[{"volume":10,"doi":"10.1109/TCBB.2012.91","day":"03","abstract":[{"text":"We introduce propagation models (PMs), a formalism able to express several kinds of equations that describe the behavior of biochemical reaction networks. Furthermore, we introduce the propagation abstract data type (PADT), which separates concerns regarding different numerical algorithms for the transient analysis of biochemical reaction networks from concerns regarding their implementation, thus allowing for portable and efficient solutions. The state of a propagation abstract data type is given by a vector that assigns mass values to a set of nodes, and its (next) operator propagates mass values through this set of nodes. We propose an approximate implementation of the (next) operator, based on threshold abstraction, which propagates only &quot;significant&quot; mass values and thus achieves a compromise between efficiency and accuracy. Finally, we give three use cases for propagation models: the chemical master equation (CME), the reaction rate equation (RRE), and a hybrid method that combines these two equations. These three applications use propagation models in order to propagate probabilities and/or expected values and variances of the model's variables.","lang":"eng"}],"date_updated":"2021-01-12T06:56:38Z","year":"2012","citation":{"chicago":"Henzinger, Thomas A, and Maria Mateescu. “The Propagation Approach for Computing Biochemical Reaction Networks.” <i>IEEE ACM Transactions on Computational Biology and Bioinformatics</i>. IEEE, 2012. <a href=\"https://doi.org/10.1109/TCBB.2012.91\">https://doi.org/10.1109/TCBB.2012.91</a>.","ieee":"T. A. Henzinger and M. Mateescu, “The propagation approach for computing biochemical reaction networks,” <i>IEEE ACM Transactions on Computational Biology and Bioinformatics</i>, vol. 10, no. 2. IEEE, pp. 310–322, 2012.","ama":"Henzinger TA, Mateescu M. The propagation approach for computing biochemical reaction networks. <i>IEEE ACM Transactions on Computational Biology and Bioinformatics</i>. 2012;10(2):310-322. doi:<a href=\"https://doi.org/10.1109/TCBB.2012.91\">10.1109/TCBB.2012.91</a>","apa":"Henzinger, T. A., &#38; Mateescu, M. (2012). The propagation approach for computing biochemical reaction networks. <i>IEEE ACM Transactions on Computational Biology and Bioinformatics</i>. IEEE. <a href=\"https://doi.org/10.1109/TCBB.2012.91\">https://doi.org/10.1109/TCBB.2012.91</a>","ista":"Henzinger TA, Mateescu M. 2012. The propagation approach for computing biochemical reaction networks. IEEE ACM Transactions on Computational Biology and Bioinformatics. 10(2), 310–322.","short":"T.A. Henzinger, M. Mateescu, IEEE ACM Transactions on Computational Biology and Bioinformatics 10 (2012) 310–322.","mla":"Henzinger, Thomas A., and Maria Mateescu. “The Propagation Approach for Computing Biochemical Reaction Networks.” <i>IEEE ACM Transactions on Computational Biology and Bioinformatics</i>, vol. 10, no. 2, IEEE, 2012, pp. 310–22, doi:<a href=\"https://doi.org/10.1109/TCBB.2012.91\">10.1109/TCBB.2012.91</a>."},"external_id":{"pmid":["22778152"]},"publisher":"IEEE","page":"310 - 322","quality_controlled":"1","ec_funded":1,"publication_status":"published","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"date_created":"2018-12-11T11:56:52Z","title":"The propagation approach for computing biochemical reaction networks","intvolume":"        10","_id":"2302","pmid":1,"scopus_import":1,"author":[{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas A","last_name":"Henzinger","orcid":"0000−0002−2985−7724","full_name":"Henzinger, Thomas