[{"month":"02","oa_version":"Published Version","acknowledged_ssus":[{"_id":"ScienComp"}],"project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"},{"name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?","grant_number":"RGP0034/2018","_id":"2665AAFE-B435-11E9-9278-68D0E5697425"},{"_id":"bd6958e0-d553-11ed-ba76-86eba6a76c00","grant_number":"101055327","name":"Understanding the evolution of continuous genomes"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"keyword":["Theoretical biology","Optimality","Evolution","Information"],"supervisor":[{"full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","last_name":"Barton","first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"publication_identifier":{"issn":["2663 - 337X"]},"date_published":"2024-02-23T00:00:00Z","type":"dissertation","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","related_material":{"record":[{"status":"public","id":"7553","relation":"part_of_dissertation"},{"status":"public","relation":"part_of_dissertation","id":"7606"},{"relation":"part_of_dissertation","id":"12081","status":"public"}]},"file":[{"date_created":"2024-02-23T13:50:53Z","checksum":"b2d3da47c98d481577a4baf68944fe41","file_size":7102089,"date_updated":"2024-02-23T13:50:53Z","content_type":"application/pdf","file_name":"hledik thesis pdfa 2b.pdf","success":1,"access_level":"open_access","relation":"main_file","file_id":"15021","creator":"mhledik"},{"checksum":"eda9b9430da2610fee7ce1c1419a479a","file_size":14014790,"date_created":"2024-02-23T13:50:54Z","content_type":"application/zip","file_name":"hledik thesis source.zip","date_updated":"2024-02-23T14:20:16Z","relation":"source_file","access_level":"closed","creator":"mhledik","file_id":"15022"}],"title":"Genetic information and biological optimization","alternative_title":["ISTA Thesis"],"publication_status":"published","date_created":"2024-02-23T14:02:04Z","article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"GaTk"}],"author":[{"id":"4171253A-F248-11E8-B48F-1D18A9856A87","first_name":"Michal","last_name":"Hledik","full_name":"Hledik, Michal"}],"_id":"15020","publisher":"Institute of Science and Technology Austria","file_date_updated":"2024-02-23T14:20:16Z","page":"158","ec_funded":1,"abstract":[{"text":"This thesis consists of four distinct pieces of work within theoretical biology, with two themes in common: the concept of optimization in biological systems, and the use of information-theoretic tools to quantify biological stochasticity and statistical uncertainty.\r\nChapter 2 develops a statistical framework for studying biological systems which we believe to be optimized for a particular utility function, such as retinal neurons conveying information about visual stimuli. We formalize such beliefs as maximum-entropy Bayesian priors, constrained by the expected utility. We explore how such priors aid inference of system parameters with limited data and enable optimality hypothesis testing: is the utility higher than by chance?\r\nChapter 3 examines the ultimate biological optimization process: evolution by natural selection. As some individuals survive and reproduce more successfully than others, populations evolve towards fitter genotypes and phenotypes. We formalize this as accumulation of genetic information, and use population genetics theory to study how much such information can be accumulated per generation and maintained in the face of random mutation and genetic drift. We identify the population size and fitness variance as the key quantities that control information accumulation and maintenance.\r\nChapter 4 reuses the concept of genetic information from Chapter 3, but from a different perspective: we ask how much genetic information organisms actually need, in particular in the context of gene regulation. For example, how much information is needed to bind transcription factors at correct locations within the genome? Population genetics provides us with a refined answer: with an increasing population size, populations achieve higher fitness by maintaining more genetic information. Moreover, regulatory parameters experience selection pressure to optimize the fitness-information trade-off, i.e. minimize the information needed for a given fitness. This provides an evolutionary derivation of the optimization priors introduced in Chapter 2.\r\nChapter 5 proves an upper bound on mutual information between a signal and a communication channel output (such as neural activity). Mutual information is an important utility measure for biological systems, but its practical use can be difficult due to the large dimensionality of many biological channels. Sometimes, a lower bound on mutual information is computed by replacing the high-dimensional channel outputs with decodes (signal estimates). Our result provides a corresponding upper bound, provided that the decodes are the maximum posterior estimates of the signal.","lang":"eng"}],"doi":"10.15479/at:ista:15020","day":"23","date_updated":"2025-06-30T13:21:09Z","citation":{"ieee":"M. Hledik, “Genetic information and biological optimization,” Institute of Science and Technology Austria, 2024.","chicago":"Hledik, Michal. “Genetic Information and Biological Optimization.