[{"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","main_file_link":[{"url":"https://doi.org/10.1038/s41592-022-01444-z","open_access":"1"}],"date_published":"2022-04-08T00:00:00Z","type":"journal_article","oa":1,"publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"language":[{"iso":"eng"}],"publication":"Nature Methods","month":"04","oa_version":"Published Version","project":[{"_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209"}],"acknowledgement":"Our paper is dedicated to all freedom-loving people around the world, and to the people of Ukraine who fight for our freedom. We thank William M. Switzer and Ellsworth M. Campbell from the Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA, for discussions and suggestions. We thank Jason Ladner from the Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, for providing suggestions and feedback. S.M. was partially supported by National Science Foundation grants 2041984. T.L. is supported by the NSFC Excellent Young Scientists Fund (Hong Kong and Macau; 31922087), Research Grants Council (RGC) Collaborative Research Fund (C7144-20GF), RGC Research Impact Fund (R7021-20), Innovation and Technology Commission’s InnoHK funding (D24H) and Health and Medical Research Fund (COVID190223). P.S. was supported by US National Institutes of Health (NIH) grant 1R01EB025022 and National Science Foundation (NSF) grant 2047828. M.A. acknowledges King Abdulaziz City for Science and Technology and the Saudi Human Genome Project for technical and financial support (https://shgp.kacst.edu.sa) N.W. was supported by US NIH grants R00 AI139445, DP2 AT011966 and R01 AI167910. A.S. acknowledge funding from NSF grant no. 2029025. A.Z. has been partially supported by NIH grants 1R01EB025022-01 and 1R21CA241044-01A1. S. Knyazev has been partly supported by Molecular Basis of Disease at Georgia State University and NIH awards R01 HG009120, R01 MH115676, R01 AI153827 and U01 HG011715. A.W. has been supported by the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-061). R.K. was supported by NSF project 2038509, RAPID: Improving QIIME 2 and UniFrac for Viruses to Respond to COVID-19, CDC project 30055281 with Scripps led by Kristian Andersen, Genomic sequencing of SARS-CoV-2 to investigate local and cross-border emergence and spread. J.O.W. was supported by NIH–National Institute of Allergy and Infectious Diseases (NIAID) R01 AI135992 and receives funding from the CDC unrelated to this work. T.I.V. is supported by the Branco Weiss Fellowship. Y.P. was supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare” N◦075-15-2020-926. E.B. was supported by a US National Institute of General Medical Sciences IDeA Alaska INBRE (P20GM103395) and NIAID CEIRR (75N93019R00028). C.E.M. thanks Testing for America (501c3), OpenCovidScreen Foundation, Igor Tulchinsky and the WorldQuant Foundation, Bill Ackman and Olivia Flatto and the Pershing Square Foundation, Ken Griffin and Citadel, the US National Institutes of Health (R01AI125416, R01AI151059, R21AI129851, U01DA053941), and the Alfred P. Sloan Foundation (G-2015-13964). C.Y.C. is supported by US CDC Epidemiology and Laboratory Capacity (ELC) for Infectious Diseases grant 6NU50CK000539 to the California Department of Public Health, the Innovative Genomics Institute (IGI) at the University of California, Berkeley, and University of California, San Francisco, NIH grant R33AI12945 and US CDC contract 75D30121C10991. A.K. was partly supported by RFBR grant 20-515-80017. P.L. acknowledges support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. ~725422 - ReservoirDOCS), the Wellcome Trust through project 206298/Z/17/Z (Artic Network) and NIH grants R01 AI153044 and U19 AI135995. K.C. acknowledges support from the US NSF award EEID-IOS-2109688. F.K.’s work was supported by an ERC Consolidator grant to F.K. (771209–CharFL).","volume":19,"isi":1,"external_id":{"isi":["000781199600011"],"pmid":["35396471"]},"date_updated":"2023-08-03T06:46:09Z","year":"2022","citation":{"short":"S. Knyazev, K. Chhugani, V. Sarwal, R. Ayyala, H. Singh, S. Karthikeyan, D. Deshpande, P.I. Baykal, Z. Comarova, A. Lu, Y. Porozov, T.I. Vasylyeva, J.O. Wertheim, B.T. Tierney, C.Y. Chiu, R. Sun, A. Wu, M.S. Abedalthagafi, V.M. Pak, S.H. Nagaraj, A.L. Smith, P. Skums, B. Pasaniuc, A. Komissarov, C.E. Mason, E. Bortz, P. Lemey, F. Kondrashov, N. Beerenwinkel, T.T.Y. Lam, N.C. Wu, A. Zelikovsky, R. Knight, K.A. Crandall, S. Mangul, Nature Methods 19 (2022) 374–380.","mla":"Knyazev, Sergey, et al. “Unlocking Capacities of Genomics for the COVID-19 Response and Future Pandemics.” <i>Nature Methods</i>, vol. 19, no. 4, Springer Nature, 2022, pp. 374–80, doi:<a href=\"https://doi.org/10.1038/s41592-022-01444-z\">10.1038/s41592-022-01444-z</a>.","ista":"Knyazev S, Chhugani K, Sarwal V, Ayyala R, Singh H, Karthikeyan S, Deshpande D, Baykal PI, Comarova Z, Lu A, Porozov Y, Vasylyeva TI, Wertheim JO, Tierney BT, Chiu CY, Sun R, Wu A, Abedalthagafi MS, Pak VM, Nagaraj SH, Smith AL, Skums P, Pasaniuc B, Komissarov A, Mason CE, Bortz E, Lemey P, Kondrashov F, Beerenwinkel N, Lam TTY, Wu NC, Zelikovsky A, Knight R, Crandall KA, Mangul S. 2022. Unlocking capacities of genomics for the COVID-19 response and future pandemics. Nature Methods. 