A"},{"id":"3B43276C-F248-11E8-B48F-1D18A9856A87","full_name":"Mateescu, Maria","first_name":"Maria","last_name":"Mateescu"}],"issue":"2","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publist_id":"4625","date_published":"2012-07-03T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"oa_version":"None","project":[{"call_identifier":"FP7","_id":"25EE3708-B435-11E9-9278-68D0E5697425","name":"Quantitative Reactive Modeling","grant_number":"267989"}],"month":"07","publication":"IEEE ACM Transactions on Computational Biology and Bioinformatics"},{"oa_version":"Published Version","month":"11","publication":"Biophysical Journal","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0006-3495"]},"oa":1,"type":"journal_article","date_published":"2011-11-16T00:00:00Z","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218319/","open_access":"1"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","date_created":"2019-05-28T11:54:29Z","article_processing_charge":"No","department":[{"_id":"CaGu"}],"publication_status":"published","intvolume":"       101","title":"Noise underlies switching behavior of the bacterial flagellum","scopus_import":"1","_id":"6496","pmid":1,"issue":"10","author":[{"last_name":"Park","first_name":"Heungwon","full_name":"Park, Heungwon"},{"full_name":"Oikonomou, Panos","last_name":"Oikonomou","first_name":"Panos"},{"first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Cluzel, Philippe","first_name":"Philippe","last_name":"Cluzel"}],"publisher":"Elsevier","quality_controlled":"1","page":"2336-2340","day":"16","doi":"10.1016/j.bpj.2011.09.040","abstract":[{"lang":"eng","text":"We report the switching behavior of the full bacterial flagellum system that includes the filament and the motor in wild-type Escherichia coli cells. In sorting the motor behavior by the clockwise bias, we find that the distributions of the clockwise (CW) and counterclockwise (CCW) intervals are either exponential or nonexponential with long tails. At low bias, CW intervals are exponentially distributed and CCW intervals exhibit long tails. At intermediate CW bias (0.5) both CW and CCW intervals are mainly exponentially distributed. A simple model suggests that these two distinct switching behaviors are governed by the presence of signaling noise within the chemotaxis network. Low noise yields exponentially distributed intervals, whereas large noise yields nonexponential behavior with long tails. These drastically different motor statistics may play a role in optimizing bacterial behavior for a wide range of environmental conditions."}],"citation":{"ista":"Park H, Oikonomou P, Guet CC, Cluzel P. 2011. Noise underlies switching behavior of the bacterial flagellum. Biophysical Journal. 101(10), 2336–2340.","mla":"Park, Heungwon, et al. “Noise Underlies Switching Behavior of the Bacterial Flagellum.” <i>Biophysical Journal</i>, vol. 101, no. 10, Elsevier, 2011, pp. 2336–40, doi:<a href=\"https://doi.org/10.1016/j.bpj.2011.09.040\">10.1016/j.bpj.2011.09.040</a>.","short":"H. Park, P. Oikonomou, C.C. Guet, P. Cluzel, Biophysical Journal 101 (2011) 2336–2340.","ieee":"H. Park, P. Oikonomou, C. C. Guet, and P. Cluzel, “Noise underlies switching behavior of the bacterial flagellum,” <i>Biophysical Journal</i>, vol. 101, no. 10. Elsevier, pp. 2336–2340, 2011.","chicago":"Park, Heungwon, Panos Oikonomou, Calin C Guet, and Philippe Cluzel. “Noise Underlies Switching Behavior of the Bacterial Flagellum.” <i>Biophysical Journal</i>. Elsevier, 2011. <a href=\"https://doi.org/10.1016/j.bpj.2011.09.040\">https://doi.org/10.1016/j.bpj.2011.09.040</a>.","ama":"Park H, Oikonomou P, Guet CC, Cluzel P. Noise underlies switching behavior of the bacterial flagellum. <i>Biophysical Journal</i>. 