--- _id: '1290' abstract: - lang: eng text: We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline. acknowledgement: "This work was supported in part by National Institute of Allergy and Infectious Diseases grant U54 AI057159, US National Institutes of Health grants R01 GM081617 (to R.K.) and GM086258 (to J.C.), European Research Council FP7 ERC grant 281891 (to R.K.) and a National Science Foundation Graduate Fellowship (to L.K.S.).\r\n" author: - first_name: Laura full_name: Stone, Laura last_name: Stone - first_name: Michael full_name: Baym, Michael last_name: Baym - first_name: Tami full_name: Lieberman, Tami last_name: Lieberman - first_name: Remy P full_name: Chait, Remy P id: 3464AE84-F248-11E8-B48F-1D18A9856A87 last_name: Chait orcid: 0000-0003-0876-3187 - first_name: Jon full_name: Clardy, Jon last_name: Clardy - first_name: Roy full_name: Kishony, Roy last_name: Kishony citation: ama: Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 2016;12(11):902-904. doi:10.1038/nchembio.2176 apa: Stone, L., Baym, M., Lieberman, T., Chait, R. P., Clardy, J., & Kishony, R. (2016). Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/nchembio.2176 chicago: Stone, Laura, Michael Baym, Tami Lieberman, Remy P Chait, Jon Clardy, and Roy Kishony. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/nchembio.2176. ieee: L. Stone, M. Baym, T. Lieberman, R. P. Chait, J. Clardy, and R. Kishony, “Compounds that select against the tetracycline-resistance efflux pump,” Nature Chemical Biology, vol. 12, no. 11. Nature Publishing Group, pp. 902–904, 2016. ista: Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. 2016. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 12(11), 902–904. mla: Stone, Laura, et al. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology, vol. 12, no. 11, Nature Publishing Group, 2016, pp. 902–04, doi:10.1038/nchembio.2176. short: L. Stone, M. Baym, T. Lieberman, R.P. Chait, J. Clardy, R. Kishony, Nature Chemical Biology 12 (2016) 902–904. date_created: 2018-12-11T11:51:10Z date_published: 2016-11-01T00:00:00Z date_updated: 2021-01-12T06:49:39Z day: '01' department: - _id: CaGu - _id: GaTk doi: 10.1038/nchembio.2176 intvolume: ' 12' issue: '11' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069154/ month: '11' oa: 1 oa_version: Preprint page: 902 - 904 publication: Nature Chemical Biology publication_status: published publisher: Nature Publishing Group publist_id: '6026' quality_controlled: '1' scopus_import: 1 status: public title: Compounds that select against the tetracycline-resistance efflux pump type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 12 year: '2016' ... --- _id: '1320' abstract: - lang: eng text: 'In recent years, several biomolecular systems have been shown to be scale-invariant (SI), i.e. to show the same output dynamics when exposed to geometrically scaled input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant inputs. In this article, we show that SI systems-as well as systems invariant with respect to other input transformations-can realize nonlinear differential operators: when excited by inputs obeying functional forms characteristic for a given class of invariant systems, the systems'' outputs converge to constant values directly quantifying the speed of the input.' acknowledgement: The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° [291734]. Work supported in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473. article_number: '7526722' 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. Scale-invariant systems realize nonlinear differential operators. In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722' apa: 'Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear differential operators (Vol. 2016–July). Presented at the ACC: American Control Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722' chicago: Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722. ieee: 'M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential operators,” presented at the ACC: American Control Conference, Boston, MA, USA, 2016, vol. 2016–July.' ista: 'Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential operators. ACC: American Control Conference vol. 2016–July, 7526722.' mla: Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722. short: M. Lang, E. Sontag, in:, IEEE, 2016. conference: end_date: 2016-07-08 location: Boston, MA, USA name: 'ACC: American Control Conference' start_date: 2016-07-06 date_created: 2018-12-11T11:51:21Z date_published: 2016-07-28T00:00:00Z date_updated: 2021-01-12T06:49:51Z day: '28' ddc: - '003' - '621' department: - _id: CaGu - _id: GaTk doi: 10.1109/ACC.2016.7526722 ec_funded: 1 file: - access_level: local checksum: 7219432b43defc62a0d45f48d4ce6a19 content_type: application/pdf creator: system date_created: 2018-12-12T10:16:17Z date_updated: 2020-07-14T12:44:43Z file_id: '5203' file_name: IST-2017-810-v1+1_root.pdf file_size: 539166 relation: main_file file_date_updated: 2020-07-14T12:44:43Z has_accepted_license: '1' language: - iso: eng month: '07' oa_version: Preprint project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication_status: published publisher: IEEE publist_id: '5950' pubrep_id: '810' quality_controlled: '1' scopus_import: 1 status: public title: Scale-invariant systems realize nonlinear differential operators type: conference user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 2016-July year: '2016' ... --- _id: '1332' abstract: - lang: eng text: Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance. acknowledgement: This work was partially supported by US National Institutes of Health grant R01-GM081617, Israeli Centers of Research Excellence I-CORE Program ISF Grant No. 152/11, and the European Research Council FP7 ERC Grant 281891. article_number: '10333' author: - first_name: Remy P full_name: Chait, Remy P id: 3464AE84-F248-11E8-B48F-1D18A9856A87 last_name: Chait orcid: 0000-0003-0876-3187 - first_name: Adam full_name: Palmer, Adam last_name: Palmer - first_name: Idan full_name: Yelin, Idan last_name: Yelin - first_name: Roy full_name: Kishony, Roy last_name: Kishony citation: ama: Chait RP, Palmer A, Yelin I, Kishony R. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 2016;7. doi:10.1038/ncomms10333 apa: Chait, R. P., Palmer, A., Yelin, I., & Kishony, R. (2016). Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms10333 chicago: Chait, Remy P, Adam Palmer, Idan Yelin, and Roy Kishony. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms10333. ieee: R. P. Chait, A. Palmer, I. Yelin, and R. Kishony, “Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments,” Nature Communications, vol. 7. Nature Publishing Group, 2016. ista: Chait RP, Palmer A, Yelin I, Kishony R. 2016. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 7, 10333. mla: Chait, Remy P., et al. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications, vol. 7, 10333, Nature Publishing Group, 2016, doi:10.1038/ncomms10333. short: R.P. Chait, A. Palmer, I. Yelin, R. Kishony, Nature Communications 7 (2016). date_created: 2018-12-11T11:51:25Z date_published: 2016-01-20T00:00:00Z date_updated: 2021-01-12T06:49:57Z day: '20' ddc: - '570' - '579' department: - _id: CaGu - _id: GaTk doi: 10.1038/ncomms10333 file: - access_level: open_access checksum: ef147bcbb8bd37e9079cf3ce06f5815d content_type: application/pdf creator: system date_created: 2018-12-12T10:13:52Z date_updated: 2020-07-14T12:44:44Z file_id: '5039' file_name: IST-2016-662-v1+1_ncomms10333.pdf file_size: 1844107 relation: main_file file_date_updated: 2020-07-14T12:44:44Z has_accepted_license: '1' intvolume: ' 7' language: - iso: eng month: '01' oa: 1 oa_version: Published Version publication: Nature Communications publication_status: published publisher: Nature Publishing Group publist_id: '5936' pubrep_id: '662' quality_controlled: '1' scopus_import: 1 status: public title: Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 7 year: '2016' ... --- _id: '1342' abstract: - lang: eng text: A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, the microbial evolution and growth arena (MEGA)-plate, in which bacteria spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation of mutation and selection in a migrating bacterial front.While resistance increased consistently, multiple coexisting lineages diversified both phenotypically and genotypically. Analyzing mutants at and behind the propagating front,we found that evolution is not always led by the most resistant mutants; highly resistant mutants may be trapped behindmore sensitive lineages.TheMEGA-plate provides a versatile platformfor studying microbial adaption and directly visualizing evolutionary dynamics. author: - first_name: Michael full_name: Baym, Michael last_name: Baym - first_name: Tami full_name: Lieberman, Tami last_name: Lieberman - first_name: Eric full_name: Kelsic, Eric last_name: Kelsic - first_name: Remy P full_name: Chait, Remy P id: 3464AE84-F248-11E8-B48F-1D18A9856A87 last_name: Chait orcid: 0000-0003-0876-3187 - first_name: Rotem full_name: Gross, Rotem last_name: Gross - first_name: Idan full_name: Yelin, Idan last_name: Yelin - first_name: Roy full_name: Kishony, Roy last_name: Kishony citation: ama: Baym M, Lieberman T, Kelsic E, et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 2016;353(6304):1147-1151. doi:10.1126/science.aag0822 apa: Baym, M., Lieberman, T., Kelsic, E., Chait, R. P., Gross, R., Yelin, I., & Kishony, R. (2016). Spatiotemporal microbial evolution on antibiotic landscapes. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aag0822 chicago: Baym, Michael, Tami Lieberman, Eric Kelsic, Remy P Chait, Rotem Gross, Idan Yelin, and Roy Kishony. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aag0822. ieee: M. Baym et al., “Spatiotemporal microbial evolution on antibiotic landscapes,” Science, vol. 353, no. 6304. American Association for the Advancement of Science, pp. 1147–1151, 2016. ista: Baym M, Lieberman T, Kelsic E, Chait RP, Gross R, Yelin I, Kishony R. 2016. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 353(6304), 1147–1151. mla: Baym, Michael, et al. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science, vol. 353, no. 6304, American Association for the Advancement of Science, 2016, pp. 1147–51, doi:10.1126/science.aag0822. short: M. Baym, T. Lieberman, E. Kelsic, R.P. Chait, R. Gross, I. Yelin, R. Kishony, Science 353 (2016) 1147–1151. date_created: 2018-12-11T11:51:29Z date_published: 2016-09-09T00:00:00Z date_updated: 2021-01-12T06:50:01Z day: '09' department: - _id: CaGu - _id: GaTk doi: 10.1126/science.aag0822 intvolume: ' 353' issue: '6304' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534434/ month: '09' oa: 1 oa_version: Preprint page: 1147 - 1151 publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '5911' quality_controlled: '1' scopus_import: 1 status: public title: Spatiotemporal microbial evolution on antibiotic landscapes type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 353 year: '2016' ... --- _id: '1349' abstract: - lang: eng text: Crossing fitness valleys is one of the major obstacles to function optimization. In this paper we investigate how the structure of the fitness valley, namely its depth d and length ℓ, influence the runtime of different strategies for crossing these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis algorithm. While the (1+1) EA has to jump across the valley to a point of higher