, pp. 112–129.' ista: 'Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Faster statistical model checking for unbounded temporal properties. TACAS: Tools and Algorithms for the Construction and Analysis of Systems, LNCS, vol. 9636, 112–129.' mla: Daca, Przemyslaw, et al. Faster Statistical Model Checking for Unbounded Temporal Properties. Vol. 9636, Springer, 2016, pp. 112–29, doi:10.1007/978-3-662-49674-9_7. short: P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Springer, 2016, pp. 112–129. conference: end_date: 2016-04-08 location: Eindhoven, The Netherlands name: 'TACAS: Tools and Algorithms for the Construction and Analysis of Systems' start_date: 2016-04-02 date_created: 2018-12-11T11:50:51Z date_published: 2016-01-01T00:00:00Z date_updated: 2023-09-07T11:58:33Z day: '01' department: - _id: ToHe - _id: CaGu doi: 10.1007/978-3-662-49674-9_7 ec_funded: 1 intvolume: ' 9636' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1504.05739 month: '01' oa: 1 oa_version: Preprint page: 112 - 129 project: - _id: 25EE3708-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '267989' name: Quantitative Reactive Modeling - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication_status: published publisher: Springer publist_id: '6099' quality_controlled: '1' related_material: record: - id: '471' relation: later_version status: public - id: '1155' relation: dissertation_contains status: public scopus_import: 1 status: public title: Faster statistical model checking for unbounded temporal properties type: conference user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 9636 year: '2016' ... --- _id: '1840' abstract: - lang: eng text: In this paper, we present a method for reducing a regular, discrete-time Markov chain (DTMC) to another DTMC with a given, typically much smaller number of states. The cost of reduction is defined as the Kullback-Leibler divergence rate between a projection of the original process through a partition function and a DTMC on the correspondingly partitioned state space. Finding the reduced model with minimal cost is computationally expensive, as it requires an exhaustive search among all state space partitions, and an exact evaluation of the reduction cost for each candidate partition. Our approach deals with the latter problem by minimizing an upper bound on the reduction cost instead of minimizing the exact cost. The proposed upper bound is easy to compute and it is tight if the original chain is lumpable with respect to the partition. Then, we express the problem in the form of information bottleneck optimization, and propose using the agglomerative information bottleneck algorithm for searching a suboptimal partition greedily, rather than exhaustively. The theory is illustrated with examples and one application scenario in the context of modeling bio-molecular interactions. acknowledgement: "This work was supported by the Austrian Research Association under Project 06/12684, by the Swiss National Science Foundation (SNSF) under Grant PP00P2 128503/1, by the SystemsX.ch (the Swiss Inititative for Systems Biology), and by a SNSF Early Postdoc.Mobility Fellowship grant P2EZP2_148797.\r\n" author: - first_name: Bernhard full_name: Geiger, Bernhard last_name: Geiger - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 - first_name: Gernot full_name: Kubin, Gernot last_name: Kubin - first_name: Heinz full_name: Koeppl, Heinz last_name: Koeppl citation: ama: Geiger B, Petrov T, Kubin G, Koeppl H. Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. 2015;60(4):1010-1022. doi:10.1109/TAC.2014.2364971 apa: Geiger, B., Petrov, T., Kubin, G., & Koeppl, H. (2015). Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. IEEE. https://doi.org/10.1109/TAC.2014.2364971 chicago: Geiger, Bernhard, Tatjana Petrov, Gernot Kubin, and Heinz Koeppl. “Optimal Kullback-Leibler Aggregation via Information Bottleneck.” IEEE Transactions on Automatic Control. IEEE, 2015. https://doi.org/10.1109/TAC.2014.2364971. ieee: B. Geiger, T. Petrov, G. Kubin, and H. Koeppl, “Optimal Kullback-Leibler aggregation via information bottleneck,” IEEE Transactions on Automatic Control, vol. 60, no. 4. IEEE, pp. 1010–1022, 2015. ista: Geiger B, Petrov T, Kubin G, Koeppl H. 2015. Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. 