2011;101(10):2336-2340. doi:<a href=\"https://doi.org/10.1016/j.bpj.2011.09.040\">10.1016/j.bpj.2011.09.040</a>","apa":"Park, H., Oikonomou, P., Guet, C. C., &#38; Cluzel, P. (2011). Noise underlies switching behavior of the bacterial flagellum. <i>Biophysical Journal</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.bpj.2011.09.040\">https://doi.org/10.1016/j.bpj.2011.09.040</a>"},"year":"2011","date_updated":"2021-04-16T11:54:49Z","external_id":{"pmid":["22098731"]},"volume":101},{"author":[{"last_name":"Feret","first_name":"Jérôme","full_name":"Feret, Jérôme"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","full_name":"Henzinger, Thomas A","first_name":"Thomas A","last_name":"Henzinger"},{"full_name":"Koeppl, Heinz","first_name":"Heinz","last_name":"Koeppl"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","last_name":"Petrov","first_name":"Tatjana","full_name":"Petrov, Tatjana","orcid":"0000-0002-9041-0905"}],"scopus_import":1,"_id":"3719","intvolume":"        40","title":"Lumpability abstractions of rule-based systems","alternative_title":["EPTCS"],"date_created":"2018-12-11T12:04:47Z","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"publication_status":"published","file_date_updated":"2020-07-14T12:46:14Z","quality_controlled":"1","page":"142-161","publisher":"Open Publishing Association","external_id":{"arxiv":["1011.0496"]},"year":"2010","citation":{"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. <i>Lumpability Abstractions of Rule-Based Systems</i>. 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.","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.","chicago":"Feret, Jérôme, Thomas A Henzinger, Heinz Koeppl, and Tatjana Petrov. “Lumpability Abstractions of Rule-Based Systems,” 40:142–61. Open Publishing Association, 2010.","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., &#38; 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."},"date_updated":"2023-02-23T11:15:19Z","abstract":[{"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.","lang":"eng"}],"day":"30","arxiv":1,"ddc":["570"],"volume":40,"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.","has_accepted_license":"1","month":"10","oa_version":"Submitted Version","language":[{"iso":"eng"}],"conference":{"start_date":"2010-08-23","name":"MECBIC: Membrane Computing and Biologically Inspired Process Calculi","end_date":"2010-08-23","location":"Jena, Germany"},"type":"conference","date_published":"2010-10-30T00:00:00Z","publist_id":"2511","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","related_material":{"record":[{"id":"3168","relation":"later_version","status":"public"}]},"file":[{"relation":"main_file","access_level":"open_access","creator":"kschuh","file_id":"5904","checksum":"eaaba991a86fff37606b0eb5196878e8","file_size":907155,"date_created":"2019-01-31T12:09:09Z","content_type":"application/pdf","file_name":"Lumpability_abstractions_of_rule-based_systems.pdf","date_updated":"2020-07-14T12:46:14Z"}]},{"publisher":"IEEE","file_date_updated":"2020-07-14T12:46:17Z","page":"193 - 194","quality_controlled":"1","title":"SABRE: A tool for the stochastic analysis of biochemical reaction networks","pubrep_id":"63","publication_status":"published","date_created":"2018-12-11T12:05:29Z","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"author":[{"last_name":"Didier","first_name":"Frédéric","full_name":"Didier, Frédéric"},{"orcid":"0000−0002−2985−7724","full_name":"Henzinger, Thomas A","first_name":"Thomas A","last_name":"Henzinger","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Mateescu","first_name":"Maria","full_name":"Mateescu, Maria"},{"first_name":"Verena","last_name":"Wolf","full_name":"Wolf, Verena"}],"_id":"3847","scopus_import":1,"ddc":["004"],"abstract":[{"lang":"eng","text":"The importance of stochasticity within biological systems has been shown repeatedly during the last years and has raised the need for efficient stochastic tools. We present SABRE, a tool for stochastic analysis of biochemical reaction networks. SABRE implements fast