{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:41:32Z","timestamp":1792791692754,"version":"4.5.0"},"reference-count":77,"publisher":"National Academy of Sciences","issue":"15","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM106189"],"award-info":[{"award-number":["R01GM106189"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM138533"],"award-info":[{"award-number":["R01GM138533"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009023","name":"MEXT | JST | Precursory Research for Embryonic Science and Technology","doi-asserted-by":"publisher","award":["JPMJPR21E4"],"award-info":[{"award-number":["JPMJPR21E4"]}],"id":[{"id":"10.13039\/501100009023","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swartz Foundation for Theoretical Neuroscience","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"https:\/\/ror.org\/04eqn7j88","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["F32MH118700"],"award-info":[{"award-number":["F32MH118700"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["K99DC019397"],"award-info":[{"award-number":["K99DC019397"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H05798"],"award-info":[{"award-number":["19H05798"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,4,11]]},"abstract":"<jats:p>Intensity-based time-lapse fluorescence resonance energy transfer (FRET) microscopy has been a major tool for investigating cellular processes, converting otherwise unobservable molecular interactions into fluorescence time series. However, inferring the molecular interaction dynamics from the observables remains a challenging inverse problem, particularly when measurement noise and photobleaching are nonnegligible\u2014a common situation in single-cell analysis. The conventional approach is to process the time-series data algebraically, but such methods inevitably accumulate the measurement noise and reduce the signal-to-noise ratio (SNR), limiting the scope of FRET microscopy. Here, we introduce an alternative probabilistic approach, B-FRET, generally applicable to standard 3-cube FRET-imaging data. Based on Bayesian filtering theory, B-FRET implements a statistically optimal way to infer molecular interactions and thus drastically improves the SNR. We validate B-FRET using simulated data and then apply it to real data, including the notoriously noisy in\u00a0vivo FRET time series from individual bacterial cells to reveal signaling dynamics otherwise hidden in the noise.<\/jats:p>","DOI":"10.1073\/pnas.2211807120","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T13:25:55Z","timestamp":1680614755000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Optimal inference of molecular interaction dynamics in FRET microscopy"],"prefix":"10.1073","volume":"120","author":[{"given":"Keita","family":"Kamino","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511"},{"name":"Quantitative Biology Institute, Yale University, New Haven, CT 06511"},{"name":"Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan"},{"name":"PRESTO, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 332-0012, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9978-6450","authenticated-orcid":false,"given":"Nirag","family":"Kadakia","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511"},{"name":"Quantitative Biology Institute, Yale University, New Haven, CT 06511"},{"name":"Swartz Foundation for Theoretical Neuroscience, Yale University, New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-7916","authenticated-orcid":false,"given":"Fotios","family":"Avgidis","sequence":"additional","affiliation":[{"name":"AMOLF Institute, Amsterdam 1098 XG, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6484-7652","authenticated-orcid":false,"given":"Zhe-Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Physics, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7263-1555","authenticated-orcid":false,"given":"Kazuhiro","family":"Aoki","sequence":"additional","affiliation":[{"name":"Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan"},{"name":"National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan"},{"name":"Department of Basic Biology, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 240-0193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0040-7380","authenticated-orcid":false,"given":"Thomas\u00a0S.","family":"Shimizu","sequence":"additional","affiliation":[{"name":"AMOLF Institute, Amsterdam 1098 XG, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6746-6564","authenticated-orcid":false,"given":"Thierry","family":"Emonet","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511"},{"name":"Quantitative Biology Institute, Yale University, New Haven, CT 06511"},{"name":"Department of Physics, Yale University, New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.005"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1201\/9781420011432"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1201\/9780429258893"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.11.025"},{"key":"e_1_3_5_5_2","volume-title":"Lakowicz: Principles of Fluorescence Spectroscopy","author":"Albrecht C.","year":"2008","unstructured":"C. Albrecht, R. Joseph, Lakowicz: Principles of Fluorescence Spectroscopy (Springer, 2008)."},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77976-7"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.103.022087"},{"key":"e_1_3_5_8_2","first-page":"1","article-title":"Calibration of fluorescence resonance energy transfer in microscopy using genetically engineered GFP derivatives on nickel chelating beads","volume":"3","author":"Youvan D. C.","year":"1997","unstructured":"D. C. Youvan , Calibration of fluorescence resonance energy transfer in microscopy using genetically engineered GFP derivatives on nickel chelating beads. Biotechnology 3, 1\u201318 (1997).","journal-title":"Biotechnology"},{"key":"e_1_3_5_9_2","first-page":"472","volume-title":"Methods in Enzymology","author":"Miyawaki A.","year":"2000","unstructured":"A. Miyawaki, R. Y. Tsien, \u201cMonitoring protein conformations and interactions by fluorescence resonance energy transfer between mutants of green fluorescent protein\u201d in Methods in Enzymology (Elsevier, 2000), vol. 327, pp. 472\u2013500."