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15020\">https://doi.org/10.15479/at:ista:15020</a>.","ama":"Hledik M. Genetic information and biological optimization. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15020\">10.15479/at:ista:15020</a>","apa":"Hledik, M. (2024). <i>Genetic information and biological optimization</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15020\">https://doi.org/10.15479/at:ista:15020</a>","ista":"Hledik M. 2024. Genetic information and biological optimization. Institute of Science and Technology Austria.","mla":"Hledik, Michal. <i>Genetic Information and Biological Optimization</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15020\">10.15479/at:ista:15020</a>.","short":"M. Hledik, Genetic Information and Biological Optimization, Institute of Science and Technology Austria, 2024."},"year":"2024","ddc":["576","519"]},{"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","main_file_link":[{"url":"https://doi.org/10.48550/arXiv.2101.12426","open_access":"1"}],"oa":1,"publication_identifier":{"issn":["0018-9448"],"eissn":["1557-9654"]},"type":"journal_article","date_published":"2023-07-01T00:00:00Z","keyword":["Computer Science Applications","Information Systems"],"language":[{"iso":"eng"}],"month":"07","oa_version":"Preprint","publication":"IEEE Transactions on Information Theory","volume":69,"acknowledgement":"The author would like to thank Amitalok J. Budkuley and Sidharth Jaggi for many helpful discussions at the early stage of this work. He would also like to thank Nir Ailon, Qi Cao, and Chandra Nair for discussions on a related problem regarding zero-error binary adder MACs.\r\nThe work of Yihan Zhang was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant 682203-ERC-[Inf-Speed-Tradeoff]","abstract":[{"lang":"eng","text":"We consider zero-error communication over a two-transmitter deterministic adversarial multiple access channel (MAC) governed by an adversary who has access to the transmissions of both senders (hence called omniscient ) and aims to maliciously corrupt the communication. None of the encoders, jammer and decoder is allowed to randomize using private or public randomness. This enforces a combinatorial nature of the problem. Our model covers a large family of channels studied in the literature, including all deterministic discrete memoryless noisy or noiseless MACs. In this work, given an arbitrary two-transmitter deterministic omniscient adversarial MAC, we characterize when the capacity region: 1) has nonempty interior (in particular, is two-dimensional); 2) consists of two line segments (in particular, has empty interior); 3) consists of one line segment (in particular, is one-dimensional); 4) or only contains (0,0) (in particular, is zero-dimensional). This extends a recent result by Wang et al. (201 9) from the point-to-point setting to the multiple access setting. Indeed, our converse arguments build upon their generalized Plotkin bound and involve delicate case analysis. One of the technical challenges is to take care of both “joint confusability” and “marginal confusability”. In particular, the treatment of marginal confusability does not follow from the point-to-point results by Wang et al. Our achievability results follow from random coding with expurgation."}],"day":"01","doi":"10.1109/tit.2023.3257239","arxiv":1,"external_id":{"arxiv":["2101.12426"]},"citation":{"ista":"Zhang Y. 2023. Zero-error communication over adversarial MACs. IEEE Transactions on Information Theory. 69(7), 4093–4127.","short":"Y. Zhang, IEEE Transactions on Information Theory 69 (2023) 4093–4127.","mla":"Zhang, Yihan. “Zero-Error Communication over Adversarial MACs.” <i>IEEE Transactions on Information Theory</i>, vol. 69, no. 7, Institute of Electrical and Electronics Engineers, 2023, pp. 4093–127, doi:<a href=\"https://doi.org/10.1109/tit.2023.3257239\">10.1109/tit.2023.3257239</a>.","chicago":"Zhang, Yihan. “Zero-Error Communication over Adversarial MACs.” <i>IEEE Transactions on Information Theory</i>. Institute of Electrical and Electronics Engineers, 2023. <a href=\"https://doi.org/10.1109/tit.2023.3257239\">https://doi.org/10.1109/tit.2023.3257239</a>.","ieee":"Y. Zhang, “Zero-error communication over adversarial MACs,” <i>IEEE Transactions on Information Theory</i>, vol. 69, no. 7. Institute of Electrical and Electronics Engineers, pp. 4093–4127, 2023.","ama":"Zhang Y. Zero-error communication over adversarial MACs. <i>IEEE Transactions on Information Theory</i>. 