--- _id: '9851' abstract: - lang: eng text: Based on the intuitive derivation of the dynamics of SIM allele frequency pM in the main text, we present a heuristic prediction for the long-term SIM allele frequencies with χ > 1 stresses and compare it to numerical simulations. article_processing_charge: No author: - first_name: Marta full_name: Lukacisinova, Marta id: 4342E402-F248-11E8-B48F-1D18A9856A87 last_name: Lukacisinova orcid: 0000-0002-2519-8004 - first_name: Sebastian full_name: Novak, Sebastian id: 461468AE-F248-11E8-B48F-1D18A9856A87 last_name: Novak - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 citation: ama: Lukacisinova M, Novak S, Paixao T. Heuristic prediction for multiple stresses. 2017. doi:10.1371/journal.pcbi.1005609.s003 apa: Lukacisinova, M., Novak, S., & Paixao, T. (2017). Heuristic prediction for multiple stresses. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s003 chicago: Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Heuristic Prediction for Multiple Stresses.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s003. ieee: M. Lukacisinova, S. Novak, and T. Paixao, “Heuristic prediction for multiple stresses.” Public Library of Science, 2017. ista: Lukacisinova M, Novak S, Paixao T. 2017. Heuristic prediction for multiple stresses, Public Library of Science, 10.1371/journal.pcbi.1005609.s003. mla: Lukacisinova, Marta, et al. Heuristic Prediction for Multiple Stresses. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s003. short: M. Lukacisinova, S. Novak, T. Paixao, (2017). date_created: 2021-08-09T14:08:14Z date_published: 2017-07-18T00:00:00Z date_updated: 2023-02-23T12:55:39Z day: '18' department: - _id: ToBo - _id: CaGu - _id: NiBa doi: 10.1371/journal.pcbi.1005609.s003 month: '07' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '696' relation: used_in_publication status: public status: public title: Heuristic prediction for multiple stresses type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9852' abstract: - lang: eng text: We show how different combination strategies affect the fraction of individuals that are multi-resistant. article_processing_charge: No author: - first_name: Marta full_name: Lukacisinova, Marta id: 4342E402-F248-11E8-B48F-1D18A9856A87 last_name: Lukacisinova orcid: 0000-0002-2519-8004 - first_name: Sebastian full_name: Novak, Sebastian id: 461468AE-F248-11E8-B48F-1D18A9856A87 last_name: Novak - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 citation: ama: Lukacisinova M, Novak S, Paixao T. Resistance frequencies for different combination strategies. 2017. doi:10.1371/journal.pcbi.1005609.s004 apa: Lukacisinova, M., Novak, S., & Paixao, T. (2017). Resistance frequencies for different combination strategies. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s004 chicago: Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Resistance Frequencies for Different Combination Strategies.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s004. ieee: M. Lukacisinova, S. Novak, and T. Paixao, “Resistance frequencies for different combination strategies.” Public Library of Science, 2017. ista: Lukacisinova M, Novak S, Paixao T. 2017. Resistance frequencies for different combination strategies, Public Library of Science, 10.1371/journal.pcbi.1005609.s004. mla: Lukacisinova, Marta, et al. Resistance Frequencies for Different Combination Strategies. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s004. short: M. Lukacisinova, S. Novak, T. Paixao, (2017). date_created: 2021-08-09T14:11:40Z date_published: 2017-07-18T00:00:00Z date_updated: 2023-02-23T12:55:39Z day: '18' department: - _id: ToBo - _id: CaGu - _id: NiBa doi: 10.1371/journal.pcbi.1005609.s004 month: '07' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '696' relation: used_in_publication status: public status: public title: Resistance frequencies for different combination strategies type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9844' article_processing_charge: No author: - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 - first_name: Frank full_name: Schreiber, Frank last_name: Schreiber - first_name: Alma full_name: Dal Co, Alma last_name: Dal Co - first_name: Daniel full_name: Kiviet, Daniel last_name: Kiviet - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Sten full_name: Littmann, Sten last_name: Littmann - first_name: Marcel full_name: Kuypers, Marcel last_name: Kuypers - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Nikolic N, Schreiber F, Dal Co A, et al. Source data for figures and tables. 