},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00438-X"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.106.088773"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-062215-010954"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136960"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3491"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/abc9d1"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coisb.2019.10.020"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0130-6"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coisb.2017.11.013"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2009.09.015"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1702181114"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1183415"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1610081113"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08012"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.27455"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41567-021-01380-3"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26796"},{"key":"e_1_3_5_27_2","doi-asserted-by":"crossref","unstructured":"K. Kamino J. M. Keegstra J. Long T. Emonet T. S. Shimizu Adaptive tuning of cell sensory diversity without changes in gene expression. Sci. Adv. 6 eabc1087 (2020). eabc1087","DOI":"10.1126\/sciadv.abc1087"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804598105"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1055835"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.09.015"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20220021"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20145584"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00654-5"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.074"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.61960"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.02.013"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.11.018"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/s16091488"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2171"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-01-0072"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth817"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.top071795"},{"key":"e_1_3_5_43_2","first-page":"774","volume-title":"Elements of Information Theory","author":"Cover T. M.","year":"2006","unstructured":"T. M. Cover, J. A. Thomas, Elements of Information Theory (Wiley, 2006), p. 774."},{"key":"e_1_3_5_44_2","first-page":"640","volume-title":"Information Theory, Inference, and Learning Algorithms","author":"MacKay D. J. C.","year":"2003","unstructured":"D. J. C. MacKay, Information Theory, Inference, and Learning Algorithms (Cambridge University Press, 2003), p. 640."},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/42264"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.09.031"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(03)75126-1"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.061853"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.111773"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164254"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.07.053"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/2046-1682-4-10"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1117\/1.2799171"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-072909-094736"},{"key":"e_1_3_5_55_2","unstructured":"S. Sarkka Bayesian Filtering and Smoothing (Cambridge University Press 2013) 10.1017\/CBO9781139344203."},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1201\/9781584889229"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20078"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3312006re2"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14840-w"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108760"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.011589998"},{"key":"e_1_3_5_62_2","first-page":"365","volume-title":"Methods in Enzymology","author":"Sourjik V.","year":"2007","unstructured":"V. Sourjik, A. Vaknin, T. S. Shimizu, H. C. Berg, \u201cIn vivo measurement by FRET of pathway activity in bacterial chemotaxis\u201d in Methods in Enzymology (Elsevier, 2007), vol. 423, pp. 365\u2013391."},{"key":"e_1_3_5_63_2","volume-title":"Pattern Recognition and Machine Learning","author":"Bishop C. M.","year":"2006","unstructured":"C. M. Bishop, Pattern Recognition and Machine Learning (Springer, 2006)."},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2015.03.003"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/16483"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.2011.01266.x"},{"key":"e_1_3_5_67_2","doi-asserted-by":"crossref","unstructured":"K. Kamino Y. Kondo Rescaling of spatio-temporal sensing in eukaryotic chemotaxis. PLOS One 18 e0164674 (2016). e0164674","DOI":"10.1371\/journal.pone.0164674"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102796"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03526"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(02)75365-4"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169337"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2009.09.031"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3435"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018586"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1007-767"},{"key":"e_1_3_5_76_2","unstructured":"K. Kamino N. Kadakia B-FRET. Github. https:\/\/github.com\/emonetlab. Deposited 5 July 2022."},{"key":"e_1_3_5_77_2","unstructured":"K. Kamino Data for: Optimal inference of molecular interaction dynamics in FRET microscopy. Dryad. https:\/\/datadryad.org\/stash\/dataset\/; doi:10.5061\/dryad.w3r2280w2. Deposited 23 March 2023."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2211807120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:55:58Z","timestamp":1695286558000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2211807120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,4]]},"references-count":77,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2023,4,11]]}},"alternative-id":["10.1073\/pnas.2211807120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2211807120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,4]]},"assertion":[{"value":"2022-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2211807120"}}