2023;69(7):4093-4127. doi:<a href=\"https://doi.org/10.1109/tit.2023.3257239\">10.1109/tit.2023.3257239</a>","apa":"Zhang, Y. (2023). Zero-error communication over adversarial MACs. <i>IEEE Transactions on Information Theory</i>. Institute of Electrical and Electronics Engineers. <a href=\"https://doi.org/10.1109/tit.2023.3257239\">https://doi.org/10.1109/tit.2023.3257239</a>"},"year":"2023","date_updated":"2024-01-09T08:45:24Z","article_type":"original","publisher":"Institute of Electrical and Electronics Engineers","quality_controlled":"1","page":"4093-4127","intvolume":"        69","title":"Zero-error communication over adversarial MACs","department":[{"_id":"MaMo"}],"date_created":"2024-01-08T13:04:54Z","article_processing_charge":"No","publication_status":"published","issue":"7","author":[{"id":"2ce5da42-b2ea-11eb-bba5-9f264e9d002c","last_name":"Zhang","first_name":"Yihan","full_name":"Zhang, Yihan","orcid":"0000-0002-6465-6258"}],"scopus_import":"1","_id":"14751"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2022-10-01T00:00:00Z","publication_identifier":{"eissn":["1432-0525"],"issn":["0001-5903"]},"oa":1,"file":[{"creator":"cchlebak","file_id":"10603","success":1,"relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2021_ActaInfor_Křetínský.pdf","date_updated":"2022-01-07T07:50:31Z","checksum":"bf1c195b6aaf59e8530cf9e3a9d731f7","file_size":1066082,"date_created":"2022-01-07T07:50:31Z"}],"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","has_accepted_license":"1","publication":"Acta Informatica","project":[{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"}],"oa_version":"Published Version","month":"10","keyword":["computer networks and communications","information systems","software"],"language":[{"iso":"eng"}],"citation":{"mla":"Kretinsky, Jan, et al. “Index Appearance Record with Preorders.” <i>Acta Informatica</i>, vol. 59, Springer Nature, 2022, pp. 585–618, doi:<a href=\"https://doi.org/10.1007/s00236-021-00412-y\">10.1007/s00236-021-00412-y</a>.","short":"J. Kretinsky, T. Meggendorfer, C. Waldmann, M. Weininger, Acta Informatica 59 (2022) 585–618.","ista":"Kretinsky J, Meggendorfer T, Waldmann C, Weininger M. 2022. Index appearance record with preorders. Acta Informatica. 59, 585–618.","ama":"Kretinsky J, Meggendorfer T, Waldmann C, Weininger M. Index appearance record with preorders. <i>Acta Informatica</i>. 2022;59:585-618. doi:<a href=\"https://doi.org/10.1007/s00236-021-00412-y\">10.1007/s00236-021-00412-y</a>","apa":"Kretinsky, J., Meggendorfer, T., Waldmann, C., &#38; Weininger, M. (2022). Index appearance record with preorders. <i>Acta Informatica</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s00236-021-00412-y\">https://doi.org/10.1007/s00236-021-00412-y</a>","ieee":"J. Kretinsky, T. Meggendorfer, C. Waldmann, and M. Weininger, “Index appearance record with preorders,” <i>Acta Informatica</i>, vol. 59. Springer Nature, pp. 585–618, 2022.","chicago":"Kretinsky, Jan, Tobias Meggendorfer, Clara Waldmann, and Maximilian Weininger. “Index Appearance Record with Preorders.” <i>Acta Informatica</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1007/s00236-021-00412-y\">https://doi.org/10.1007/s00236-021-00412-y</a>."},"year":"2022","date_updated":"2023-08-02T13:49:28Z","external_id":{"isi":["000735765500001"]},"isi":1,"day":"01","doi":"10.1007/s00236-021-00412-y","abstract":[{"text":"Transforming ω-automata into parity automata is traditionally done using appearance records. We present an efficient variant of this idea, tailored to Rabin automata, and several optimizations applicable to all appearance records. We compare the methods experimentally and show that our method produces significantly smaller automata than previous approaches.","lang":"eng"}],"acknowledgement":"This work is partially funded by the German Research Foundation (DFG) projects Verified Model Checkers (No. 317422601) and Statistical Unbounded Verification (No. 383882557), and the Alexander von Humboldt Foundation with funds from the German Federal Ministry of Education and Research. It is an extended version of [21], including all proofs together with further explanations and examples. Moreover, we provide a new, more efficient construction based on (total) preorders, unifying previous optimizations. Experiments are performed with a new, performant implementation, comparing our approach to the current state of the art.","volume":59,"ddc":["000"],"scopus_import":"1","license":"https://creativecommons.org/licenses/by/4.0/","_id":"10602","author":[{"last_name":"Kretinsky","first_name":"Jan","full_name":"Kretinsky, Jan","orcid":"0000-0002-8122-2881","id":"44CEF464-F248-11E8-B48F-1D18A9856A87"},{"id":"b21b0c15-30a2-11eb-80dc-f13ca25802e1","first_name":"Tobias","last_name":"Meggendorfer","orcid":"0000-0002-1712-2165","full_name":"Meggendorfer, Tobias"},{"first_name":"Clara","last_name":"Waldmann","full_name":"Waldmann, Clara"},{"last_name":"Weininger","first_name":"Maximilian","full_name":"Weininger, Maximilian"}],"date_created":"2022-01-06T12:37:27Z","article_processing_charge":"Yes (via OA deal)","department":[{"_id":"KrCh"}],"publication_status":"published","intvolume":"        59","title":"Index appearance record with preorders","quality_controlled":"1","page":"585-618","file_date_updated":"2022-01-07T07:50:31Z","publisher":"Springer