19(4), 374–380.","apa":"Knyazev, S., Chhugani, K., Sarwal, V., Ayyala, R., Singh, H., Karthikeyan, S., … Mangul, S. (2022). Unlocking capacities of genomics for the COVID-19 response and future pandemics. <i>Nature Methods</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41592-022-01444-z\">https://doi.org/10.1038/s41592-022-01444-z</a>","ama":"Knyazev S, Chhugani K, Sarwal V, et al. Unlocking capacities of genomics for the COVID-19 response and future pandemics. <i>Nature Methods</i>. 2022;19(4):374-380. doi:<a href=\"https://doi.org/10.1038/s41592-022-01444-z\">10.1038/s41592-022-01444-z</a>","ieee":"S. Knyazev <i>et al.</i>, “Unlocking capacities of genomics for the COVID-19 response and future pandemics,” <i>Nature Methods</i>, vol. 19, no. 4. Springer Nature, pp. 374–380, 2022.","chicago":"Knyazev, Sergey, Karishma Chhugani, Varuni Sarwal, Ram Ayyala, Harman Singh, Smruthi Karthikeyan, Dhrithi Deshpande, et al. “Unlocking Capacities of Genomics for the COVID-19 Response and Future Pandemics.” <i>Nature Methods</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41592-022-01444-z\">https://doi.org/10.1038/s41592-022-01444-z</a>."},"abstract":[{"text":"During the COVID-19 pandemic, genomics and bioinformatics have emerged as essential public health tools. The genomic data acquired using these methods have supported the global health response, facilitated the development of testing methods and allowed the timely tracking of novel SARS-CoV-2 variants. Yet the virtually unlimited potential for rapid generation and analysis of genomic data is also coupled with unique technical, scientific and organizational challenges. Here, we discuss the application of genomic and computational methods for efficient data-driven COVID-19 response, the advantages of the democratization of viral sequencing around the world and the challenges associated with viral genome data collection and processing.","lang":"eng"}],"doi":"10.1038/s41592-022-01444-z","day":"08","page":"374-380","quality_controlled":"1","ec_funded":1,"article_type":"letter_note","publisher":"Springer Nature","author":[{"full_name":"Knyazev, Sergey","last_name":"Knyazev","first_name":"Sergey"},{"full_name":"Chhugani, Karishma","last_name":"Chhugani","first_name":"Karishma"},{"full_name":"Sarwal, Varuni","last_name":"Sarwal","first_name":"Varuni"},{"last_name":"Ayyala","first_name":"Ram","full_name":"Ayyala, Ram"},{"last_name":"Singh","first_name":"Harman","full_name":"Singh, Harman"},{"full_name":"Karthikeyan, Smruthi","first_name":"Smruthi","last_name":"Karthikeyan"},{"full_name":"Deshpande, Dhrithi","first_name":"Dhrithi","last_name":"Deshpande"},{"last_name":"Baykal","first_name":"Pelin Icer","full_name":"Baykal, Pelin Icer"},{"full_name":"Comarova, Zoia","first_name":"Zoia","last_name":"Comarova"},{"first_name":"Angela","last_name":"Lu","full_name":"Lu, Angela"},{"full_name":"Porozov, Yuri","last_name":"Porozov","first_name":"Yuri"},{"full_name":"Vasylyeva, Tetyana I.","last_name":"Vasylyeva","first_name":"Tetyana I."},{"last_name":"Wertheim","first_name":"Joel O.","full_name":"Wertheim, Joel O."},{"full_name":"Tierney, Braden T.","first_name":"Braden T.","last_name":"Tierney"},{"first_name":"Charles Y.","last_name":"Chiu","full_name":"Chiu, Charles Y."},{"first_name":"Ren","last_name":"Sun","full_name":"Sun, Ren"},{"first_name":"Aiping","last_name":"Wu","full_name":"Wu, Aiping"},{"full_name":"Abedalthagafi, Malak S.","first_name":"Malak S.","last_name":"Abedalthagafi"},{"full_name":"Pak, Victoria M.","first_name":"Victoria M.","last_name":"Pak"},{"first_name":"Shivashankar H.","last_name":"Nagaraj","full_name":"Nagaraj, Shivashankar H."},{"full_name":"Smith, Adam L.","last_name":"Smith","first_name":"Adam L."},{"first_name":"Pavel","last_name":"Skums","full_name":"Skums, Pavel"},{"first_name":"Bogdan","last_name":"Pasaniuc","full_name":"Pasaniuc, Bogdan"},{"first_name":"Andrey","last_name":"Komissarov","full_name":"Komissarov, Andrey"},{"full_name":"Mason, Christopher E.","last_name":"Mason","first_name":"Christopher E."},{"first_name":"Eric","last_name":"Bortz","full_name":"Bortz, Eric"},{"last_name":"Lemey","first_name":"Philippe","full_name":"Lemey, Philippe"},{"id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","last_name":"Kondrashov","first_name":"Fyodor"},{"first_name":"Niko","last_name":"Beerenwinkel","full_name":"Beerenwinkel, Niko"},{"first_name":"Tommy Tsan Yuk","last_name":"Lam","full_name":"Lam, Tommy Tsan Yuk"},{"full_name":"Wu, Nicholas C.","last_name":"Wu","first_name":"Nicholas C."},{"first_name":"Alex","last_name":"Zelikovsky","full_name":"Zelikovsky, Alex"},{"full_name":"Knight, Rob","first_name":"Rob","last_name":"Knight"},{"full_name":"Crandall, Keith A.","first_name":"Keith A.","last_name":"Crandall"},{"first_name":"Serghei","last_name":"Mangul","full_name":"Mangul, Serghei"}],"issue":"4","pmid":1,"_id":"11187","scopus_import":"1","title":"Unlocking capacities of genomics for the COVID-19 response and future pandemics","intvolume":"        