60(4), 1010–1022. mla: Geiger, Bernhard, et al. “Optimal Kullback-Leibler Aggregation via Information Bottleneck.” IEEE Transactions on Automatic Control, vol. 60, no. 4, IEEE, 2015, pp. 1010–22, doi:10.1109/TAC.2014.2364971. short: B. Geiger, T. Petrov, G. Kubin, H. Koeppl, IEEE Transactions on Automatic Control 60 (2015) 1010–1022. date_created: 2018-12-11T11:54:18Z date_published: 2015-04-01T00:00:00Z date_updated: 2021-01-12T06:53:33Z day: '01' department: - _id: CaGu - _id: ToHe doi: 10.1109/TAC.2014.2364971 intvolume: ' 60' issue: '4' language: - iso: eng main_file_link: - open_access: '1' url: http://arxiv.org/abs/1304.6603 month: '04' oa: 1 oa_version: Preprint page: 1010 - 1022 publication: IEEE Transactions on Automatic Control publication_identifier: issn: - 0018-9286 publication_status: published publisher: IEEE publist_id: '5262' quality_controlled: '1' scopus_import: 1 status: public title: Optimal Kullback-Leibler aggregation via information bottleneck type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 60 year: '2015' ... --- _id: '1835' abstract: - lang: eng text: The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs –an important problem of interest in evolutionary biology– more efficiently than the classical simulation method. We specify the property in linear temporal logics. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights. acknowledgement: "SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2 148797.\r\n" alternative_title: - LNCS author: - first_name: Mirco full_name: Giacobbe, Mirco id: 3444EA5E-F248-11E8-B48F-1D18A9856A87 last_name: Giacobbe orcid: 0000-0001-8180-0904 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Ashutosh full_name: Gupta, Ashutosh id: 335E5684-F248-11E8-B48F-1D18A9856A87 last_name: Gupta - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking gene regulatory networks. 2015;9035:469-483. doi:10.1007/978-3-662-46681-0_47 apa: 'Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov, T. (2015). Model checking gene regulatory networks. Presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, London, United Kingdom: Springer. https://doi.org/10.1007/978-3-662-46681-0_47' chicago: Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking Gene Regulatory Networks.” Lecture Notes in Computer Science. Springer, 2015. https://doi.org/10.1007/978-3-662-46681-0_47. ieee: M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking gene regulatory networks,” vol. 9035. Springer, pp. 469–483, 2015. ista: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2015. Model checking gene regulatory networks. 9035, 469–483. mla: Giacobbe, Mirco, et al. Model Checking Gene Regulatory Networks. Vol. 9035, Springer, 2015, pp. 469–83, doi:10.1007/978-3-662-46681-0_47. short: M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, 9035 (2015) 469–483. conference: end_date: 2015-04-18 location: London, United Kingdom name: 'TACAS: Tools and Algorithms for the Construction and Analysis of Systems' start_date: 2015-04-11 date_created: 2018-12-11T11:54:16Z date_published: 2015-04-01T00:00:00Z date_updated: 2023-09-20T11:06:03Z day: '01' department: - _id: ToHe - _id: CaGu - _id: NiBa doi: 10.1007/978-3-662-46681-0_47 ec_funded: 1 intvolume: ' 9035' language: - iso: eng main_file_link: - open_access: '1' url: http://arxiv.org/abs/1410.7704 month: '04' oa: 1 oa_version: Preprint page: 469 - 483 project: - _id: 25EE3708-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '267989' name: Quantitative Reactive Modeling - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation - _id: 25B07788-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '250152' name: Limits to selection in biology and in evolutionary computation - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication_status: published publisher: Springer publist_id: '5267' quality_controlled: '1' related_material: record: - id: '1351' relation: later_version status: public scopus_import: 1 series_title: Lecture Notes in Computer Science status: public title: Model checking gene regulatory networks type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 9035 year: '2015' ... --- _id: '2056' abstract: - lang: eng text: 'We consider a continuous-time Markov chain (CTMC) whose state space is partitioned into aggregates, and each aggregate is assigned a probability measure. A sufficient condition for defining a CTMC over the aggregates is presented as a variant of weak lumpability, which also characterizes that the measure over the original process can be recovered from that of the aggregated one. We show how the applicability of de-aggregation depends on the initial distribution. The application section is devoted to illustrate how the developed theory aids in reducing CTMC models of biochemical systems