Nature","article_type":"original"},{"file":[{"content_type":"application/pdf","file_name":"2022_JourPhysics_Boerner.pdf","date_updated":"2023-01-24T07:24:37Z","checksum":"35c5c5cb0eb17ea1b5184755daab9fc9","file_size":1006106,"date_created":"2023-01-24T07:24:37Z","creator":"dernst","file_id":"12350","access_level":"open_access","relation":"main_file","success":1}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","publication_identifier":{"issn":["2632-072X"]},"oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2022-10-25T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"keyword":["Artificial Intelligence","Computer Networks and Communications","Computer Science Applications","Information Systems"],"oa_version":"Published Version","month":"10","article_number":"04LT02","publication":"Journal of Physics: Complexity","has_accepted_license":"1","volume":3,"acknowledgement":"We acknowledge support from the Volkswagen Foundation under Grant No. 99720 and the German Federal Ministry for Education and Research (BMBF) under Grant No. 16ICR01. This research was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2068—390729961—Cluster of Excellence Physics of Life of TU Dresden.","ddc":["530"],"doi":"10.1088/2632-072x/ac99cd","day":"25","abstract":[{"lang":"eng","text":"Standard epidemic models exhibit one continuous, second order phase transition to macroscopic outbreaks. However, interventions to control outbreaks may fundamentally alter epidemic dynamics. Here we reveal how such interventions modify the type of phase transition. In particular, we uncover three distinct types of explosive phase transitions for epidemic dynamics with capacity-limited interventions. Depending on the capacity limit, interventions may (i) leave the standard second order phase transition unchanged but exponentially suppress the probability of large outbreaks, (ii) induce a first-order discontinuous transition to macroscopic outbreaks, or (iii) cause a secondary explosive yet continuous third-order transition. These insights highlight inherent limitations in predicting and containing epidemic outbreaks. More generally our study offers a cornerstone example of a third-order explosive phase transition in complex systems."}],"date_updated":"2023-02-13T09:15:13Z","year":"2022","citation":{"short":"G. Börner, M. Schröder, D. Scarselli, N.B. Budanur, B. Hof, M. Timme, Journal of Physics: Complexity 3 (2022).","mla":"Börner, Georg, et al. “Explosive Transitions in Epidemic Dynamics.” <i>Journal of Physics: Complexity</i>, vol. 3, no. 4, 04LT02, IOP Publishing, 2022, doi:<a href=\"https://doi.org/10.1088/2632-072x/ac99cd\">10.1088/2632-072x/ac99cd</a>.","ista":"Börner G, Schröder M, Scarselli D, Budanur NB, Hof B, Timme M. 2022. Explosive transitions in epidemic dynamics. Journal of Physics: Complexity. 3(4), 04LT02.","ama":"Börner G, Schröder M, Scarselli D, Budanur NB, Hof B, Timme M. Explosive transitions in epidemic dynamics. <i>Journal of Physics: Complexity</i>. 2022;3(4). doi:<a href=\"https://doi.org/10.1088/2632-072x/ac99cd\">10.1088/2632-072x/ac99cd</a>","apa":"Börner, G., Schröder, M., Scarselli, D., Budanur, N. B., Hof, B., &#38; Timme, M. (2022). Explosive transitions in epidemic dynamics. <i>Journal of Physics: Complexity</i>. IOP Publishing. <a href=\"https://doi.org/10.1088/2632-072x/ac99cd\">https://doi.org/10.1088/2632-072x/ac99cd</a>","ieee":"G. Börner, M. Schröder, D. Scarselli, N. B. Budanur, B. Hof, and M. Timme, “Explosive transitions in epidemic dynamics,” <i>Journal of Physics: Complexity</i>, vol. 3, no. 4. IOP Publishing, 2022.","chicago":"Börner, Georg, Malte Schröder, Davide Scarselli, Nazmi B Budanur, Björn Hof, and Marc Timme. “Explosive Transitions in Epidemic Dynamics.” <i>Journal of Physics: Complexity</i>. IOP Publishing, 2022. <a href=\"https://doi.org/10.1088/2632-072x/ac99cd\">https://doi.org/10.1088/2632-072x/ac99cd</a>."},"publisher":"IOP Publishing","article_type":"original","quality_controlled":"1","file_date_updated":"2023-01-24T07:24:37Z","publication_status":"published","article_processing_charge":"No","department":[{"_id":"BjHo"}],"date_created":"2023-01-12T12:03:43Z","title":"Explosive transitions in epidemic dynamics","intvolume":"         3","_id":"12134","scopus_import":"1","author":[{"full_name":"Börner, Georg","last_name":"Börner","first_name":"Georg"},{"full_name":"Schröder, Malte","last_name":"Schröder","first_name":"Malte"},{"id":"40315C30-F248-11E8-B48F-1D18A9856A87","full_name":"Scarselli, Davide","orcid":"0000-0001-5227-4271","last_name":"Scarselli","first_name":"Davide"},{"id":"3EA1010E-F248-11E8-B48F-1D18A9856A87","first_name":"Nazmi B","last_name":"Budanur","orcid":"0000-0003-0423-5010","full_name":"Budanur, Nazmi B"},{"id":"3A374330-F248-11E8-B48F-1D18A9856A87","full_name":"Hof, Björn","orcid":"0000-0003-2057-2754","last_name":"Hof","first_name":"Björn"},{"first_name":"Marc","last_name":"Timme","full_name":"Timme, Marc"}],"issue":"4"},{"file":[{"access_level":"open_access","success":1,"relation":"main_file","file_id":"12446","creator":"dernst","date_created":"2023-01-30T09:49:55Z","file_size":1098812,"checksum":"8b1d8f5ea20c8408acf466435fb6ae01","date_updated":"2023-01-30T09:49:55Z","file_name":"2022_MolecularSystemsBio_Angermayr.pdf","content_type":"application/pdf"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","publication_identifier":{"eissn":["1744-4292"]},"oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2022-09-01T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"keyword":["Applied