19","publication_status":"published","department":[{"_id":"FyKo"}],"date_created":"2022-04-17T22:01:48Z","article_processing_charge":"No"},{"file":[{"access_level":"open_access","relation":"main_file","success":1,"creator":"dernst","file_id":"11455","file_size":463025,"checksum":"05a1fe7d10914a00c2bca9b447993a65","date_created":"2022-06-20T07:51:32Z","content_type":"application/pdf","file_name":"2022_BulletinMathBiology_Saona.pdf","date_updated":"2022-06-20T07:51:32Z"}],"status":"public","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1007/s11538-022-01118-z"}]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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":"2022-06-17T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["0092-8240"],"eissn":["1522-9602"]},"oa":1,"language":[{"iso":"eng"}],"keyword":["Computational Theory and Mathematics","General Agricultural and Biological Sciences","Pharmacology","General Environmental Science","General Biochemistry","Genetics and Molecular Biology","General Mathematics","Immunology","General Neuroscience"],"publication":"Bulletin of Mathematical Biology","has_accepted_license":"1","oa_version":"Published Version","project":[{"call_identifier":"H2020","_id":"26580278-B435-11E9-9278-68D0E5697425","name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209"},{"_id":"c098eddd-5a5b-11eb-8a69-abe27170a68f","name":"Evolutionary analysis of gene regulation","grant_number":"I05127"}],"month":"06","article_number":"74","acknowledgement":"We are grateful to Herbert Edelsbrunner and Jeferson Zapata for helpful discussions. Open access funding provided by Austrian Science Fund (FWF). Partially supported by the ERC Consolidator (771209–CharFL) and the FWF Austrian Science Fund (I5127-B) grants to FAK.","volume":84,"ddc":["510","570"],"date_updated":"2023-08-03T07:20:53Z","year":"2022","citation":{"mla":"Saona Urmeneta, Raimundo J., et al. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8, 74, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>.","short":"R.J. Saona Urmeneta, F. Kondrashov, K. Khudiakova, Bulletin of Mathematical Biology 84 (2022).","ista":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. 2022. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 84(8), 74.","ama":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. 2022;84(8). doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>","apa":"Saona Urmeneta, R. J., Kondrashov, F., &#38; Khudiakova, K. (2022). Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>","ieee":"R. J. Saona Urmeneta, F. Kondrashov, and K. Khudiakova, “Relation between the number of peaks and the number of reciprocal sign epistatic interactions,” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8. Springer Nature, 2022.","chicago":"Saona Urmeneta, Raimundo J, Fyodor Kondrashov, and Kseniia Khudiakova. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>."},"isi":1,"external_id":{"isi":["000812509800001"]},"doi":"10.1007/s11538-022-01029-z","day":"17","abstract":[{"text":"Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks.","lang":"eng"}],"quality_controlled":"1","ec_funded":1,"file_date_updated":"2022-06-20T07:51:32Z","publisher":"Springer Nature","article_type":"original","_id":"11447","scopus_import":"1","author":[{"last_name":"Saona Urmeneta","first_name":"Raimundo J","full_name":"Saona Urmeneta, Raimundo J","orcid":"0000-0001-5103-038X","id":"BD1DF4C4-D767-11E9-B658-BC13E6697425"},{"orcid":"0000-0001-8243-4694","full_name":"Kondrashov, Fyodor","first_name":"Fyodor","last_name":"Kondrashov","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"},{"id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","orcid":"0000-0002-6246-1465","full_name":"Khudiakova, Kseniia","first_name":"Kseniia","last_name":"Khudiakova"}],"issue":"8","publication_status":"published","department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"JaMa"}],"date_created":"2022-06-17T16:16:15Z","article_processing_charge":"Yes (via OA deal)","title":"Relation between the number of peaks and the number of reciprocal sign epistatic interactions","intvolume":"        84"},{"file":[{"creator":"dernst","file_id":"11454","access_level":"open_access","relation":"main_file","success":1,"content_type":"application/pdf","file_name":"2022_eLife_Somermeyer.pdf","date_updated":"2022-06-20T07:44:19Z","checksum":"7573c28f44028ab0cc81faef30039e44","file_size":5297213,"date_created":"2022-06-20T07:44:19Z"}],"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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":"2022-05-05T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["2050-084X"]},"oa":1,"language":[{"iso":"eng"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"publication":"eLife","has_accepted_license":"1","oa_version":"Published Version","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"project":[{"call_identifier":"H2020","_id":"26580278-B435-11E9-9278-68D0E5697425","name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209"},{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"month":"05","article_number":"75842","acknowledgement":"We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova for technical assistance and data interpretation. Core facility Biomolecular Interactions and Crystallization of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this paper. This research was supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF). MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC), Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility in the Vanderbilt University Center for Structural Biology. We are grateful to Joel M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4, the Imperial College Research Fellowship and the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\"). Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH). This work was supported by a Russian Science Foundation grant 19-74-10102.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385.","volume":11,"ddc":["570"],"date_updated":"2023-08-03T07:20:15Z","citation":{"ama":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>","apa":"Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>","ieee":"L. Gonzalez Somermeyer <i>et al.</i>, “Heterogeneity of the GFP fitness landscape and data-driven protein design,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","chicago":"Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>.","short":"L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022).","mla":"Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>, vol. 11, 75842, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>.","ista":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842."},"year":"2022","isi":1,"external_id":{"isi":["000799197200001"]},"doi":"10.7554/elife.75842","day":"05","abstract":[{"lang":"eng","text":"Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering."}],"quality_controlled":"1","ec_funded":1,"file_date_updated":"2022-06-20T07:44:19Z","publisher":"eLife Sciences Publications","article_type":"original","_id":"11448","scopus_import":"1","author":[{"full_name":"Gonzalez Somermeyer, Louisa","orcid":"0000-0001-9139-5383","last_name":"Gonzalez Somermeyer","first_name":"Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Fleiss","first_name":"Aubin","full_name":"Fleiss, Aubin"},{"full_name":"Mishin, Alexander S","first_name":"Alexander S","last_name":"Mishin"},{"first_name":"Nina G","last_name":"Bozhanova","full_name":"Bozhanova, Nina G"},{"last_name":"Igolkina","first_name":"Anna A","full_name":"Igolkina, Anna A"},{"last_name":"Meiler","first_name":"Jens","full_name":"Meiler, Jens"},{"full_name":"Alaball Pujol, Maria-Elisenda","first_name":"Maria-Elisenda","last_name":"Alaball Pujol"},{"last_name":"Putintseva","first_name":"Ekaterina V","full_name":"Putintseva, Ekaterina V"},{"first_name":"Karen S","last_name":"Sarkisyan","full_name":"Sarkisyan, Karen S"},{"id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor","last_name":"Kondrashov","orcid":"0000-0001-8243-4694","full_name":"Kondrashov, Fyodor"}],"publication_status":"published","department":[{"_id":"GradSch"},{"_id":"FyKo"}],"article_processing_charge":"No","date_created":"2022-06-18T09:06:59Z","title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","intvolume":"        11"},{"ddc":["570","610"],"acknowledgement":"We thank Alexey Kondrashov, Nick Machnik, Raimundo Julian Saona Urmeneta, Gasper Tkacik and Nick Barton for fruitful discussions. We also thank participants of EvoLunch seminar at IST Austria and the internal seminar at the Banco de España for useful comments. The opinions expressed in this document are exclusively of the authors and, therefore, do not necessarily coincide with those of the Banco de España or the Eurosystem. ETD is supported by the Swiss National Science and Louis Jeantet Foundation. The work of FAK was in part supported by the ERC Consolidator Grant (771209-CharFL).","volume":11,"abstract":[{"text":"Vaccines are thought to be the best available solution for controlling the ongoing SARS-CoV-2 pandemic. However, the emergence of vaccine-resistant strains may come too rapidly for current vaccine developments to alleviate the health, economic and social consequences of the pandemic. To quantify and characterize the risk of such a scenario, we created a SIR-derived model with initial stochastic dynamics of the vaccine-resistant strain to study the probability of its emergence and establishment. Using parameters realistically resembling SARS-CoV-2 transmission, we model a wave-like pattern of the pandemic and consider the impact of the rate of vaccination and the strength of non-pharmaceutical intervention measures on the probability of emergence of a resistant strain. As expected, we found that a fast rate of vaccination decreases the probability of emergence of a resistant strain. Counterintuitively, when a relaxation of non-pharmaceutical interventions happened at a time when most individuals of the population have already been vaccinated the probability of emergence of a resistant strain was greatly increased. Consequently, we show that a period of transmission reduction close to the end of the vaccination campaign can substantially reduce the probability of resistant strain establishment. Our results suggest that policymakers and individuals should consider maintaining non-pharmaceutical interventions and transmission-reducing behaviours throughout the entire vaccination period.","lang":"eng"}],"day":"30","doi":"10.1038/s41598-021-95025-3","external_id":{"pmid":["34330988"],"isi":["000683329100001"]},"isi":1,"citation":{"chicago":"Rella, Simon, Yuliya A. Kulikova, Emmanouil T. Dermitzakis, and Fyodor Kondrashov. “Rates of SARS-CoV-2 Transmission and Vaccination Impact the Fate of Vaccine-Resistant Strains.” <i>Scientific Reports</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41598-021-95025-3\">https://doi.org/10.1038/s41598-021-95025-3</a>.","ieee":"S. Rella, Y. A. Kulikova, E. T. Dermitzakis, and F. Kondrashov, “Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains,” <i>Scientific Reports</i>, vol. 11, no. 1. Springer Nature, 2021.","ama":"Rella S, Kulikova YA, Dermitzakis ET, Kondrashov F. Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains. <i>Scientific Reports</i>. 2021;11(1). doi:<a href=\"https://doi.org/10.1038/s41598-021-95025-3\">10.1038/s41598-021-95025-3</a>","apa":"Rella, S., Kulikova, Y. A., Dermitzakis, E. T., &#38; Kondrashov, F. (2021). Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains. <i>Scientific Reports</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41598-021-95025-3\">https://doi.org/10.1038/s41598-021-95025-3</a>","ista":"Rella S, Kulikova YA, Dermitzakis ET, Kondrashov F. 2021. Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains. Scientific Reports. 11(1), 15729.","mla":"Rella, Simon, et al. “Rates of SARS-CoV-2 Transmission and Vaccination Impact the Fate of Vaccine-Resistant Strains.” <i>Scientific Reports</i>, vol. 11, no. 1, 15729, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41598-021-95025-3\">10.1038/s41598-021-95025-3</a>.","short":"S. Rella, Y.A. Kulikova, E.T. Dermitzakis, F. Kondrashov, Scientific Reports 11 (2021)."},"year":"2021","date_updated":"2023-08-11T10:42:58Z","article_type":"original","publisher":"Springer Nature","file_date_updated":"2021-08-16T11:36:49Z","quality_controlled":"1","ec_funded":1,"intvolume":"        11","title":"Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains","department":[{"_id":"FyKo"}],"date_created":"2021-08-15T22:01:26Z","article_processing_charge":"Yes","publication_status":"published","issue":"1","author":[{"full_name":"Rella, Simon","last_name":"Rella","first_name":"Simon","id":"B4765ACA-AA38-11E9-AC9A-0930E6697425"},{"full_name":"Kulikova, Yuliya A.","last_name":"Kulikova","first_name":"Yuliya A."},{"last_name":"Dermitzakis","first_name":"Emmanouil T.","full_name":"Dermitzakis, Emmanouil T."},{"last_name":"Kondrashov","first_name":"Fyodor","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","_id":"9905","pmid":1,"related_material":{"link":[{"relation":"press_release","description":"News on IST Website","url":"https://ist.ac.at/en/news/counterintuitive-dynamics-threaten-the-end-of-the-pandemic/"}]},"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"file_id":"9927","creator":"asandaue","success":1,"access_level":"open_access","relation":"main_file","date_updated":"2021-08-16T11:36:49Z","content_type":"application/pdf","file_name":"2021_ScientificReports_Rella.pdf","date_created":"2021-08-16T11:36:49Z","checksum":"ac86892ed17e6724c7251844da5cef5c","file_size":3432001}],"oa":1,"publication_identifier":{"eissn":["20452322"]},"type":"journal_article","date_published":"2021-07-30T00:00:00Z","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)"},"language":[{"iso":"eng"}],"article_number":"15729","month":"07","project":[{"name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209","_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"oa_version":"Published Version","has_accepted_license":"1","publication":"Scientific Reports"},{"scopus_import":"1","pmid":1,"_id":"9910","issue":"7","author":[{"last_name":"Slavskii","first_name":"Sergei A.","full_name":"Slavskii, Sergei A."},{"last_name":"Kuznetsov","first_name":"Ivan A.","full_name":"Kuznetsov, Ivan A."},{"full_name":"Shashkova, Tatiana I.","last_name":"Shashkova","first_name":"Tatiana I."},{"full_name":"Bazykin, Georgii A.","first_name":"Georgii A.","last_name":"Bazykin"},{"full_name":"Axenovich, Tatiana I.","last_name":"Axenovich","first_name":"Tatiana I."},{"last_name":"Kondrashov","first_name":"Fyodor","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Yurii S.","last_name":"Aulchenko","full_name":"Aulchenko, Yurii S."}],"article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"FyKo"}],"date_created":"2021-08-15T22:01:28Z","publication_status":"published","intvolume":"        29","title":"The limits of normal approximation for adult height","ec_funded":1,"quality_controlled":"1","page":"1082-1091","file_date_updated":"2021-08-16T09:14:36Z","publisher":"Springer Nature","article_type":"original","citation":{"chicago":"Slavskii, Sergei A., Ivan A. Kuznetsov, Tatiana I. Shashkova, Georgii A. Bazykin, Tatiana I. Axenovich, Fyodor Kondrashov, and Yurii S. Aulchenko. “The Limits of Normal Approximation for Adult Height.” <i>European Journal of Human Genetics</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41431-021-00836-7\">https://doi.org/10.1038/s41431-021-00836-7</a>.","ieee":"S. A. Slavskii <i>et al.</i>, “The limits of normal approximation for adult height,” <i>European Journal of Human Genetics</i>, vol. 29, no. 7. Springer Nature, pp. 1082–1091, 2021.","ama":"Slavskii SA, Kuznetsov IA, Shashkova TI, et al. The limits of normal approximation for adult height. <i>European Journal of Human Genetics</i>. 2021;29(7):1082-1091. doi:<a href=\"https://doi.org/10.1038/s41431-021-00836-7\">10.1038/s41431-021-00836-7</a>","apa":"Slavskii, S. A., Kuznetsov, I. A., Shashkova, T. I., Bazykin, G. A., Axenovich, T. I., Kondrashov, F., &#38; Aulchenko, Y. S. (2021). The limits of normal approximation for adult height. <i>European Journal of Human Genetics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41431-021-00836-7\">https://doi.org/10.1038/s41431-021-00836-7</a>","ista":"Slavskii SA, Kuznetsov IA, Shashkova TI, Bazykin GA, Axenovich TI, Kondrashov F, Aulchenko YS. 2021. The limits of normal approximation for adult height. European Journal of Human Genetics. 