fitness because it does not accept decreasing moves, the non-elitist algorithms may cross the valley by accepting worsening moves. We show that while the runtime of the (1+1) EA algorithm depends critically on the length of the valley, the runtimes of the non-elitist algorithms depend crucially only on the depth of the valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of small length. Moreover, we show that both SSWM and Metropolis can also efficiently optimize a rugged function consisting of consecutive valleys. author: - first_name: Pietro full_name: Oliveto, Pietro last_name: Oliveto - 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: Heredia, Jorge last_name: 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: 'Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. When non-elitism outperforms elitism for crossing fitness valleys. In: Proceedings of the Genetic and Evolutionary Computation Conference 2016 . ACM; 2016:1163-1170. doi:10.1145/2908812.2908909' apa: 'Oliveto, P., Paixao, T., Heredia, J., Sudholt, D., & Trubenova, B. (2016). When non-elitism outperforms elitism for crossing fitness valleys. In Proceedings of the Genetic and Evolutionary Computation Conference 2016 (pp. 1163–1170). Denver, CO, USA: ACM. https://doi.org/10.1145/2908812.2908909' chicago: Oliveto, Pietro, Tiago Paixao, Jorge Heredia, Dirk Sudholt, and Barbora Trubenova. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” In Proceedings of the Genetic and Evolutionary Computation Conference 2016 , 1163–70. ACM, 2016. https://doi.org/10.1145/2908812.2908909. ieee: P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, and B. Trubenova, “When non-elitism outperforms elitism for crossing fitness valleys,” in Proceedings of the Genetic and Evolutionary Computation Conference 2016 , Denver, CO, USA, 2016, pp. 1163–1170. ista: 'Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. 2016. When non-elitism outperforms elitism for crossing fitness valleys. Proceedings of the Genetic and Evolutionary Computation Conference 2016 . GECCO: Genetic and evolutionary computation conference, 1163–1170.' mla: Oliveto, Pietro, et al. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–70, doi:10.1145/2908812.2908909. short: P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, B. Trubenova, in:, Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–1170. conference: end_date: 2016-07-24 location: Denver, CO, USA name: 'GECCO: Genetic and evolutionary computation conference' start_date: 2016-07-20 date_created: 2018-12-11T11:51:31Z date_published: 2016-07-20T00:00:00Z date_updated: 2021-01-12T06:50:03Z day: '20' ddc: - '576' department: - _id: NiBa - _id: CaGu doi: 10.1145/2908812.2908909 ec_funded: 1 file: - access_level: open_access checksum: a1896e39e4113f2711e46b435d5f3e69 content_type: application/pdf creator: system date_created: 2018-12-12T10:16:27Z date_updated: 2020-07-14T12:44:45Z file_id: '5214' file_name: IST-2016-650-v1+1_p1163-oliveto.pdf file_size: 979026 relation: main_file file_date_updated: 2020-07-14T12:44:45Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1163 - 1170 project: - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation publication: 'Proceedings of the Genetic and Evolutionary Computation Conference 2016 ' publication_status: published publisher: ACM publist_id: '5900' pubrep_id: '650' quality_controlled: '1' scopus_import: 1 status: public title: When non-elitism outperforms elitism for crossing fitness valleys 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 year: '2016' ... --- _id: '1359' abstract: - lang: eng text: "The role of gene interactions in the evolutionary process has long\r\nbeen controversial. Although some argue that they are not of\r\nimportance, because most variation is additive, others claim that\r\ntheir effect in the long term can be substantial. Here, we focus on\r\nthe long-term effects of genetic interactions under directional\r\nselection assuming no mutation or dominance, and that epistasis is\r\nsymmetrical overall. We ask by how much the mean of a complex\r\ntrait can be increased by selection and analyze two extreme\r\nregimes, in which either drift or selection dominate the dynamics\r\nof allele frequencies. In both scenarios, epistatic interactions affect\r\nthe long-term response to selection by modulating the additive\r\ngenetic variance. When drift dominates, we extend Robertson\r\n’\r\ns\r\n[Robertson A (1960)\r\nProc R Soc Lond B Biol Sci\r\n153(951):234\r\n−\r\n249]\r\nargument to show that, for any form of epistasis, the total response\r\nof a haploid population is proportional to the initial total genotypic\r\nvariance. In contrast, the total response of a diploid population is\r\nincreased by epistasis, for a given initial genotypic variance. When\r\nselection dominates, we show that the total selection response can\r\nonly be increased by epistasis when s\r\nome initially deleterious alleles\r\nbecome favored as the genetic background changes. We find a sim-\r\nple approximation for this effect and show that, in this regime, it is\r\nthe structure of the genotype - phenotype map that matters and not\r\nthe variance components of the population." article_processing_charge: No article_type: original author: - 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 citation: ama: Paixao T, Barton NH. The effect of gene interactions on the long-term response to selection. PNAS. 2016;113(16):4422-4427. doi:10.1073/pnas.1518830113 apa: Paixao, T., & Barton, N. H. (2016). The effect of gene interactions on the long-term response to selection. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1518830113 chicago: Paixao, Tiago, and Nicholas H Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS. National Academy of Sciences, 2016. https://doi.org/10.1073/pnas.1518830113. ieee: T. Paixao and N. H. Barton, “The effect of gene interactions on the long-term response to selection,” PNAS, vol. 113, no. 16. National Academy of Sciences, pp. 4422–4427, 2016. ista: Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term response to selection. PNAS. 113(16), 4422–4427. mla: Paixao, Tiago, and Nicholas H. Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS, vol. 113, no. 16, National Academy of Sciences, 2016, pp. 4422–27, doi:10.1073/pnas.1518830113. short: T. Paixao, N.H. Barton, PNAS 113 (2016) 4422–4427. date_created: 2018-12-11T11:51:34Z date_published: 2016-04-19T00:00:00Z date_updated: 2021-01-12T06:50:08Z day: '19' department: - _id: NiBa - _id: CaGu doi: 10.1073/pnas.1518830113 ec_funded: 1 external_id: pmid: - '27044080' intvolume: ' 113' issue: '16' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/ month: '04' oa: 1 oa_version: Published Version page: 4422 - 4427 pmid: 1 project: - _id: 25B07788-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '250152' name: Limits to selection in biology and in evolutionary computation - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation publication: PNAS publication_status: published publisher: National Academy of Sciences publist_id: '5886' quality_controlled: '1' scopus_import: 1 status: public title: The effect of gene interactions on the long-term response to selection type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 113 year: '2016' ... --- _id: '1427' abstract: - lang: eng text: Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner. author: - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler - first_name: Anaisa full_name: Moreno, Anaisa last_name: Moreno - 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: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: ama: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 2016;33(3):761-769. doi:10.1093/molbev/msv269 apa: Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269 chicago: Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269. ieee: M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic interactions in the arabinose cis-regulatory element,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016. ista: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3), 761–769. mla: Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269. short: M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769. date_created: 2018-12-11T11:51:57Z date_published: 2016-03-01T00:00:00Z date_updated: 2021-01-12T06:50:39Z day: '01' ddc: - '570' - '576' department: - _id: CaGu - _id: JoBo doi: 10.1093/molbev/msv269 ec_funded: 1 file: - access_level: open_access checksum: 1f456ce1d2aa2f67176a1709f9702ecf content_type: application/pdf creator: system date_created: 2018-12-12T10:09:27Z date_updated: 2020-07-14T12:44:53Z file_id: '4751' file_name: IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf file_size: 648115 relation: main_file file_date_updated: 2020-07-14T12:44:53Z has_accepted_license: '1' intvolume: ' 33' issue: '3' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 761 - 769 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Molecular Biology and Evolution publication_status: published publisher: Oxford University Press publist_id: '5772' pubrep_id: '588' quality_controlled: '1' scopus_import: 1 status: public title: Epistatic interactions in the arabinose 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 33 year: '2016' ... --- _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: '1250' abstract: - lang: eng text: In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported. acknowledgement: This manuscript is dedicated to the memory of Alex Böhm, who was a great friend and a passionate biologist. Alex passed away after the initial submission of this manuscript. We thank Vesna Olivera and Ursula Sauder from the Zentrum für Mikroskopie Uni Basel for excellent service, and Olin Silander, Nikki Freed, and Nela Nikolic for helpful discussions. This work was supported by the Swiss National Science Foundation grants to M. Ackermann and Urs Jenal (supporting AB). article_number: e1005974 author: - first_name: Alex full_name: Boehm, Alex last_name: Boehm - first_name: Markus full_name: Arnoldini, Markus last_name: Arnoldini - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Thomas full_name: Röösli, Thomas last_name: Röösli - first_name: Colette full_name: Bigosch, Colette last_name: Bigosch - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 2016;12(4). doi:10.1371/journal.pgen.1005974 apa: Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974 chicago: Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics. Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974. ieee: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Genetic manipulation of glycogen allocation affects replicative lifespan in E coli,” PLoS Genetics, vol. 12, no. 4. Public Library of Science, 2016. ista: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 12(4), e1005974. mla: Boehm, Alex, et al. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics, vol. 12, no. 4, e1005974, Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974. short: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, PLoS Genetics 12 (2016). date_created: 2018-12-11T11:50:56Z date_published: 2016-04-19T00:00:00Z date_updated: 2023-02-23T14:11:39Z day: '19' ddc: - '576' - '579' department: - _id: CaGu doi: 10.1371/journal.pgen.1005974 file: - access_level: open_access checksum: 53d22b2b39e5adc243d34f18b2615a85 content_type: application/pdf creator: system date_created: 2018-12-12T10:14:17Z date_updated: 2020-07-14T12:44:41Z file_id: '5067' file_name: IST-2016-705-v1+1_journal.pgen.1005974.PDF file_size: 6273249 relation: main_file file_date_updated: 2020-07-14T12:44:41Z has_accepted_license: '1' intvolume: ' 12' issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Published Version publication: PLoS Genetics publication_status: published publisher: Public Library of Science publist_id: '6077' pubrep_id: '705' quality_controlled: '1' related_material: record: - id: '9873' relation: research_data status: public scopus_import: 1 status: public title: Genetic manipulation of glycogen allocation affects replicative lifespan in E coli 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 12 year: '2016' ... --- _id: '9873' article_processing_charge: No author: - first_name: Alex full_name: Boehm, Alex last_name: Boehm - first_name: Markus full_name: Arnoldini, Markus last_name: Arnoldini - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Thomas full_name: Röösli, Thomas last_name: Röösli - first_name: Colette full_name: Bigosch, Colette last_name: Bigosch - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Quantification of the growth rate reduction as a consequence of age-specific mortality. 2016. doi:10.1371/journal.pgen.1005974.s015 apa: Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Quantification of the growth rate reduction as a consequence of age-specific mortality. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974.s015 chicago: Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality.” Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974.s015. ieee: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Quantification of the growth rate reduction as a consequence of age-specific mortality.” Public Library of Science, 2016. ista: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Quantification of the growth rate reduction as a consequence of age-specific mortality, Public Library of Science, 10.1371/journal.pgen.1005974.s015. mla: Boehm, Alex, et al. Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality. Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.s015. short: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, (2016). date_created: 2021-08-10T09:42:34Z date_updated: 2023-02-21T16:50:13Z day: '19' department: - _id: CaGu doi: 10.1371/journal.pgen.1005974.s015 month: '04' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '1250' relation: used_in_publication status: public status: public title: Quantification of the growth rate reduction as a consequence of age-specific mortality type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2016' ... --- _id: '5749' abstract: - lang: eng text: Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance. acknowledgement: The authors thank three anonymous reviewers and the editor for helpful comments on the manuscript, as well as Dominique Schneider for feedback on an earlier draft, Jenna Gallie for lytic λ and Julien Capelle for T5 and T6. This work was supported by the Swiss National Science Foundation (PZ00P3_148255 to A.H.) and an EU Marie Curie PEOPLE Postdoctoral Fellowship for Career Development (FP7-PEOPLE-2012-IEF-331824 to S.W.). article_processing_charge: No author: - first_name: Sébastien full_name: Wielgoss, Sébastien last_name: Wielgoss - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Anna M. full_name: Bischofberger, Anna M. last_name: Bischofberger - first_name: Alex R. full_name: Hall, Alex R. last_name: Hall citation: ama: Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. 2016;33(3):770-782. doi:10.1093/molbev/msv270 apa: Wielgoss, S., Bergmiller, T., Bischofberger, A. M., & Hall, A. R. (2016). Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv270 chicago: Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex R. Hall. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv270. ieee: S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 770–782, 2016. ista: Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2016. Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. 33(3), 770–782. mla: Wielgoss, Sébastien, et al. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 770–82, doi:10.1093/molbev/msv270. short: S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, Molecular Biology and Evolution 33 (2016) 770–782. date_created: 2018-12-18T13:18:10Z date_published: 2016-03-01T00:00:00Z date_updated: 2023-09-05T13:46:05Z day: '01' ddc: - '576' department: - _id: CaGu doi: 10.1093/molbev/msv270 external_id: pmid: - '26609077' file: - access_level: open_access checksum: 47d9010690b6c5c17f2ac830cc63ac5c content_type: application/pdf creator: dernst date_created: 2018-12-18T13:21:45Z date_updated: 2020-07-14T12:47:10Z file_id: '5750' file_name: 2016_MolBiolEvol_Wielgoss.pdf file_size: 634037 relation: main_file file_date_updated: 2020-07-14T12:47:10Z has_accepted_license: '1' intvolume: ' 33' issue: '3' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 770-782 pmid: 1 publication: Molecular Biology and Evolution publication_identifier: eissn: - 1537-1719 issn: - 0737-4038 publication_status: published publisher: Oxford University Press pubrep_id: '587' quality_controlled: '1' related_material: record: - id: '9719' relation: research_data status: public scopus_import: '1' status: public title: Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 33 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: '1243' abstract: - lang: eng text: Restriction-modification (RM) systems represent a minimal and ubiquitous biological system of self/non-self discrimination in prokaryotes [1], which protects hosts from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase (M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by methylating