Mathematics","Computational Theory and Mathematics","General Agricultural and Biological Sciences","General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","Information Systems"],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"M-Shop"}],"month":"09","article_number":"e10490","publication":"Molecular Systems Biology","has_accepted_license":"1","volume":18,"acknowledgement":"This work was in part supported by Human Frontier Science Program GrantRGP0042/2013, Marie Curie Career Integration Grant303507, AustrianScience Fund (FWF) Grant P27201-B22, and German Research Foundation(DFG) Collaborative Research Center (SFB)1310to TB. SAA was supportedby the European Union’s Horizon2020Research and Innovation Programunder the Marie Skłodowska-Curie Grant agreement No707352. We wouldlike to thank the Bollenbach group for regular fruitful discussions. We areparticularly thankful for the technical assistance of Booshini Fernando andfor discussions of the theoretical aspects with Gerrit Ansmann. We areindebted to Bor Kavˇciˇc for invaluable advice, help with setting up theluciferase-based growth monitoring system, and for sharing plasmids. Weacknowledge the IST Austria Miba Machine Shop for their support inbuilding a housing for the stacker of the plate reader, which enabled thehigh-throughput luciferase-based experiments. We are grateful to RosalindAllen, Bor Kavˇciˇc and Dor Russ for feedback on the manuscript. Open Accessfunding enabled and organized by Projekt DEAL.","ddc":["570"],"doi":"10.15252/msb.202110490","day":"01","abstract":[{"lang":"eng","text":"Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance."}],"date_updated":"2023-08-04T09:51:49Z","citation":{"ieee":"A. Angermayr, T. Y. Pang, G. Chevereau, K. Mitosch, M. J. Lercher, and M. T. Bollenbach, “Growth‐mediated negative feedback shapes quantitative antibiotic response,” <i>Molecular Systems Biology</i>, vol. 18, no. 9. Embo Press, 2022.","chicago":"Angermayr, Andreas, Tin Yau Pang, Guillaume Chevereau, Karin Mitosch, Martin J Lercher, and Mark Tobias Bollenbach. “Growth‐mediated Negative Feedback Shapes Quantitative Antibiotic Response.” <i>Molecular Systems Biology</i>. Embo Press, 2022. <a href=\"https://doi.org/10.15252/msb.202110490\">https://doi.org/10.15252/msb.202110490</a>.","apa":"Angermayr, A., Pang, T. Y., Chevereau, G., Mitosch, K., Lercher, M. J., &#38; Bollenbach, M. T. (2022). Growth‐mediated negative feedback shapes quantitative antibiotic response. <i>Molecular Systems Biology</i>. Embo Press. <a href=\"https://doi.org/10.15252/msb.202110490\">https://doi.org/10.15252/msb.202110490</a>","ama":"Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. Growth‐mediated negative feedback shapes quantitative antibiotic response. <i>Molecular Systems Biology</i>. 2022;18(9). doi:<a href=\"https://doi.org/10.15252/msb.202110490\">10.15252/msb.202110490</a>","ista":"Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. 2022. Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular Systems Biology. 18(9), e10490.","mla":"Angermayr, Andreas, et al. “Growth‐mediated Negative Feedback Shapes Quantitative Antibiotic Response.” <i>Molecular Systems Biology</i>, vol. 18, no. 9, e10490, Embo Press, 2022, doi:<a href=\"https://doi.org/10.15252/msb.202110490\">10.15252/msb.202110490</a>.","short":"A. Angermayr, T.Y. Pang, G. Chevereau, K. Mitosch, M.J. Lercher, M.T. Bollenbach, Molecular Systems Biology 18 (2022)."},"year":"2022","isi":1,"external_id":{"isi":["000856482800001"]},"publisher":"Embo Press","article_type":"original","quality_controlled":"1","file_date_updated":"2023-01-30T09:49:55Z","publication_status":"published","department":[{"_id":"ToBo"}],"article_processing_charge":"No","date_created":"2023-01-16T09:58:34Z","title":"Growth‐mediated negative feedback shapes quantitative antibiotic response","intvolume":"        18","_id":"12261","scopus_import":"1","author":[{"orcid":"0000-0001-8619-2223","full_name":"Angermayr, Andreas","first_name":"Andreas","last_name":"Angermayr","id":"4677C796-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Pang, Tin Yau","last_name":"Pang","first_name":"Tin Yau"},{"last_name":"Chevereau","first_name":"Guillaume","full_name":"Chevereau, Guillaume"},{"first_name":"Karin","last_name":"Mitosch","full_name":"Mitosch, Karin","id":"39B66846-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lercher, Martin J","first_name":"Martin J","last_name":"Lercher"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","last_name":"Bollenbach","first_name":"Mark Tobias","full_name":"Bollenbach, Mark Tobias","orcid":"0000-0003-4398-476X"}],"issue":"9"},{"language":[{"iso":"eng"}],"keyword":["Information