particularly in connection to protein-protein interactions. We assume that the model is written by a biologist in form of site-graph-rewrite rules. Site-graph-rewrite rules compactly express that, often, only a local context of a protein (instead of a full molecular species) needs to be in a certain configuration in order to trigger a reaction event. This observation leads to suitable aggregate Markov chains with smaller state spaces, thereby providing sufficient reduction in computational complexity. This is further exemplified in two case studies: simple unbounded polymerization and early EGFR/insulin crosstalk.' acknowledgement: T. Petrov is supported by SystemsX.ch—the Swiss Inititative for Systems Biology. author: - first_name: Arnab full_name: Ganguly, Arnab last_name: Ganguly - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 - first_name: Heinz full_name: Koeppl, Heinz last_name: Koeppl citation: ama: Ganguly A, Petrov T, Koeppl H. Markov chain aggregation and its applications to combinatorial reaction networks. Journal of Mathematical Biology. 2014;69(3):767-797. doi:10.1007/s00285-013-0738-7 apa: Ganguly, A., Petrov, T., & Koeppl, H. (2014). Markov chain aggregation and its applications to combinatorial reaction networks. Journal of Mathematical Biology. Springer. https://doi.org/10.1007/s00285-013-0738-7 chicago: Ganguly, Arnab, Tatjana Petrov, and Heinz Koeppl. “Markov Chain Aggregation and Its Applications to Combinatorial Reaction Networks.” Journal of Mathematical Biology. Springer, 2014. https://doi.org/10.1007/s00285-013-0738-7. ieee: A. Ganguly, T. Petrov, and H. Koeppl, “Markov chain aggregation and its applications to combinatorial reaction networks,” Journal of Mathematical Biology, vol. 69, no. 3. Springer, pp. 767–797, 2014. ista: Ganguly A, Petrov T, Koeppl H. 2014. Markov chain aggregation and its applications to combinatorial reaction networks. Journal of Mathematical Biology. 69(3), 767–797. mla: Ganguly, Arnab, et al. “Markov Chain Aggregation and Its Applications to Combinatorial Reaction Networks.” Journal of Mathematical Biology, vol. 69, no. 3, Springer, 2014, pp. 767–97, doi:10.1007/s00285-013-0738-7. short: A. Ganguly, T. Petrov, H. Koeppl, Journal of Mathematical Biology 69 (2014) 767–797. date_created: 2018-12-11T11:55:28Z date_published: 2014-11-20T00:00:00Z date_updated: 2021-01-12T06:55:01Z day: '20' department: - _id: CaGu - _id: ToHe doi: 10.1007/s00285-013-0738-7 intvolume: ' 69' issue: '3' language: - iso: eng main_file_link: - open_access: '1' url: http://arxiv.org/abs/1303.4532 month: '11' oa: 1 oa_version: Submitted Version page: 767 - 797 publication: Journal of Mathematical Biology publication_status: published publisher: Springer publist_id: '4990' quality_controlled: '1' scopus_import: 1 status: public title: Markov chain aggregation and its applications to combinatorial reaction networks type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 69 year: '2014' ... --- _id: '1913' abstract: - lang: eng text: 'Deposits of phosphorylated tau protein and convergence of pathology in the hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed to evaluate whether regional and cellular vulnerability patterns in the hippocampus distinguish tauopathies or are influenced by their concomitant presence. Methods: We created a heat map of phospho-tau (AT8) immunoreactivity patterns in 24 hippocampal subregions/layers in individuals with Alzheimer''s disease (AD)-related neurofibrillary degeneration (n = 40), Pick''s disease (n = 8), progressive supranuclear palsy (n = 7), corticobasal degeneration (n = 6), argyrophilic grain disease (AGD, n = 18), globular glial tauopathy (n = 5), and tau-astrogliopathy of the elderly (n = 10). AT8 immunoreactivity patterns were compared by mathematical analysis. Results: Our study reveals disease-specific hot spots and regional selective vulnerability for these disorders. The pattern of hippocampal AD-related tau pathology is strongly influenced by concomitant AGD. Mathematical analysis reveals that hippocampal involvement in primary tauopathies is distinguishable from early-stage AD-related neurofibrillary degeneration. Conclusion: Our data demonstrate disease-specific AT8 immunoreactivity patterns and hot spots in the hippocampus even in tauopathies, which primarily do not affect the hippocampus. These hot spots can be shifted to other regions by the co-occurrence of tauopathies like AGD. Our observations support the notion that globular glial tauopathies and tau-astrogliopathy of the elderly are distinct entities.' acknowledgement: This study was supported by the European Commission’s 7th Framework Programme under GA No. 278486, ‘DEVELAGE’. article_processing_charge: No article_type: original author: - first_name: Ivan full_name: Milenković, Ivan last_name: Milenković - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 - first_name: Gábor full_name: Kovács, Gábor last_name: Kovács citation: ama: Milenković I, Petrov T, Kovács G. Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders. 2014;38(5-6):375-388. doi:10.1159/000365548 apa: Milenković, I., Petrov, T., & Kovács, G. (2014). Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders. Karger Publishers. https://doi.org/10.1159/000365548 chicago: Milenković, Ivan, Tatjana Petrov, and Gábor Kovács. “Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias.” Dementia and Geriatric Cognitive Disorders. Karger Publishers, 2014. https://doi.org/10.1159/000365548. ieee: I. Milenković, T. Petrov, and G. Kovács, “Patterns of hippocampal tau pathology differentiate neurodegenerative dementias,” Dementia and Geriatric Cognitive Disorders, vol. 38, no. 5–6. Karger Publishers, pp. 375–388, 2014. ista: Milenković I, Petrov T, Kovács G. 2014. Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders. 38(5–6), 375–388. mla: Milenković, Ivan, et al. “Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias.” Dementia and Geriatric Cognitive Disorders, vol. 38, no. 5–6, Karger Publishers, 2014, pp. 375–88, doi:10.1159/000365548. short: I. Milenković, T. Petrov, G. Kovács, Dementia and Geriatric Cognitive Disorders 38 (2014) 375–388. date_created: 2018-12-11T11:54:41Z date_published: 2014-11-07T00:00:00Z date_updated: 2023-10-17T10:21:17Z day: '07' department: - _id: CaGu doi: 10.1159/000365548 external_id: pmid: - '25195847' intvolume: ' 38' issue: 5-6 language: - iso: eng main_file_link: - open_access: '1' url: https://kops.uni-konstanz.de/bitstream/123456789/42127/1/Milenkovic_2-17ivylo2up0798.pdf month: '11' oa: 1 oa_version: Published Version page: 375 - 388 pmid: 1 publication: Dementia and Geriatric Cognitive Disorders publication_identifier: issn: - 1420-8008 publication_status: published publisher: Karger Publishers publist_id: '5181' quality_controlled: '1' scopus_import: '1' status: public title: Patterns of hippocampal tau pathology differentiate neurodegenerative dementias type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 38 year: '2014' ... --- _id: '3168' abstract: - lang: eng text: The induction of a signaling pathway is characterized by transient complex formation and mutual posttranslational modification of proteins. To faithfully capture this combinatorial process in a mathematical model is an important challenge in systems biology. Exploiting the limited context on which most binding and modification events are conditioned, attempts have been made to reduce the combinatorial complexity by quotienting the reachable set of molecular species into species aggregates while preserving the deterministic semantics of the thermodynamic limit. Recently, we proposed a quotienting that also preserves the stochastic semantics and that is complete in the sense that the semantics of individual species can be recovered from the aggregate semantics. In this paper, we prove that this quotienting yields a sufficient condition for weak lumpability (that is to say that the quotient system is still Markovian for a given set of initial distributions) and that it gives rise to a backward Markov bisimulation between the original and aggregated transition system (which means that the conditional probability of being in a given state in the original system knowing that we are in its equivalence class is an invariant of the system). We illustrate the framework on a case study of the epidermal growth factor (EGF)/insulin receptor crosstalk. acknowledgement: "We would like to thank the anonymous reviewers for their comments on the different versions of the paper. We would also like to thank Ferdinanda Camporesi for her careful reading and the useful insights that she gave us about the paper.\r\nJérôme Feret’s contribution was partially supported by the AbstractCell ANR-Chair of Excellence. Heinz Koeppl’s research is supported by the Swiss National Science Foundation, grant no. 200020-117975/1. Tatjana Petrov’s research is supported by SystemsX.ch (the Swiss Initiative in Systems Biology)." author: - first_name: Jérôme full_name: Feret, Jérôme last_name: Feret - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Heinz full_name: Koeppl, Heinz last_name: Koeppl - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: Feret J, Henzinger TA, Koeppl H, Petrov T. Lumpability abstractions of rule based systems. Theoretical Computer Science. 