adaptive uniformization (FAU), a direct numerical approximation algorithm for computing transient solutions of biochemical reaction networks. Biochemical reactions networks represent biological systems studied at a molecular level and these reactions can be modeled as transitions of a Markov chain. SABRE accepts as input the formalism of guarded commands, which it interprets either as continuous-time or as discrete-time Markov chains. Besides operating in a stochastic mode, SABRE may also perform a deterministic analysis by directly computing a mean-field approximation of the system under study. We illustrate the different functionalities of SABRE by means of biological case studies."}],"doi":"10.1109/QEST.2010.33","day":"14","date_updated":"2021-01-12T07:52:37Z","citation":{"ama":"Didier F, Henzinger TA, Mateescu M, Wolf V. SABRE: A tool for the stochastic analysis of biochemical reaction networks. In: IEEE; 2010:193-194. doi:<a href=\"https://doi.org/10.1109/QEST.2010.33\">10.1109/QEST.2010.33</a>","apa":"Didier, F., Henzinger, T. A., Mateescu, M., &#38; Wolf, V. (2010). SABRE: A tool for the stochastic analysis of biochemical reaction networks (pp. 193–194). Presented at the QEST: Quantitative Evaluation of Systems, Williamsburg, USA: IEEE. <a href=\"https://doi.org/10.1109/QEST.2010.33\">https://doi.org/10.1109/QEST.2010.33</a>","ieee":"F. Didier, T. A. Henzinger, M. Mateescu, and V. Wolf, “SABRE: A tool for the stochastic analysis of biochemical reaction networks,” presented at the QEST: Quantitative Evaluation of Systems, Williamsburg, USA, 2010, pp. 193–194.","chicago":"Didier, Frédéric, Thomas A Henzinger, Maria Mateescu, and Verena Wolf. “SABRE: A Tool for the Stochastic Analysis of Biochemical Reaction Networks,” 193–94. IEEE, 2010. <a href=\"https://doi.org/10.1109/QEST.2010.33\">https://doi.org/10.1109/QEST.2010.33</a>.","short":"F. Didier, T.A. Henzinger, M. Mateescu, V. Wolf, in:, IEEE, 2010, pp. 193–194.","mla":"Didier, Frédéric, et al. <i>SABRE: A Tool for the Stochastic Analysis of Biochemical Reaction Networks</i>. IEEE, 2010, pp. 193–94, doi:<a href=\"https://doi.org/10.1109/QEST.2010.33\">10.1109/QEST.2010.33</a>.","ista":"Didier F, Henzinger TA, Mateescu M, Wolf V. 2010. SABRE: A tool for the stochastic analysis of biochemical reaction networks. QEST: Quantitative Evaluation of Systems, 193–194."},"year":"2010","conference":{"name":"QEST: Quantitative Evaluation of Systems","start_date":"2010-09-15","end_date":"2010-09-18","location":"Williamsburg, USA"},"language":[{"iso":"eng"}],"month":"10","oa_version":"Submitted Version","has_accepted_license":"1","status":"public","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","file":[{"file_size":433824,"checksum":"38707b149d2174f01be406e794ffa849","date_created":"2018-12-12T10:09:03Z","file_name":"IST-2012-63-v1+1_SABRE-A_tool_for_the_stochastic_analysis_of_biochemical_reaction_networks.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:46:17Z","access_level":"open_access","relation":"main_file","creator":"system","file_id":"4726"}],"oa":1,"publist_id":"2339","date_published":"2010-10-14T00:00:00Z","type":"conference"},{"language":[{"iso":"eng"}],"conference":{"name":"HIBI: High-Performance Computational Systems Biology","start_date":"2009-10-14","location":"Trento, Italy","end_date":"2009-10-16"},"has_accepted_license":"1","month":"10","oa_version":"Submitted Version","related_material":{"record":[{"id":"3842","relation":"later_version","status":"public"}]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","file":[{"file_size":222890,"checksum":"9a3bde48f43203991a0b3c6a277c2f5b","date_created":"2020-05-19T16:33:55Z","content_type":"application/pdf","file_name":"2009_HIBI_Didier.pdf","date_updated":"2020-07-14T12:46:17Z","relation":"main_file","access_level":"open_access","creator":"dernst","file_id":"7874"}],"date_published":"2009-10-30T00:00:00Z","type":"conference","publist_id":"2348","oa":1,"file_date_updated":"2020-07-14T12:46:17Z","page":"118 - 127","quality_controlled":"1","publisher":"IEEE","author":[{"first_name":"Frédéric","last_name":"Didier","full_name":"Didier, Frédéric"},{"full_name":"Henzinger, Thomas A","orcid":"0000−0002−2985−7724","last_name":"Henzinger","first_name":"Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Mateescu","first_name":"Maria","full_name":"Mateescu, Maria","id":"3B43276C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Verena","last_name":"Wolf","full_name":"Wolf, Verena"}],"issue":"6","_id":"3843","scopus_import":1,"title":"Fast adaptive uniformization of the chemical master equation","intvolume":"         4","publication_status":"published","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"date_created":"2018-12-11T12:05:28Z","article_processing_charge":"No","ddc":["000"],"acknowledgement":"This research has been partially funded by the Swiss National Science Foundation under grant 205321-111840 and by the Cluster of Excellence on Multimodal Computing and Interaction at Saarland University.","volume":4,"date_updated":"2023-02-23T11:45:05Z","year":"2009","citation":{"short":"F. Didier, T.A. Henzinger, M. Mateescu, V. Wolf, in:, IEEE, 2009, pp. 118–127.","mla":"Didier, Frédéric, et al. <i>Fast Adaptive Uniformization of the Chemical Master Equation</i>. Vol. 4, no. 6, IEEE, 2009, pp. 118–27, doi:<a href=\"https://doi.org/10.1109/HiBi.2009.23\">10.1109/HiBi.2009.23</a>.","ista":"Didier F, Henzinger TA, Mateescu M, Wolf V. 2009. Fast adaptive uniformization of the chemical master equation. HIBI: High-Performance Computational Systems Biology vol. 4, 118–127.","ama":"Didier F, Henzinger TA, Mateescu M, Wolf V. Fast adaptive uniformization of the chemical master equation. In: Vol 4. IEEE; 2009:118-127. doi:<a href=\"https://doi.org/10.1109/HiBi.2009.23\">10.1109/HiBi.2009.23</a>","apa":"Didier, F., Henzinger, T. A., Mateescu, M., &#38; Wolf, V. (2009). Fast adaptive uniformization of the chemical master equation (Vol. 4, pp. 118–127). Presented at the HIBI: High-Performance Computational Systems Biology, Trento, Italy: IEEE. <a href=\"https://doi.org/10.1109/HiBi.2009.23\">https://doi.org/10.1109/HiBi.2009.23</a>","chicago":"Didier, Frédéric, Thomas A Henzinger, Maria Mateescu, and Verena Wolf. “Fast Adaptive Uniformization of the Chemical Master Equation,” 4:118–27. IEEE, 2009. <a href=\"https://doi.org/10.1109/HiBi.2009.23\">https://doi.org/10.1109/HiBi.2009.23</a>.","ieee":"F. Didier, T. A. Henzinger, M. Mateescu, and V. Wolf, “Fast adaptive uniformization of the chemical master equation,” presented at the HIBI: High-Performance Computational Systems Biology, Trento, Italy, 2009, vol. 4, no. 6, pp. 118–127."},"abstract":[{"text":"Within systems biology there is an increasing interest in the stochastic behavior of biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous- time Markov chain (CTMC).\r\nStandard Uniformization (SU) is an efficient method for the transient analysis of CTMCs. For systems with very different time scales, such as biochemical reaction networks, SU is computationally expensive. In these cases, a variant of SU, called adaptive uniformization (AU), is known to reduce the large number of iterations needed by SU. The additional difficulty of AU is that it requires the solution of a birth process.\r\nIn this paper we present an on-the-fly variant of AU, where we improve the original algorithm for AU at the cost of a small approximation error. By means of several examples, we show that our approach is particularly well-suited for biochemical reaction networks.","lang":"eng"}],"doi":"10.1109/HiBi.2009.23","day":"30"}]