Systems","Software"],"oa_version":"None","month":"08","publication":"International Journal on Software Tools for Technology Transfer","related_material":{"record":[{"status":"public","id":"299","relation":"earlier_version"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","publication_identifier":{"issn":["1433-2779"],"eissn":["1433-2787"]},"date_published":"2020-08-03T00:00:00Z","type":"journal_article","publisher":"Springer Nature","article_type":"original","page":"741-758","quality_controlled":"1","publication_status":"published","article_processing_charge":"No","date_created":"2022-03-18T10:10:53Z","department":[{"_id":"ToHe"}],"title":"AMT 2.0: Qualitative and quantitative trace analysis with extended signal temporal logic","intvolume":"        22","_id":"10861","scopus_import":"1","author":[{"id":"41BCEE5C-F248-11E8-B48F-1D18A9856A87","full_name":"Nickovic, Dejan","last_name":"Nickovic","first_name":"Dejan"},{"last_name":"Lebeltel","first_name":"Olivier","full_name":"Lebeltel, Olivier"},{"full_name":"Maler, Oded","first_name":"Oded","last_name":"Maler"},{"id":"40960E6E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5199-3143","full_name":"Ferrere, Thomas","first_name":"Thomas","last_name":"Ferrere"},{"full_name":"Ulus, Dogan","first_name":"Dogan","last_name":"Ulus"}],"issue":"6","volume":22,"doi":"10.1007/s10009-020-00582-z","day":"03","abstract":[{"lang":"eng","text":"We introduce in this paper AMT2.0, a tool for qualitative and quantitative analysis of hybrid continuous and Boolean signals that combine numerical values and discrete events. The evaluation of the signals is based on rich temporal specifications expressed in extended signal temporal logic, which integrates timed regular expressions within signal temporal logic. The tool features qualitative monitoring (property satisfaction checking), trace diagnostics for explaining and justifying property violations and specification-driven measurement of quantitative features of the signal. We demonstrate the tool functionality on several running examples and case studies, and evaluate its performance."}],"date_updated":"2023-09-08T11:52:02Z","year":"2020","citation":{"ama":"Nickovic D, Lebeltel O, Maler O, Ferrere T, Ulus D. AMT 2.0: Qualitative and quantitative trace analysis with extended signal temporal logic. <i>International Journal on Software Tools for Technology Transfer</i>. 2020;22(6):741-758. doi:<a href=\"https://doi.org/10.1007/s10009-020-00582-z\">10.1007/s10009-020-00582-z</a>","apa":"Nickovic, D., Lebeltel, O., Maler, O., Ferrere, T., &#38; Ulus, D. (2020). AMT 2.0: Qualitative and quantitative trace analysis with extended signal temporal logic. <i>International Journal on Software Tools for Technology Transfer</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s10009-020-00582-z\">https://doi.org/10.1007/s10009-020-00582-z</a>","ieee":"D. Nickovic, O. Lebeltel, O. Maler, T. Ferrere, and D. Ulus, “AMT 2.0: Qualitative and quantitative trace analysis with extended signal temporal logic,” <i>International Journal on Software Tools for Technology Transfer</i>, vol. 22, no. 6. Springer Nature, pp. 741–758, 2020.","chicago":"Nickovic, Dejan, Olivier Lebeltel, Oded Maler, Thomas Ferrere, and Dogan Ulus. “AMT 2.0: Qualitative and Quantitative Trace Analysis with Extended Signal Temporal Logic.” <i>International Journal on Software Tools for Technology Transfer</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1007/s10009-020-00582-z\">https://doi.org/10.1007/s10009-020-00582-z</a>.","mla":"Nickovic, Dejan, et al. “AMT 2.0: Qualitative and Quantitative Trace Analysis with Extended Signal Temporal Logic.” <i>International Journal on Software Tools for Technology Transfer</i>, vol. 22, no. 6, Springer Nature, 2020, pp. 741–58, doi:<a href=\"https://doi.org/10.1007/s10009-020-00582-z\">10.1007/s10009-020-00582-z</a>.","short":"D. Nickovic, O. Lebeltel, O. Maler, T. Ferrere, D. Ulus, International Journal on Software Tools for Technology Transfer 22 (2020) 741–758.","ista":"Nickovic D, Lebeltel O, Maler O, Ferrere T, Ulus D. 2020. AMT 2.0: Qualitative and quantitative trace analysis with extended signal temporal logic. International Journal on Software Tools for Technology Transfer. 22(6), 741–758."},"isi":1,"external_id":{"isi":["000555398600001"]}},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2020-02-01T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["0929-5313"],"eissn":["1573-6873"]},"oa":1,"file":[{"file_size":1941355,"checksum":"036e9451d6cd0c190ad25791bf82393b","date_created":"2020-01-28T09:31:09Z","file_name":"10827_2020_740_MOESM1_ESM.