29(7), 1082–1091.","mla":"Slavskii, Sergei A., et al. “The Limits of Normal Approximation for Adult Height.” <i>European Journal of Human Genetics</i>, vol. 29, no. 7, Springer Nature, 2021, pp. 1082–91, doi:<a href=\"https://doi.org/10.1038/s41431-021-00836-7\">10.1038/s41431-021-00836-7</a>.","short":"S.A. Slavskii, I.A. Kuznetsov, T.I. Shashkova, G.A. Bazykin, T.I. Axenovich, F. Kondrashov, Y.S. Aulchenko, European Journal of Human Genetics 29 (2021) 1082–1091."},"year":"2021","date_updated":"2023-08-11T10:33:42Z","external_id":{"pmid":["33664501"],"isi":["000625853200001"]},"isi":1,"day":"01","doi":"10.1038/s41431-021-00836-7","abstract":[{"lang":"eng","text":"Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait."}],"volume":29,"acknowledgement":"We are grateful to Marianna Bevova and Pavel Borodin for fruitful discussion and help with conceptualising our findings and to Lennart C. Karssen for help with handling the UK Biobank data.\r\n\r\nFunding\r\nThis research has been conducted using the UK Biobank Resource (project # 41601, “Non-additive effects in control of complex human traits”). The work of SAS, IAK, and TIS were supported by Russian Ministry of Science and Education under the 5–100 Excellence Programme. The work of YSA and TIA was supported by the Ministry of Education and Science of the RF via the Institute of Cytology and Genetics SB RAS (project number 0324-2019-0040-C-01/AAAA-A17-117092070032-4). FAK is supported by the ERC Consolidator Grant (ChrFL: 771209).","ddc":["576"],"has_accepted_license":"1","publication":"European Journal of Human Genetics","project":[{"grant_number":"771209","name":"Characterizing the fitness landscape on population and global scales","call_identifier":"H2020","_id":"26580278-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","month":"07","language":[{"iso":"eng"}],"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":"2021-07-01T00:00:00Z","publication_identifier":{"issn":["10184813"],"eissn":["14765438"]},"oa":1,"file":[{"creator":"asandaue","file_id":"9921","success":1,"relation":"main_file","access_level":"open_access","file_name":"2021_EuropeanJournalOfHumanGenetics_Slavskii.pdf","content_type":"application/pdf","date_updated":"2021-08-16T09:14:36Z","checksum":"a676d76f91b0dbe0504c63e469129c2a","file_size":1079395,"date_created":"2021-08-16T09:14:36Z"}],"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"scopus_import":"1","pmid":1,"_id":"7889","author":[{"last_name":"Mitiouchkina","first_name":"Tatiana","full_name":"Mitiouchkina, Tatiana"},{"full_name":"Mishin, Alexander S.","first_name":"Alexander S.","last_name":"Mishin"},{"id":"4720D23C-F248-11E8-B48F-1D18A9856A87","full_name":"Gonzalez Somermeyer, Louisa","orcid":"0000-0001-9139-5383","last_name":"Gonzalez Somermeyer","first_name":"Louisa"},{"last_name":"Markina","first_name":"Nadezhda M.","full_name":"Markina, Nadezhda M."},{"full_name":"Chepurnyh, Tatiana V.","last_name":"Chepurnyh","first_name":"Tatiana V."},{"first_name":"Elena B.","last_name":"Guglya","full_name":"Guglya, Elena B."},{"full_name":"Karataeva, Tatiana A.","last_name":"Karataeva","first_name":"Tatiana A."},{"full_name":"Palkina, Kseniia A.","last_name":"Palkina","first_name":"Kseniia A."},{"last_name":"Shakhova","first_name":"Ekaterina S.","full_name":"Shakhova, Ekaterina S."},{"first_name":"Liliia I.","last_name":"Fakhranurova","full_name":"Fakhranurova, Liliia I."},{"full_name":"Chekova, Sofia V.","last_name":"Chekova","first_name":"Sofia V."},{"full_name":"Tsarkova, Aleksandra S.","first_name":"Aleksandra S.","last_name":"Tsarkova"},{"full_name":"Golubev, Yaroslav V.","first_name":"Yaroslav V.","last_name":"Golubev"},{"last_name":"Negrebetsky","first_name":"Vadim V.","full_name":"Negrebetsky, Vadim V."},{"full_name":"Dolgushin, Sergey A.","last_name":"Dolgushin","first_name":"Sergey A."},{"full_name":"Shalaev, Pavel V.","last_name":"Shalaev","first_name":"Pavel V."},{"full_name":"Shlykov, Dmitry","last_name":"Shlykov","first_name":"Dmitry"},{"full_name":"Melnik, Olesya A.","first_name":"Olesya A.","last_name":"Melnik"},{"full_name":"Shipunova, Victoria O.","last_name":"Shipunova","first_name":"Victoria O."},{"full_name":"Deyev, Sergey M.","first_name":"Sergey M.","last_name":"Deyev"},{"first_name":"Andrey I.","last_name":"Bubyrev","full_name":"Bubyrev, Andrey I."},{"full_name":"Pushin, Alexander S.","first_name":"Alexander S.","last_name":"Pushin"},{"last_name":"Choob","first_name":"Vladimir V.","full_name":"Choob, Vladimir V."},{"full_name":"Dolgov, Sergey V.","last_name":"Dolgov","first_name":"Sergey V."},{"orcid":"0000-0001-8243-4694","full_name":"Kondrashov, Fyodor","first_name":"Fyodor","last_name":"Kondrashov","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ilia V.","last_name":"Yampolsky","full_name":"Yampolsky, Ilia V."},{"last_name":"Sarkisyan","first_name":"Karen S.","full_name":"Sarkisyan, Karen S."