2012;431:137-164. doi:10.1016/j.tcs.2011.12.059 apa: Feret, J., Henzinger, T. A., Koeppl, H., & Petrov, T. (2012). Lumpability abstractions of rule based systems. Theoretical Computer Science. Elsevier. https://doi.org/10.1016/j.tcs.2011.12.059 chicago: Feret, Jérôme, Thomas A Henzinger, Heinz Koeppl, and Tatjana Petrov. “Lumpability Abstractions of Rule Based Systems.” Theoretical Computer Science. Elsevier, 2012. https://doi.org/10.1016/j.tcs.2011.12.059. ieee: J. Feret, T. A. Henzinger, H. Koeppl, and T. Petrov, “Lumpability abstractions of rule based systems,” Theoretical Computer Science, vol. 431. Elsevier, pp. 137–164, 2012. ista: Feret J, Henzinger TA, Koeppl H, Petrov T. 2012. Lumpability abstractions of rule based systems. Theoretical Computer Science. 431, 137–164. mla: Feret, Jérôme, et al. “Lumpability Abstractions of Rule Based Systems.” Theoretical Computer Science, vol. 431, Elsevier, 2012, pp. 137–64, doi:10.1016/j.tcs.2011.12.059. short: J. Feret, T.A. Henzinger, H. Koeppl, T. Petrov, Theoretical Computer Science 431 (2012) 137–164. date_created: 2018-12-11T12:01:47Z date_published: 2012-05-04T00:00:00Z date_updated: 2023-02-23T11:39:40Z day: '04' department: - _id: ToHe doi: 10.1016/j.tcs.2011.12.059 intvolume: ' 431' language: - iso: eng month: '05' oa_version: None page: 137 - 164 publication: Theoretical Computer Science publication_status: published publisher: Elsevier publist_id: '3515' pubrep_id: '73' quality_controlled: '1' related_material: record: - id: '3719' relation: earlier_version status: public scopus_import: 1 status: public title: Lumpability abstractions of rule based systems type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 431 year: '2012' ... --- _id: '3719' abstract: - lang: eng text: The induction of a signaling pathway is characterized by transient complex formation and mutual posttranslational modification of proteins. To faithfully capture this combinatorial process in a math- ematical model is an important challenge in systems biology. Exploiting the limited context on which most binding and modification events are conditioned, attempts have been made to reduce the com- binatorial complexity by quotienting the reachable set of molecular species, into species aggregates while preserving the deterministic semantics of the thermodynamic limit. Recently we proposed a quotienting that also preserves the stochastic semantics and that is complete in the sense that the semantics of individual species can be recovered from the aggregate semantics. In this paper we prove that this quotienting yields a sufficient condition for weak lumpability and that it gives rise to a backward Markov bisimulation between the original and aggregated transition system. We illustrate the framework on a case study of the EGF/insulin receptor crosstalk. acknowledgement: Jérôme Feret’s contribution was partially supported by the ABSTRACTCELL ANR-Chair of Excellence. Heinz Koeppl acknowledges the support from the Swiss National Science Foundation, grant no. 200020-117975/1. Tatjana Petrov acknowledges the support from SystemsX.ch, the Swiss Initiative in Systems Biology. alternative_title: - EPTCS author: - first_name: Jérôme full_name: Feret, Jérôme last_name: Feret - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Heinz full_name: Koeppl, Heinz last_name: Koeppl - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: 'Feret J, Henzinger TA, Koeppl H, Petrov T. Lumpability abstractions of rule-based systems. In: Vol 40. Open Publishing Association; 2010:142-161.' apa: 'Feret, J., Henzinger, T. A., Koeppl, H., & Petrov, T. (2010). Lumpability abstractions of rule-based systems (Vol. 40, pp. 142–161). Presented at the MECBIC: Membrane Computing and Biologically Inspired Process Calculi, Jena, Germany: Open Publishing Association.' chicago: Feret, Jérôme, Thomas A Henzinger, Heinz Koeppl, and Tatjana Petrov. “Lumpability Abstractions of Rule-Based Systems,” 40:142–61. Open Publishing Association, 2010. ieee: 'J. Feret, T. A. Henzinger, H. Koeppl, and T. Petrov, “Lumpability abstractions of rule-based systems,” presented at the MECBIC: Membrane Computing and Biologically Inspired Process Calculi, Jena, Germany, 2010, vol. 40, pp. 142–161.' ista: 'Feret J, Henzinger TA, Koeppl H, Petrov T. 2010. Lumpability abstractions of