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:47:56Z","relation":"supplementary_material","access_level":"open_access","creator":"rcubero","file_id":"7380"},{"date_created":"2020-01-28T09:31:09Z","file_size":3257880,"checksum":"4dd8b1fd4b54486f79d82ac7b2a412b2","date_updated":"2020-07-14T12:47:56Z","file_name":"Cubero2020_Article_MultiscaleRelevanceAndInformat.pdf","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_id":"7381","creator":"rcubero"}],"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication":"Journal of Computational Neuroscience","has_accepted_license":"1","oa_version":"Published Version","project":[{"grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"month":"02","language":[{"iso":"eng"}],"keyword":["Time series analysis","Multiple time scale analysis","Spike train data","Information theory","Bayesian decoding"],"date_updated":"2023-08-17T14:35:22Z","year":"2020","citation":{"ista":"Cubero RJ, Marsili M, Roudi Y. 2020. Multiscale relevance and informative encoding in neuronal spike trains. Journal of Computational Neuroscience. 48, 85–102.","short":"R.J. Cubero, M. Marsili, Y. Roudi, Journal of Computational Neuroscience 48 (2020) 85–102.","mla":"Cubero, Ryan J., et al. “Multiscale Relevance and Informative Encoding in Neuronal Spike Trains.” <i>Journal of Computational Neuroscience</i>, vol. 48, Springer Nature, 2020, pp. 85–102, doi:<a href=\"https://doi.org/10.1007/s10827-020-00740-x\">10.1007/s10827-020-00740-x</a>.","ieee":"R. J. Cubero, M. Marsili, and Y. Roudi, “Multiscale relevance and informative encoding in neuronal spike trains,” <i>Journal of Computational Neuroscience</i>, vol. 48. Springer Nature, pp. 85–102, 2020.","chicago":"Cubero, Ryan J, Matteo Marsili, and Yasser Roudi. “Multiscale Relevance and Informative Encoding in Neuronal Spike Trains.” <i>Journal of Computational Neuroscience</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1007/s10827-020-00740-x\">https://doi.org/10.1007/s10827-020-00740-x</a>.","ama":"Cubero RJ, Marsili M, Roudi Y. Multiscale relevance and informative encoding in neuronal spike trains. <i>Journal of Computational Neuroscience</i>. 2020;48:85-102. doi:<a href=\"https://doi.org/10.1007/s10827-020-00740-x\">10.1007/s10827-020-00740-x</a>","apa":"Cubero, R. J., Marsili, M., &#38; Roudi, Y. (2020). Multiscale relevance and informative encoding in neuronal spike trains. <i>Journal of Computational Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s10827-020-00740-x\">https://doi.org/10.1007/s10827-020-00740-x</a>"},"isi":1,"external_id":{"isi":["000515321800006"]},"doi":"10.1007/s10827-020-00740-x","day":"01","abstract":[{"lang":"eng","text":"Neuronal responses to complex stimuli and tasks can encompass a wide range of time scales. Understanding these responses requires measures that characterize how the information on these response patterns are represented across multiple temporal resolutions. In this paper we propose a metric – which we call multiscale relevance (MSR) – to capture the dynamical variability of the activity of single neurons across different time scales. The MSR is a non-parametric, fully featureless indicator in that it uses only the time stamps of the firing activity without resorting to any a priori covariate or invoking any specific structure in the tuning curve for neural activity. When applied to neural data from the mEC and from the ADn and PoS regions of freely-behaving rodents, we found that neurons having low MSR tend to have low mutual information and low firing sparsity across the correlates that are believed to be encoded by the region of the brain where the recordings were made. In addition, neurons with high MSR contain significant information on spatial navigation and allow to decode spatial position or head direction as efficiently as those neurons whose firing activity has high mutual information with the covariate to be decoded and significantly better than the set of neurons with high local variations in their interspike intervals. Given these results, we propose that the MSR can be used as a measure to rank and select neurons for their information content without the need to appeal to any a priori covariate."}],"volume":48,"acknowledgement":"This research was supported by the Kavli Foundation and the Centre of Excellence scheme of the Research Council of Norway (Centre for Neural Computation). RJC is currently receiving funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 754411.","ddc":["004","519","570"],"_id":"7369","scopus_import":"1","author":[{"id":"850B2E12-9CD4-11E9-837F-E719E6697425","orcid":"0000-0003-0002-1867","full_name":"Cubero, Ryan J","first_name":"Ryan J","last_name":"Cubero"},{"full_name":"Marsili, Matteo","last_name":"Marsili","first_name":"Matteo"},{"first_name":"Yasser","last_name":"Roudi","full_name":"Roudi, Yasser"}],"publication_status":"published","article_processing_charge":"Yes (via OA deal)","department":[{"_id":"SaSi"}],"date_created":"2020-01-28T10:34:00Z","title":"Multiscale relevance and informative encoding in neuronal spike trains","intvolume":"        48","page":"85-102","ec_funded":1,"quality_controlled":"1","file_date_updated":"2020-07-14T12:47:56Z","publisher":"Springer