2017. doi:10.1371/journal.pgen.1007122.s018 apa: Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Source data for figures and tables. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122.s018 chicago: Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Source Data for Figures and Tables.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.s018. ieee: N. Nikolic et al., “Source data for figures and tables.” Public Library of Science, 2017. ista: Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Source data for figures and tables, Public Library of Science, 10.1371/journal.pgen.1007122.s018. mla: Nikolic, Nela, et al. Source Data for Figures and Tables. Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122.s018. short: N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, (2017). date_created: 2021-08-09T13:27:16Z date_published: 2017-12-18T00:00:00Z date_updated: 2023-02-23T12:25:04Z day: '18' department: - _id: CaGu doi: 10.1371/journal.pgen.1007122.s018 month: '12' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '541' relation: used_in_publication status: public status: public title: Source data for figures and tables type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '561' abstract: - lang: eng text: Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape. acknowledgement: This work was funded by an HFSP Young Investigators' grant RGY0079/2011 (C.C.G.). M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria. article_number: '20170646' article_processing_charge: No article_type: original author: - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 2017;13(12). doi:10.1098/rsbl.2017.0646 apa: Pleska, M., & Guet, C. C. (2017). Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. The Royal Society. https://doi.org/10.1098/rsbl.2017.0646 chicago: Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” Biology Letters. The Royal Society, 2017. https://doi.org/10.1098/rsbl.2017.0646. ieee: M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites during escape from restriction–modification,” Biology Letters, vol. 13, no. 12. The Royal Society, 2017. ista: Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 13(12), 20170646. mla: Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” Biology Letters, vol. 13, no. 12, 20170646, The Royal Society, 2017, doi:10.1098/rsbl.2017.0646. short: M. Pleska, C.C. Guet, Biology Letters 13 (2017). date_created: 2018-12-11T11:47:11Z date_published: 2017-12-01T00:00:00Z date_updated: 2023-09-07T11:59:32Z day: '01' department: - _id: CaGu doi: 10.1098/rsbl.2017.0646 external_id: pmid: - '29237814' intvolume: ' 13' issue: '12' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1098/rsbl.2017.0646 month: '12' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 251BCBEC-B435-11E9-9278-68D0E5697425 grant_number: RGY0079/2011 name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant) - _id: 251D65D8-B435-11E9-9278-68D0E5697425 grant_number: '24210' name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship) publication: Biology Letters publication_identifier: issn: - 1744-9561 publication_status: published publisher: The Royal Society publist_id: '7253' quality_controlled: '1' related_material: record: - id: '9847' relation: research_data status: public - id: '202' relation: dissertation_contains status: public scopus_import: '1' status: public title: Effects of mutations in phage restriction sites during escape from restriction–modification type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2017' ... --- _id: '202' abstract: - lang: eng text: 'Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.' acknowledgement: "During my PhD studies, I received help from many people, all of which unfortunately cannot be listed here. I thank them deeply and hope that I never made them regret their kindness.\r\nI would like to express my deepest gratitude to Călin Guet, who went far beyond his responsibilities as an advisor and was to me also a great mentor and a friend. Călin never questioned my potential or lacked compassion and I cannot thank him enough for cultivating in me an independent scientist. I was amazed by his ability to recognize the most fascinating scientific problems in objects of study that others would find mundane. I hope I adopted at least a fraction of this ability.\r\nI will be forever grateful to Bruce Levin for all his support and especially for giving me the best possible example of how one can practice excellent science with humor and style. Working with Bruce was a true privilege.