}],"date_created":"2020-05-25T15:02:00Z","article_processing_charge":"No","department":[{"_id":"FyKo"}],"publication_status":"published","intvolume":"        38","title":"Plants with genetically encoded autoluminescence","quality_controlled":"1","ec_funded":1,"page":"944-946","file_date_updated":"2021-03-02T23:30:03Z","publisher":"Springer Nature","article_type":"original","year":"2020","citation":{"chicago":"Mitiouchkina, Tatiana, Alexander S. Mishin, Louisa Gonzalez Somermeyer, Nadezhda M. Markina, Tatiana V. Chepurnyh, Elena B. Guglya, Tatiana A. Karataeva, et al. “Plants with Genetically Encoded Autoluminescence.” <i>Nature Biotechnology</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41587-020-0500-9\">https://doi.org/10.1038/s41587-020-0500-9</a>.","ieee":"T. Mitiouchkina <i>et al.</i>, “Plants with genetically encoded autoluminescence,” <i>Nature Biotechnology</i>, vol. 38. Springer Nature, pp. 944–946, 2020.","ama":"Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, et al. Plants with genetically encoded autoluminescence. <i>Nature Biotechnology</i>. 2020;38:944-946. doi:<a href=\"https://doi.org/10.1038/s41587-020-0500-9\">10.1038/s41587-020-0500-9</a>","apa":"Mitiouchkina, T., Mishin, A. S., Gonzalez Somermeyer, L., Markina, N. M., Chepurnyh, T. V., Guglya, E. B., … Sarkisyan, K. S. (2020). Plants with genetically encoded autoluminescence. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-020-0500-9\">https://doi.org/10.1038/s41587-020-0500-9</a>","ista":"Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, Markina NM, Chepurnyh TV, Guglya EB, Karataeva TA, Palkina KA, Shakhova ES, Fakhranurova LI, Chekova SV, Tsarkova AS, Golubev YV, Negrebetsky VV, Dolgushin SA, Shalaev PV, Shlykov D, Melnik OA, Shipunova VO, Deyev SM, Bubyrev AI, Pushin AS, Choob VV, Dolgov SV, Kondrashov F, Yampolsky IV, Sarkisyan KS. 2020. Plants with genetically encoded autoluminescence. Nature Biotechnology. 38, 944–946.","short":"T. Mitiouchkina, A.S. Mishin, L. Gonzalez Somermeyer, N.M. Markina, T.V. Chepurnyh, E.B. Guglya, T.A. Karataeva, K.A. Palkina, E.S. Shakhova, L.I. Fakhranurova, S.V. Chekova, A.S. Tsarkova, Y.V. Golubev, V.V. Negrebetsky, S.A. Dolgushin, P.V. Shalaev, D. Shlykov, O.A. Melnik, V.O. Shipunova, S.M. Deyev, A.I. Bubyrev, A.S. Pushin, V.V. Choob, S.V. Dolgov, F. Kondrashov, I.V. Yampolsky, K.S. Sarkisyan, Nature Biotechnology 38 (2020) 944–946.","mla":"Mitiouchkina, Tatiana, et al. “Plants with Genetically Encoded Autoluminescence.” <i>Nature Biotechnology</i>, vol. 38, Springer Nature, 2020, pp. 944–46, doi:<a href=\"https://doi.org/10.1038/s41587-020-0500-9\">10.1038/s41587-020-0500-9</a>."},"date_updated":"2023-09-05T15:30:34Z","external_id":{"isi":["000529298800003"],"pmid":["32341562"]},"isi":1,"day":"27","doi":"10.1038/s41587-020-0500-9","abstract":[{"lang":"eng","text":"Autoluminescent plants engineered to express a bacterial bioluminescence gene cluster in plastids have not been widely adopted because of low light output. We engineered tobacco plants with a fungal bioluminescence system that converts caffeic acid (present in all plants) into luciferin and report self-sustained luminescence that is visible to the naked eye. Our findings could underpin development of a suite of imaging tools for plants."}],"volume":38,"acknowledgement":"This study was designed, performed and funded by Planta LLC. We thank K. Wood for assisting in manuscript development. Planta acknowledges support from the Skolkovo Innovation Centre. We thank D. Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure. We thank S. Shakhov for providing\r\nphotography equipment. The Synthetic Biology Group is funded by the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0, K.S.S.). K.S.S. is supported by an Imperial College Research Fellowship. Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy\r\nof Sciences Сore Facility (CKP IBCH; supported by the Russian Ministry of Education and Science Grant RFMEFI62117X0018). The F.A.K. lab is supported by ERC grant agreement 771209—CharFL. This project received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie\r\nGrant Agreement 665385. K.S.S. acknowledges support by President’s Grant 075-15-2019-411. Design and assembly of some of the plasmids was supported by Russian Science Foundation grant 19-74-10102. Imaging experiments were partially supported by Russian Science Foundation grant 17-14-01169p. LC-MS/MS analyses of extracts were\r\nsupported by Russian Science Foundation grant 16-14-00052p. Design and assembly of plasmids was partially supported by grant 075-15-2019-1789 from the Ministry of Science and Higher Education of the Russian Federation allocated to the Center for Precision Genome Editing and Genetic Technologies for Biomedicine. The authors\r\nwould like to acknowledge the work of Genomics Core Facility of the Skolkovo Institute of Science and Technology, which performed the sequencing and bioinformatic analysis.","ddc":["570"],"has_accepted_license":"1","publication":"Nature Biotechnology","project":[{"_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209"}],"oa_version":"Submitted