rule-based systems. MECBIC: Membrane Computing and Biologically Inspired Process Calculi, EPTCS, vol. 40, 142–161.' mla: Feret, Jérôme, et al. Lumpability Abstractions of Rule-Based Systems. Vol. 40, Open Publishing Association, 2010, pp. 142–61. short: J. Feret, T.A. Henzinger, H. Koeppl, T. Petrov, in:, Open Publishing Association, 2010, pp. 142–161. conference: end_date: 2010-08-23 location: Jena, Germany name: 'MECBIC: Membrane Computing and Biologically Inspired Process Calculi' start_date: 2010-08-23 date_created: 2018-12-11T12:04:47Z date_published: 2010-10-30T00:00:00Z date_updated: 2023-02-23T11:15:19Z day: '30' ddc: - '570' department: - _id: ToHe - _id: CaGu external_id: arxiv: - '1011.0496' file: - access_level: open_access checksum: eaaba991a86fff37606b0eb5196878e8 content_type: application/pdf creator: kschuh date_created: 2019-01-31T12:09:09Z date_updated: 2020-07-14T12:46:14Z file_id: '5904' file_name: Lumpability_abstractions_of_rule-based_systems.pdf file_size: 907155 relation: main_file file_date_updated: 2020-07-14T12:46:14Z has_accepted_license: '1' intvolume: ' 40' language: - iso: eng month: '10' oa: 1 oa_version: Submitted Version page: 142-161 publication_status: published publisher: Open Publishing Association publist_id: '2511' quality_controlled: '1' related_material: record: - id: '3168' relation: later_version status: public scopus_import: 1 status: public title: Lumpability abstractions of rule-based systems type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 40 year: '2010' ... --- _id: '4533' abstract: - lang: eng text: Interface theories have been proposed to support incremental design and independent implementability. Incremental design means that the compatibility checking of interfaces can proceed for partial system descriptions, without knowing the interfaces of all components. Independent implementability means that compatible interfaces can be refined separately, maintaining compatibility. We show that these interface theories provide no formal support for component reuse, meaning that the same component cannot be used to implement several different interfaces in a design. We add a new operation to interface theories in order to support such reuse. For example, different interfaces for the same component may refer to different aspects such as functionality, timing, and power consumption. We give both stateless and stateful examples for interface theories with component reuse. To illustrate component reuse in interface-based design, we show how the stateful theory provides a natural framework for specifying and refining PCI bus clients. author: - first_name: Laurent full_name: Doyen, Laurent last_name: Doyen - first_name: Thomas A full_name: Thomas Henzinger id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Barbara full_name: Jobstmann, Barbara last_name: Jobstmann - first_name: Tatjana full_name: Tatjana Petrov id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: 'Doyen L, Henzinger TA, Jobstmann B, Petrov T. Interface theories with component reuse. In: ACM; 2008:79-88. doi:10.1145/1450058.1450070' apa: 'Doyen, L., Henzinger, T. A., Jobstmann, B., & Petrov, T. (2008). Interface theories with component reuse (pp. 79–88). Presented at the EMSOFT: Embedded Software , ACM. https://doi.org/10.1145/1450058.1450070' chicago: Doyen, Laurent, Thomas A Henzinger, Barbara Jobstmann, and Tatjana Petrov. “Interface Theories with Component Reuse,” 79–88. ACM, 2008. https://doi.org/10.1145/1450058.1450070. ieee: 'L. Doyen, T. A. Henzinger, B. Jobstmann, and T. Petrov, “Interface theories with component reuse,” presented at the EMSOFT: Embedded Software , 2008, pp. 79–88.' ista: 'Doyen L, Henzinger TA, Jobstmann B, Petrov T. 2008. Interface theories with component reuse. EMSOFT: Embedded Software , 79–88.' mla: Doyen, Laurent, et al. Interface Theories with Component Reuse. ACM, 2008, pp. 79–88, doi:10.1145/1450058.1450070. short: L. Doyen, T.A. Henzinger, B. Jobstmann, T. Petrov, in:, ACM, 2008, pp. 79–88. conference: name: 'EMSOFT: Embedded Software ' date_created: 2018-12-11T12:09:21Z date_published: 2008-10-01T00:00:00Z date_updated: 2021-01-12T07:59:30Z day: '01' doi: 10.1145/1450058.1450070 extern: 1 main_file_link: - open_access: '0' url: http://pub.ist.ac.at/%7Etah/Publications/interface_theories_with_component_reuse.pdf month: '10' page: 79 - 88 publication_status: published publisher: ACM publist_id: '193' quality_controlled: 0 status: public title: Interface theories with component reuse type: conference year: '2008' ...