{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:44:52Z","timestamp":1790689492475,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011794","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000}}],"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013166","name":"Fondation G\u00e9n\u00e9rale de Sant\u00e9","doi-asserted-by":"publisher","award":["SPF201909009284"],"award-info":[{"award-number":["SPF201909009284"]}],"id":[{"id":"10.13039\/501100013166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["882673"],"award-info":[{"award-number":["882673"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PLAN CANCER","award":["20211007"],"award-info":[{"award-number":["20211007"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Phase separated domains (PSDs) are ubiquitous in cell biology, representing nanoregions of high molecular concentration. PSDs appear at diverse cellular domains, such as neuronal synapses but also in eukaryotic cell nucleus, limiting the access of transcription factors and thus preventing gene expression. We develop a generalized cross-linker polymer model, to study PSDs: we show that increasing the number of cross-linkers induces a polymer condensation, preventing access of diffusing molecules. To investigate how the PSDs restrict the motion of diffusing molecules, we compute the mean residence and first escaping times. Finally, we develop a method based on mean-square-displacement of single particle trajectories to reconstruct the properties of PSDs from the continuum range of anomalous exponents. We also show here that PSD generated by polymers do not induces a long-range attracting field (potential well), in contrast with nanodomains at neuronal synapses. To conclude, PSDs can result from condensed chromatin organization, where the number of cross-linkers controls molecular access.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011794","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T13:34:07Z","timestamp":1706103247000},"page":"e1011794","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Chromatin phase separated nanoregions explored by polymer cross-linker models and reconstructed from single particle trajectories"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9308-0729","authenticated-orcid":true,"given":"Andrea","family":"Papale","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-5014","authenticated-orcid":true,"given":"David","family":"Holcman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"issue":"2","key":"pcbi.1011794.ref001","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s00412-006-0052-x","article-title":"The contradictory definitions of heterochromatin: transcription and silencing","volume":"115","author":"K. L. Huisinga","year":"2006","journal-title":"Chromosoma"},{"issue":"5","key":"pcbi.1011794.ref002","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0168-9525(02)02648-3","article-title":"Unravelling heterochromatin: competition between positive and negative factors regulates accessibility","volume":"18","author":"N. Dillon","year":"2002","journal-title":"Trends in Genetics"},{"issue":"7648","key":"pcbi.1011794.ref003","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature21429","article-title":"3d structures of individual mammalian genomes studied by single-cell hi-c","volume":"544","author":"T. J. Stevens","year":"2017","journal-title":"Nature"},{"issue":"7","key":"pcbi.1011794.ref004","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.bpj.2017.02.023","article-title":"Three-dimensional super-resolution in eukaryotic cells using the double-helix point spread function","volume":"112","author":"A. R. Carr","year":"2017","journal-title":"Biophysical journal"},{"key":"pcbi.1011794.ref005","first-page":"2020","article-title":"Live-cell 3d single-molecule tracking reveals how nurd modulates enhancer dynamics","author":"S. Basu","year":"2021","journal-title":"Biorxiv"},{"issue":"33","key":"pcbi.1011794.ref006","doi-asserted-by":"crossref","first-page":"e2211855120","DOI":"10.1073\/pnas.2211855120","article-title":"Hp1-driven phase separation recapitulates the thermodynamics and kinetics of heterochromatin condensate formation","volume":"120","author":"M. M. Tortora","year":"2023","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"14","key":"pcbi.1011794.ref007","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1016\/j.bpj.2022.06.008","article-title":"Heterogeneous interactions and polymer entropy decide organization and dynamics of chromatin domains","volume":"121","author":"K. Kumari","year":"2022","journal-title":"Biophysical