short specific DNA sequences called restriction sites, whereas R recognizes unmethylated restriction sites as non-self and introduces a double-stranded DNA break [3]. Restriction sites are significantly underrepresented in prokaryotic genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore, RM systems can promote DNA recombination [9] and contribute to genetic variation in microbial populations, thus facilitating adaptive evolution [10]. However, cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has not been directly detected, and its cause, frequency, and outcome are unknown. We quantify self-restriction caused by two RM systems of Escherichia coli and find that, in agreement with levels of restriction site avoidance, EcoRI, but not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic process, which temporarily induces the SOS response, and is followed by DNA repair, maintaining cell viability. We find that RM systems with higher restriction efficiency against bacteriophage infections exhibit a higher rate of self-restriction, and that this rate can be further increased by stochastic imbalance between R and M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic genomes. acknowledgement: This work was funded by an HFSP Young Investigators’ grant. M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria. R.O. and Y.W. were supported by the Platform for Dynamic Approaches to Living System from MEXT, Japan. We wish to thank I. Kobayashi for providing us with the EcoRI and EcoRV plasmids, and A. Campbell for providing us with the λ vir phage. We thank D. Siekhaus and C. Uhler and members of the C.C.G. and J.P. Bollback laboratories for in-depth discussions. We thank B. Stern for comments on an earlier version of the manuscript. We especially thank B.R. Levin for advice and comments, and the anonymous reviewers for significantly improving the manuscript. author: - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 - first_name: Long full_name: Qian, Long last_name: Qian - first_name: Reiko full_name: Okura, Reiko last_name: Okura - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Yuichi full_name: Wakamoto, Yuichi last_name: Wakamoto - first_name: Edo full_name: Kussell, Edo last_name: Kussell - 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, Qian L, Okura R, et al. Bacterial autoimmunity due to a restriction-modification system. Current Biology. 2016;26(3):404-409. doi:10.1016/j.cub.2015.12.041 apa: Pleska, M., Qian, L., Okura, R., Bergmiller, T., Wakamoto, Y., Kussell, E., & Guet, C. C. (2016). Bacterial autoimmunity due to a restriction-modification system. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2015.12.041 chicago: Pleska, Maros, Long Qian, Reiko Okura, Tobias Bergmiller, Yuichi Wakamoto, Edo Kussell, and Calin C Guet. “Bacterial Autoimmunity Due to a Restriction-Modification System.” Current Biology. Cell Press, 2016. https://doi.org/10.1016/j.cub.2015.12.041. ieee: M. Pleska et al., “Bacterial autoimmunity due to a restriction-modification system,” Current Biology, vol. 26, no. 3. Cell Press, pp. 404–409, 2016. ista: Pleska M, Qian L, Okura R, Bergmiller T, Wakamoto Y, Kussell E, Guet CC. 2016. Bacterial autoimmunity due to a restriction-modification system. Current Biology. 26(3), 404–409. mla: Pleska, Maros, et al. “Bacterial Autoimmunity Due to a Restriction-Modification System.” Current Biology, vol. 26, no. 3, Cell Press, 2016, pp. 404–09, doi:10.1016/j.cub.2015.12.041. short: M. Pleska, L. Qian, R. Okura, T. Bergmiller, Y. Wakamoto, E. Kussell, C.C. Guet, Current Biology 26 (2016) 404–409. date_created: 2018-12-11T11:50:54Z date_published: 2016-02-08T00:00:00Z date_updated: 2023-09-07T11:59:32Z day: '08' department: - _id: CaGu doi: 10.1016/j.cub.2015.12.041 intvolume: ' 26' issue: '3' language: - iso: eng month: '02' oa_version: None page: 404 - 409 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: Current Biology publication_status: published publisher: Cell Press publist_id: '6087' quality_controlled: '1' related_material: record: - id: '202' relation: dissertation_contains status: public scopus_import: 1 status: public title: Bacterial autoimmunity due to a restriction-modification system type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 26 year: '2016' ... --- _id: '1358' abstract: - lang: eng text: 'Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements.' article_number: '12307' author: - first_name: Tamar full_name: Friedlander, Tamar id: 36A5845C-F248-11E8-B48F-1D18A9856A87 last_name: Friedlander - first_name: Roshan full_name: Prizak, Roshan id: 4456104E-F248-11E8-B48F-1D18A9856A87 last_name: Prizak - 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: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik orcid: 0000-0002-6699-1455 citation: ama: Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 2016;7. doi:10.1038/ncomms12307 apa: Friedlander, T., Prizak, R., Guet, C. C., Barton, N. H., & Tkačik, G. (2016). Intrinsic limits to gene regulation by global crosstalk. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms12307 chicago: Friedlander, Tamar, Roshan Prizak, Calin C Guet, Nicholas H Barton, and Gašper Tkačik. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms12307. ieee: T. Friedlander, R. Prizak, C. C. Guet, N. H. Barton, and G. Tkačik, “Intrinsic limits to gene regulation by global crosstalk,” Nature Communications, vol. 7. Nature Publishing Group, 2016. ista: Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. 2016. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 7, 12307. mla: Friedlander, Tamar, et al. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” Nature Communications, vol. 7, 12307, Nature Publishing Group, 2016, doi:10.1038/ncomms12307. short: T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications 7 (2016). date_created: 2018-12-11T11:51:34Z date_published: 2016-08-04T00:00:00Z date_updated: 2023-09-07T12:53:49Z day: '04' ddc: - '576' department: - _id: GaTk - _id: NiBa - _id: CaGu doi: 10.1038/ncomms12307 ec_funded: 1 file: - access_level: open_access checksum: fe3f3a1526d180b29fe691ab11435b78 content_type: application/pdf creator: system date_created: 2018-12-12T10:12:01Z date_updated: 2020-07-14T12:44:46Z file_id: '4919' file_name: IST-2016-627-v1+1_ncomms12307.pdf file_size: 861805 relation: main_file - access_level: open_access checksum: 164864a1a675f3ad80e9917c27aba07f content_type: application/pdf creator: system date_created: 2018-12-12T10:12:02Z date_updated: 2020-07-14T12:44:46Z file_id: '4920' file_name: IST-2016-627-v1+2_ncomms12307-s1.pdf file_size: 1084703 relation: main_file file_date_updated: 2020-07-14T12:44:46Z has_accepted_license: '1' intvolume: ' 7' language: - iso: eng month: '08' oa: 1 oa_version: Published Version project: - _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 - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Nature Communications publication_status: published publisher: Nature Publishing Group publist_id: '5887' pubrep_id: '627' quality_controlled: '1' related_material: record: - id: '6071' relation: dissertation_contains status: public scopus_import: 1 status: public title: Intrinsic limits to gene regulation by global crosstalk 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 7 year: '2016' ... --- _id: '1430' 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 their runtime 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 occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (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. author: - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Dirk full_name: Sudholt, Dirk last_name: Sudholt - first_name: Jorge full_name: Heredia, Jorge last_name: Heredia - 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, Sudholt D, Heredia J, Trubenova B. First steps towards a runtime comparison of natural and artificial evolution. In: Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation. ACM; 2015:1455-1462. doi:10.1145/2739480.2754758' apa: 'Paixao, T., Sudholt, D., Heredia, J., & Trubenova, B. (2015). First steps towards a runtime comparison of natural and artificial evolution. In Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation (pp. 1455–1462). Madrid, Spain: ACM. https://doi.org/10.1145/2739480.2754758' chicago: Paixao, Tiago, Dirk Sudholt, Jorge Heredia, and Barbora Trubenova. “First Steps towards a Runtime Comparison of Natural and Artificial Evolution.” In Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, 1455–62. ACM, 2015. https://doi.org/10.1145/2739480.2754758. ieee: T. Paixao, D. Sudholt, J. Heredia, and B. Trubenova, “First steps towards a runtime comparison of natural and artificial evolution,” in Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, Madrid, Spain, 2015, pp. 1455–1462. ista: 'Paixao T, Sudholt D, Heredia J, Trubenova B. 2015. First steps towards a runtime comparison of natural and artificial evolution. Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation. GECCO: Genetic and evolutionary computation conference, 1455–1462.' mla: Paixao, Tiago, et al. “First Steps towards a Runtime Comparison of Natural and Artificial Evolution.” Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, ACM, 2015, pp. 1455–62, doi:10.1145/2739480.2754758. short: T. Paixao, D. Sudholt, J. Heredia, B. Trubenova, in:, Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, ACM, 2015, pp. 1455–1462. conference: end_date: 2015-07-15 location: Madrid, Spain name: 'GECCO: Genetic and evolutionary computation conference' start_date: 2015-07-11 date_created: 2018-12-11T11:51:58Z date_published: 2015-07-11T00:00:00Z date_updated: 2021-01-12T06:50:41Z day: '11' department: - _id: NiBa - _id: CaGu doi: 10.1145/2739480.2754758 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: http://arxiv.org/abs/1504.06260 month: '07' oa: 1 oa_version: Preprint page: 1455 - 1462 project: - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation publication: Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation publication_status: published publisher: ACM publist_id: '5768' quality_controlled: '1' scopus_import: 1 status: public title: First steps towards a runtime comparison of natural and artificial evolution type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2015' ... --- _id: '1542' abstract: - lang: eng text: 'The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. ' author: - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Golnaz full_name: Badkobeh, Golnaz last_name: Badkobeh - 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: Doğan full_name: Çörüş, Doğan last_name: Çörüş - first_name: Duccuong full_name: Dang, Duccuong last_name: Dang - first_name: Tobias full_name: Friedrich, Tobias last_name: Friedrich - first_name: Per full_name: Lehre, Per last_name: Lehre - first_name: Dirk full_name: Sudholt, Dirk last_name: Sudholt - first_name: Andrew full_name: Sutton, Andrew last_name: Sutton - 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, Badkobeh G, Barton NH, et al. Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. 2015;383:28-43. doi:10.1016/j.jtbi.2015.07.011 apa: Paixao, T., Badkobeh, G., Barton, N. H., Çörüş, D., Dang, D., Friedrich, T., … Trubenova, B. (2015). Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. Elsevier. https://doi.org/10.1016/j.jtbi.2015.07.011 chicago: Paixao, Tiago, Golnaz Badkobeh, Nicholas H Barton, Doğan Çörüş, Duccuong Dang, Tobias Friedrich, Per Lehre, Dirk Sudholt, Andrew Sutton, and Barbora Trubenova. “Toward a Unifying Framework for Evolutionary Processes.” Journal of Theoretical Biology. Elsevier, 2015. https://doi.org/10.1016/j.jtbi.2015.07.011. ieee: T. Paixao et al., “Toward a unifying framework for evolutionary processes,” Journal of Theoretical Biology, vol. 383. Elsevier, pp. 28–43, 2015. ista: Paixao T, Badkobeh G, Barton NH, Çörüş D, Dang D, Friedrich T, Lehre P, Sudholt D, Sutton A, Trubenova B. 2015. Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. 383, 28–43. mla: Paixao, Tiago, et al. “Toward a Unifying Framework for Evolutionary Processes.” Journal of Theoretical Biology, vol. 383, Elsevier, 2015, pp. 28–43, doi:10.1016/j.jtbi.2015.07.011. short: T. Paixao, G. Badkobeh, N.H. Barton, D. Çörüş, D. Dang, T. Friedrich, P. Lehre, D. Sudholt, A. Sutton, B. Trubenova, Journal of Theoretical Biology 383 (2015) 28–43. date_created: 2018-12-11T11:52:37Z date_published: 2015-10-21T00:00:00Z date_updated: 2021-01-12T06:51:29Z day: '21' ddc: - '570' department: - _id: NiBa - _id: CaGu doi: 10.1016/j.jtbi.2015.07.011 ec_funded: 1 file: - access_level: open_access checksum: 33b60ecfea60764756a9ee9df5eb65ca content_type: application/pdf creator: system date_created: 2018-12-12T10:16:53Z date_updated: 2020-07-14T12:45:01Z file_id: '5244' file_name: IST-2016-483-v1+1_1-s2.0-S0022519315003409-main.pdf file_size: 595307 relation: main_file file_date_updated: 2020-07-14T12:45:01Z has_accepted_license: '1' intvolume: ' 383' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: 28 - 43 project: - _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 publication: ' Journal of Theoretical Biology' publication_status: published publisher: Elsevier publist_id: '5629' pubrep_id: '483' quality_controlled: '1' scopus_import: 1 status: public title: Toward a unifying framework for evolutionary processes tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 383 year: '2015' ... --- _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: '9712' article_processing_charge: No author: - first_name: Murat full_name: Tugrul, Murat id: 37C323C6-F248-11E8-B48F-1D18A9856A87 last_name: Tugrul orcid: 0000-0002-8523-0758 - 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: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Tugrul M, Paixao T, Barton NH, Tkačik G. Other fitness models for comparison & for interacting TFBSs. 2015. doi:10.1371/journal.pgen.1005639.s001 apa: Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Other fitness models for comparison & for interacting TFBSs. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005639.s001 chicago: Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Other Fitness Models for Comparison & for Interacting TFBSs.” Public Library of Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.s001. ieee: M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for comparison & for interacting TFBSs.” Public Library of Science, 2015. ista: Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Other fitness models for comparison & for interacting TFBSs, Public Library of Science, 10.1371/journal.pgen.1005639.s001. mla: Tugrul, Murat, et al. Other Fitness Models for Comparison & for Interacting TFBSs. Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.s001. short: M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, (2015). date_created: 2021-07-23T12:00:37Z date_published: 2015-11-06T00:00:00Z date_updated: 2023-02-23T10:09:08Z day: '06' department: - _id: NiBa - _id: CaGu - _id: GaTk doi: 10.1371/journal.pgen.1005639.s001 month: '11' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '1666' relation: used_in_publication status: public status: public title: Other fitness models for comparison & for interacting TFBSs type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2015' ... --- _id: '9719' abstract: - lang: eng text: Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance. article_processing_charge: No author: - first_name: Sébastien full_name: Wielgoss, Sébastien last_name: Wielgoss - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Anna M. full_name: Bischofberger, Anna M. last_name: Bischofberger - first_name: Alex R. full_name: Hall, Alex R. last_name: Hall citation: ama: 'Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria. 2015. doi:10.5061/dryad.cj910' apa: 'Wielgoss, S., Bergmiller, T., Bischofberger, A. M., & Hall, A. R. (2015). Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria. Dryad. https://doi.org/10.5061/dryad.cj910' chicago: 'Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex R. Hall. “Data from: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Non-Mutator Bacteria.” Dryad, 2015. https://doi.org/10.5061/dryad.cj910.' ieee: 'S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria.” Dryad, 2015.' ista: 'Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2015. Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria, Dryad, 10.5061/dryad.cj910.' mla: 'Wielgoss, Sébastien, et al. Data from: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Non-Mutator Bacteria. Dryad, 2015, doi:10.5061/dryad.cj910.' short: S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, (2015). date_created: 2021-07-26T08:44:04Z date_published: 2015-12-21T00:00:00Z date_updated: 2023-09-05T13:46:04Z day: '21' department: - _id: CaGu doi: 10.5061/dryad.cj910 main_file_link: - open_access: '1' url: https://doi.org/10.5061/dryad.cj910 month: '12' oa: 1 oa_version: Published Version publisher: Dryad related_material: record: - id: '5749' relation: used_in_publication status: public status: public title: 'Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria' type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2015' ...