\r\nI thank Jonathan Bollback and Gašper Tkačik for serving in my PhD committee and the Austrian Academy of Science for funding my PhD research via the DOC fellowship.\r\nI thank all our lab members: Tobias Bergmiller for his guidance, especially in the first years of my research, and for being a good friend throughout; Remy Chait for staying in the lab at unreasonable hours and for the good laughs at bad jokes we shared; Anna Staron for supportively listening to my whines whenever I had to run a gel; Magdalena Steinrück for her pioneering work in the lab; Kathrin Tomasek for keeping the entropic forces in check and for her FACS virtuosity; Isabella Tomanek for always being nice to me, no matter how much bench space I took from her.\r\nI thank all my collaborators: Reiko Okura and Yuichi Wakamoto for performing and analyzing the microfluidic experiments; Long Qian and Edo Kussell for their bioinformatics analysis; Dominik Refardt for the λ kan phage; Moritz for his help with the mathematical modeling. I thank Fabienne Jesse for her tireless editorial work on all our manuscripts.\r\nFinally, I would like to thank my family and especially my wife Edita, who sacrificed a lot so that I can pursue my goals and dreams.\r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 citation: ama: Pleska M. Biology of restriction-modification systems at the single-cell and population level. 2017. doi:10.15479/AT:ISTA:th_916 apa: Pleska, M. (2017). Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_916 chicago: Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell and Population Level.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_916. ieee: M. Pleska, “Biology of restriction-modification systems at the single-cell and population level,” Institute of Science and Technology Austria, 2017. ista: Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria. mla: Pleska, Maros. Biology of Restriction-Modification Systems at the Single-Cell and Population Level. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:th_916. short: M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, Institute of Science and Technology Austria, 2017. date_created: 2018-12-11T11:45:10Z date_published: 2017-10-01T00:00:00Z date_updated: 2023-09-15T12:04:56Z day: '01' ddc: - '576' - '579' degree_awarded: PhD department: - _id: CaGu doi: 10.15479/AT:ISTA:th_916 file: - access_level: open_access checksum: 33cfb59674e91f82e3738396d3fb3776 content_type: application/pdf creator: system date_created: 2018-12-12T10:08:48Z date_updated: 2020-07-14T12:45:24Z file_id: '4710' file_name: IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf file_size: 18569590 relation: main_file - access_level: closed checksum: dcc239968decb233e7f98cf1083d8c26 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2019-04-05T08:33:14Z date_updated: 2020-07-14T12:45:24Z file_id: '6204' file_name: 2017_Pleska_Maros_Thesis.docx file_size: 2801649 relation: source_file file_date_updated: 2020-07-14T12:45:24Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '10' oa: 1 oa_version: Published Version page: '126' project: - _id: 251D65D8-B435-11E9-9278-68D0E5697425 grant_number: '24210' name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship) publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '7711' pubrep_id: '916' related_material: record: - id: '1243' relation: part_of_dissertation status: public - id: '561' relation: part_of_dissertation status: public - id: '457' relation: part_of_dissertation status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 title: Biology of restriction-modification systems at the single-cell and population level 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: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 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: '1336' abstract: - lang: eng text: Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse the runtimes of EAs on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient. article_processing_charge: No author: - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Jorge full_name: Pérez Heredia, Jorge last_name: Pérez Heredia - first_name: Dirk full_name: Sudholt, Dirk last_name: Sudholt - first_name: Barbora full_name: Trubenova, Barbora id: 42302D54-F248-11E8-B48F-1D18A9856A87 last_name: Trubenova orcid: 0000-0002-6873-2967 citation: ama: Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 2017;78(2):681-713. doi:10.1007/s00453-016-0212-1 apa: Paixao, T., Pérez Heredia, J., Sudholt, D., & Trubenova, B. (2017). Towards a runtime comparison of natural and artificial evolution. Algorithmica. Springer. https://doi.org/10.1007/s00453-016-0212-1 chicago: Paixao, Tiago, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica. Springer, 2017. https://doi.org/10.1007/s00453-016-0212-1. ieee: T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “Towards a runtime comparison of natural and artificial evolution,” Algorithmica, vol. 78, no. 2. Springer, pp. 681–713, 2017. ista: Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2017. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 78(2), 681–713. mla: Paixao, Tiago, et al. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica, vol. 78, no. 2, Springer, 2017, pp. 681–713, doi:10.1007/s00453-016-0212-1. short: T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica 78 (2017) 681–713. date_created: 2018-12-11T11:51:27Z date_published: 2017-06-01T00:00:00Z date_updated: 2023-09-20T11:14:42Z day: '01' ddc: - '576' department: - _id: NiBa - _id: CaGu doi: 10.1007/s00453-016-0212-1 ec_funded: 1 external_id: isi: - '000400379500013' file: - access_level: open_access checksum: 7873f665a0c598ac747c908f34cb14b9 content_type: application/pdf creator: system date_created: 2018-12-12T10:10:19Z date_updated: 2020-07-14T12:44:44Z file_id: '4805' file_name: IST-2016-658-v1+1_s00453-016-0212-1.pdf file_size: 710206 relation: main_file file_date_updated: 2020-07-14T12:44:44Z has_accepted_license: '1' intvolume: ' 78' isi: 1 issue: '2' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 681 - 713 project: - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation publication: Algorithmica publication_identifier: issn: - '01784617' publication_status: published publisher: Springer publist_id: '5931' pubrep_id: '658' quality_controlled: '1' scopus_import: '1' status: public title: Towards a runtime comparison of natural and artificial evolution 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: 78 year: '2017' ... --- _id: '1084' abstract: - lang: eng text: 'BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities.' article_processing_charge: No author: - first_name: Chong full_name: Fang, Chong last_name: Fang - first_name: Anna A full_name: Nagy-Staron, Anna A id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87 last_name: Nagy-Staron orcid: 0000-0002-1391-8377 - first_name: Martin full_name: Grafe, Martin last_name: Grafe - first_name: Ralf full_name: Heermann, Ralf last_name: Heermann - first_name: Kirsten full_name: Jung, Kirsten last_name: Jung - first_name: Susanne full_name: Gebhard, Susanne last_name: Gebhard - first_name: Thorsten full_name: Mascher, Thorsten last_name: Mascher citation: ama: Fang C, Nagy-Staron AA, Grafe M, et al. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 2017;104(1):16-31. doi:10.1111/mmi.13597 apa: Fang, C., Nagy-Staron, A. A., Grafe, M., Heermann, R., Jung, K., Gebhard, S., & Mascher, T. (2017). Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. Wiley-Blackwell. https://doi.org/10.1111/mmi.13597 chicago: Fang, Chong, Anna A Nagy-Staron, Martin Grafe, Ralf Heermann, Kirsten Jung, Susanne Gebhard, and Thorsten Mascher. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology. Wiley-Blackwell, 2017. https://doi.org/10.1111/mmi.13597. ieee: C. Fang et al., “Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis,” Molecular Microbiology, vol. 104, no. 1. Wiley-Blackwell, pp. 16–31, 2017. ista: Fang C, Nagy-Staron AA, Grafe M, Heermann R, Jung K, Gebhard S, Mascher T. 2017. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 104(1), 16–31. mla: Fang, Chong, et al. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology, vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:10.1111/mmi.13597. short: C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T. Mascher, Molecular Microbiology 104 (2017) 16–31. date_created: 2018-12-11T11:50:03Z date_published: 2017-04-01T00:00:00Z date_updated: 2023-09-20T11:48:43Z day: '01' department: - _id: CaGu doi: 10.1111/mmi.13597 external_id: isi: - '000398059200002' intvolume: ' 104' isi: 1 issue: '1' language: - iso: eng month: '04' oa_version: None page: 16 - 31 publication: Molecular Microbiology publication_identifier: issn: - ' 0950382X' publication_status: published publisher: Wiley-Blackwell publist_id: '6294' quality_controlled: '1' scopus_import: '1' status: public title: Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 104 year: '2017' ... --- _id: '954' abstract: - lang: eng text: Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for. article_number: e25192 article_processing_charge: Yes author: - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192 apa: Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192 chicago: Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192. ieee: M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the mechanistic nature of epistasis in a canonical cis-regulatory element,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192. mla: Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife, vol. 6, e25192, eLife Sciences Publications, 2017, doi:10.7554/eLife.25192. short: M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017). date_created: 2018-12-11T11:49:23Z date_published: 2017-05-18T00:00:00Z date_updated: 2023-09-22T10:01:17Z day: '18' ddc: - '576' department: - _id: CaGu - _id: NiBa - _id: JoBo doi: 10.7554/eLife.25192 ec_funded: 1 external_id: isi: - '000404024800001' file: - access_level: open_access checksum: 59cdd4400fb41280122d414fea971546 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:49Z date_updated: 2020-07-14T12:48:16Z file_id: '5306' file_name: IST-2017-841-v1+1_elife-25192-v2.pdf file_size: 2441529 relation: main_file - access_level: open_access checksum: b69024880558b858eb8c5d47a92b6377 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:50Z date_updated: 2020-07-14T12:48:16Z file_id: '5307' file_name: IST-2017-841-v1+2_elife-25192-figures-v2.pdf file_size: 3752660 relation: main_file file_date_updated: 2020-07-14T12:48:16Z has_accepted_license: '1' intvolume: ' 6' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _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: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer publication: eLife publication_identifier: issn: - 2050084X publication_status: published publisher: eLife Sciences Publications publist_id: '6460' pubrep_id: '841' quality_controlled: '1' scopus_import: '1' status: public title: On the mechanistic nature of epistasis in a canonical cis-regulatory element 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: 6 year: '2017' ... --- _id: '1007' abstract: - lang: eng text: 'A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.' article_processing_charge: Yes (in subscription journal) author: - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Eduardo full_name: Sontag, Eduardo last_name: Sontag citation: ama: Lang M, Sontag E. Zeros of nonlinear systems with input invariances. Automatica. 2017;81C:46-55. doi:10.1016/j.automatica.2017.03.030 apa: Lang, M., & Sontag, E. (2017). Zeros of nonlinear systems with input invariances. Automatica. International Federation of Automatic Control. https://doi.org/10.1016/j.automatica.2017.03.030 chicago: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica. International Federation of Automatic Control, 2017. https://doi.org/10.1016/j.automatica.2017.03.030. ieee: M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,” Automatica, vol. 81C. International Federation of Automatic Control, pp. 46–55, 2017. ista: Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55. mla: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:10.1016/j.automatica.2017.03.030. short: M. Lang, E. Sontag, Automatica 81C (2017) 46–55. date_created: 2018-12-11T11:49:39Z date_published: 2017-06-01T00:00:00Z date_updated: 2023-10-17T08:51:18Z day: '01' ddc: - '000' department: - _id: CaGu - _id: GaTk doi: 10.1016/j.automatica.2017.03.030 ec_funded: 1 external_id: isi: - '000403513900006' file: - access_level: open_access content_type: application/pdf creator: system date_created: 2018-12-12T10:11:29Z date_updated: 2018-12-12T10:11:29Z file_id: '4884' file_name: IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf file_size: 1401954 relation: main_file file_date_updated: 2018-12-12T10:11:29Z has_accepted_license: '1' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 46 - 55 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Automatica publication_identifier: issn: - 0005-1098 publication_status: published publisher: International Federation of Automatic Control publist_id: '6391' pubrep_id: '813' quality_controlled: '1' scopus_import: '1' status: public title: Zeros of nonlinear systems with input invariances 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 81C year: '2017' ...