Nature","article_type":"original"},{"type":"dissertation","date_published":"2019-05-23T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"supervisor":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik"}],"publication_identifier":{"issn":["2663-337X"]},"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"record":[{"relation":"dissertation_contains","id":"6900","status":"public"},{"status":"public","relation":"dissertation_contains","id":"281"},{"relation":"dissertation_contains","id":"2016","status":"public"},{"status":"public","relation":"dissertation_contains","id":"1576"}]},"file":[{"file_id":"6480","creator":"scepeda","relation":"source_file","access_level":"closed","date_updated":"2020-07-14T12:47:31Z","file_name":"Thesis_Cepeda.zip","content_type":"application/zip","date_created":"2019-05-23T11:18:16Z","file_size":23937464,"checksum":"75f9184c1346e10a5de5f9cc7338309a"},{"creator":"scepeda","file_id":"6481","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_name":"CepedaThesis.pdf","date_updated":"2020-07-14T12:47:31Z","checksum":"afdc0633ddbd71d5b13550d7fb4f4454","file_size":16646985,"date_created":"2019-05-23T11:18:13Z"}],"has_accepted_license":"1","month":"05","oa_version":"Published Version","keyword":["Information estimation","Time-series","data analysis"],"language":[{"iso":"eng"}],"year":"2019","citation":{"chicago":"Cepeda Humerez, Sarah A. “Estimating Information Flow in Single Cells.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6473\">https://doi.org/10.15479/AT:ISTA:6473</a>.","ieee":"S. A. Cepeda Humerez, “Estimating information flow in single cells,” Institute of Science and Technology Austria, 2019.","apa":"Cepeda Humerez, S. A. (2019). <i>Estimating information flow in single cells</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6473\">https://doi.org/10.15479/AT:ISTA:6473</a>","ama":"Cepeda Humerez SA. Estimating information flow in single cells. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6473\">10.15479/AT:ISTA:6473</a>","ista":"Cepeda Humerez SA. 2019. Estimating information flow in single cells. Institute of Science and Technology Austria.","mla":"Cepeda Humerez, Sarah A. <i>Estimating Information Flow in Single Cells</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6473\">10.15479/AT:ISTA:6473</a>.","short":"S.A. Cepeda Humerez, Estimating Information Flow in Single Cells, Institute of Science and Technology Austria, 2019."},"date_updated":"2025-05-28T11:57:00Z","abstract":[{"text":"Single cells are constantly interacting with their environment and each other, more importantly, the accurate perception of environmental cues is crucial for growth, survival, and reproduction. This communication between cells and their environment can be formalized in mathematical terms and be quantified as the information flow between them, as prescribed by information theory. \r\nThe recent availability of real–time dynamical patterns of signaling molecules in single cells has allowed us to identify encoding about the identity of the environment in the time–series. However, efficient estimation of the information transmitted by these signals has been a data–analysis challenge due to the high dimensionality of the trajectories and the limited number of samples. In the first part of this thesis, we develop and evaluate decoding–based estimation methods to lower bound the mutual information and derive model–based precise information estimates for biological reaction networks governed by the chemical master equation. This is followed by applying the decoding-based methods to study the intracellular representation of extracellular changes in budding yeast, by observing the transient dynamics of nuclear translocation of 10 transcription factors in response to 3 stress conditions. Additionally, we apply these estimators to previously published data on ERK and Ca2+ signaling and yeast stress response. We argue that this single cell decoding-based measure of information provides an unbiased, quantitative and interpretable measure for the fidelity of biological signaling processes. \r\nFinally, in the last section, we deal with gene regulation which is primarily controlled by transcription factors (TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate TFs activate transcription diminishes the accuracy of regulation with potentially disastrous effects for the cell. This ’crosstalk’ acts as a previously unexplored source of noise in biochemical networks and puts a strong constraint on their performance. To mitigate erroneous initiation we propose an out of equilibrium scheme that implements kinetic proofreading. We show that such architectures are favored  over their equilibrium counterparts for complex organisms despite introducing noise in gene expression. ","lang":"eng"}],"day":"23","doi":"10.15479/AT:ISTA:6473","degree_awarded":"PhD","ddc":["004"],"author":[{"id":"3DEE19A4-F248-11E8-B48F-1D18A9856A87","full_name":"Cepeda Humerez, Sarah A","last_name":"Cepeda Humerez","first_name":"Sarah A"}],"_id":"6473","title":"Estimating information flow in single cells","alternative_title":["ISTA Thesis"],"article_processing_charge":"No","date_created":"2019-05-21T00:11:23Z","department":[{"_id":"GaTk"}],"publication_status":"published","file_date_updated":"2020-07-14T12:47:31Z","page":"135","publisher":"Institute of Science and Technology Austria"}]