Version","month":"04","language":[{"iso":"eng"}],"type":"journal_article","date_published":"2020-04-27T00:00:00Z","publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"oa":1,"file":[{"relation":"main_file","access_level":"open_access","creator":"dernst","file_id":"8316","checksum":"1b30467500ec6277229a875b06e196d0","file_size":1180086,"embargo":"2021-03-01","date_created":"2020-08-28T08:57:07Z","content_type":"application/pdf","file_name":"2020_NatureBiotech_Mitiouchkina.pdf","date_updated":"2021-03-02T23:30:03Z"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41587-020-0578-0"}]}},{"language":[{"iso":"eng"}],"project":[{"name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209","call_identifier":"H2020","_id":"26580278-B435-11E9-9278-68D0E5697425"}],"oa_version":"Submitted Version","month":"12","publication":"Nature Biotechnology","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894943/"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"record":[{"id":"13059","relation":"research_data","status":"public"}]},"status":"public","publication_identifier":{"issn":["10870156"],"eissn":["15461696"]},"oa":1,"type":"journal_article","date_published":"2019-12-01T00:00:00Z","publisher":"Springer Nature","article_type":"original","ec_funded":1,"quality_controlled":"1","page":"1466-1470","department":[{"_id":"FyKo"}],"date_created":"2019-12-15T23:00:43Z","article_processing_charge":"No","publication_status":"published","intvolume":"        37","title":"Large multiple sequence alignments with a root-to-leaf regressive method","scopus_import":"1","_id":"7181","pmid":1,"issue":"12","author":[{"first_name":"Edgar","last_name":"Garriga","full_name":"Garriga, Edgar"},{"last_name":"Di Tommaso","first_name":"Paolo","full_name":"Di Tommaso, Paolo"},{"last_name":"Magis","first_name":"Cedrik","full_name":"Magis, Cedrik"},{"last_name":"Erb","first_name":"Ionas","full_name":"Erb, Ionas"},{"first_name":"Leila","last_name":"Mansouri","full_name":"Mansouri, Leila"},{"full_name":"Baltzis, Athanasios","first_name":"Athanasios","last_name":"Baltzis"},{"full_name":"Laayouni, Hafid","last_name":"Laayouni","first_name":"Hafid"},{"orcid":"0000-0001-8243-4694","full_name":"Kondrashov, Fyodor","first_name":"Fyodor","last_name":"Kondrashov","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Floden, Evan","last_name":"Floden","first_name":"Evan"},{"full_name":"Notredame, Cedric","last_name":"Notredame","first_name":"Cedric"}],"volume":37,"day":"01","doi":"10.1038/s41587-019-0333-6","abstract":[{"lang":"eng","text":"Multiple sequence alignments (MSAs) are used for structural1,2 and evolutionary predictions1,2, but the complexity of aligning large datasets requires the use of approximate solutions3, including the progressive algorithm4. Progressive MSA methods start by aligning the most similar sequences and subsequently incorporate the remaining sequences, from leaf-to-root, based on a guide-tree. Their accuracy declines substantially as the number of sequences is scaled up5. We introduce a regressive algorithm that enables MSA of up to 1.4 million sequences on a standard workstation and substantially improves accuracy on datasets larger than 10,000 sequences. Our regressive algorithm works the other way around to the progressive algorithm and begins by aligning the most dissimilar sequences. It uses an efficient divide-and-conquer strategy to run third-party alignment methods in linear time, regardless of their original complexity. Our approach will enable analyses of extremely large genomic datasets such as the recently announced Earth BioGenome Project, which comprises 1.5 million eukaryotic genomes6."}],"citation":{"apa":"Garriga, E., Di Tommaso, P., Magis, C., Erb, I., Mansouri, L., Baltzis, A., … Notredame, C. (2019). Large multiple sequence alignments with a root-to-leaf regressive method. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-019-0333-6\">https://doi.org/10.1038/s41587-019-0333-6</a>","ama":"Garriga E, Di Tommaso P, Magis C, et al. Large multiple sequence alignments with a root-to-leaf regressive method. <i>Nature Biotechnology</i>. 2019;37(12):1466-1470. doi:<a href=\"https://doi.org/10.1038/s41587-019-0333-6\">10.1038/s41587-019-0333-6</a>","ieee":"E. Garriga <i>et al.</i>, “Large multiple sequence alignments with a root-to-leaf regressive method,” <i>Nature Biotechnology</i>, vol. 37, no. 12. Springer Nature, pp. 1466–1470, 2019.","chicago":"Garriga, Edgar, Paolo Di Tommaso, Cedrik Magis, Ionas Erb, Leila Mansouri, Athanasios Baltzis, Hafid Laayouni, Fyodor Kondrashov, Evan Floden, and Cedric Notredame. “Large Multiple Sequence Alignments with a Root-to-Leaf Regressive Method.” <i>Nature Biotechnology</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41587-019-0333-6\">https://doi.org/10.1038/s41587-019-0333-6</a>.","mla":"Garriga, Edgar, et al. “Large Multiple Sequence Alignments with a Root-to-Leaf Regressive Method.” <i>Nature Biotechnology</i>, vol. 37, no. 12, Springer Nature, 2019, pp. 1466–70, doi:<a href=\"https://doi.org/10.1038/s41587-019-0333-6\">10.1038/s41587-019-0333-6</a>.","short":"E. Garriga, P. Di Tommaso, C. Magis, I. Erb, L. Mansouri, A. Baltzis, H. Laayouni, F. Kondrashov, E. Floden, C. Notredame, Nature Biotechnology 37 (2019) 1466–1470.","ista":"Garriga E, Di Tommaso P, Magis C, Erb I, Mansouri L, Baltzis A, Laayouni H, Kondrashov F, Floden E, Notredame C. 2019. Large multiple sequence alignments with a root-to-leaf regressive method. Nature Biotechnology. 37(12), 1466–1470."},"year":"2019","date_updated":"2023-09-06T14:32:52Z","external_id":{"isi":["000500748900021"],"pmid":["31792410"]},"isi":1}]