Journal"},{"issue":"1","key":"pcbi.1011794.ref008","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1039\/D2SM00612J","article-title":"Multivalent binding proteins can drive collapse and reswelling of chromatin in confinement","volume":"19","author":"S. Guha","year":"2023","journal-title":"Soft Matter"},{"issue":"5","key":"pcbi.1011794.ref009","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/ncb2472","article-title":"Increased chromosome mobility facilitates homology search during recombination","volume":"14","author":"J. Min\u00e9-Hattab","year":"2012","journal-title":"Nature cell biology"},{"issue":"2","key":"pcbi.1011794.ref010","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nsmb.3347","article-title":"Histone degradation in response to dna damage enhances chromatin dynamics and recombination rates","volume":"24","author":"M. H. Hauer","year":"2017","journal-title":"Nature structural & molecular biology"},{"issue":"1","key":"pcbi.1011794.ref011","doi-asserted-by":"crossref","first-page":"018102","DOI":"10.1103\/PhysRevLett.103.018102","article-title":"Transient anomalous diffusion of telomeres in the nucleus of mammalian cells","volume":"103","author":"I. Bronstein","year":"2009","journal-title":"Physical review letters"},{"issue":"9","key":"pcbi.1011794.ref012","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1016\/j.bpj.2012.09.040","article-title":"Universal algorithm for identification of fractional brownian motion. a case of telomere subdiffusion","volume":"103","author":"K. Burnecki","year":"2012","journal-title":"Biophysical journal"},{"issue":"1","key":"pcbi.1011794.ref013","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/19491034.2016.1139272","article-title":"Exploring chromatin organization mechanisms through its dynamic properties","volume":"7","author":"I. Bronshtein","year":"2016","journal-title":"Nucleus"},{"issue":"1","key":"pcbi.1011794.ref014","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-cellbio-100913-013325","article-title":"Liquid-liquid phase separation in biology","volume":"30","author":"A. A. Hyman","year":"2014","journal-title":"Annual Review of Cell and Developmental Biology"},{"issue":"5","key":"pcbi.1011794.ref015","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrm.2017.7","article-title":"Biomolecular condensates: organizers of cellular biochemistry","volume":"18","author":"S. F. Banani","year":"2017","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"pcbi.1011794.ref016","doi-asserted-by":"crossref","first-page":"043150","DOI":"10.1103\/PhysRevResearch.3.043150","article-title":"Stochastic dynamics of single molecules across phase boundaries","volume":"3","author":"S. Bo","year":"2021","journal-title":"Phys. Rev. Research"},{"key":"pcbi.1011794.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.conb.2018.12.001","article-title":"Phase separation as a mechanism for assembling dynamic postsynaptic density signalling complexes","volume":"57","author":"Z. Feng","year":"2019","journal-title":"Current opinion in neurobiology"},{"issue":"1","key":"pcbi.1011794.ref018","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.devcel.2020.06.012","article-title":"Liquid-liquid phase separation in neuronal development and synaptic signaling","volume":"55","author":"X. Wu","year":"2020","journal-title":"Developmental cell"},{"issue":"31","key":"pcbi.1011794.ref019","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1021\/acs.biochem.1c00376","article-title":"Liquid\u2013liquid phase separation in biology: Specific stoichiometric molecular interactions vs promiscuous interactions mediated by disordered sequences","volume":"60","author":"Z. Feng","year":"2021","journal-title":"Biochemistry"},{"issue":"5","key":"pcbi.1011794.ref020","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1523\/JNEUROSCI.1656-20.2020","article-title":"Liquid-liquid phase separation in physiology and pathophysiology of the nervous system","volume":"41","author":"Y. Hayashi","year":"2021","journal-title":"Journal of Neuroscience"},{"issue":"3","key":"pcbi.1011794.ref021","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.tins.2020.01.005","article-title":"Asymmetry between pre-and postsynaptic transient nanodomains shapes neuronal communication","volume":"43","author":"M. Heine","year":"2020","journal-title":"Trends in Neurosciences"},{"issue":"1","key":"pcbi.1011794.ref022","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cell.2017.02.007","article-title":"A phase separation model for transcriptional control","volume":"169","author":"D. Hnisz","year":"2017","journal-title":"Cell"},{"issue":"2","key":"pcbi.1011794.ref023","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.cell.2019.08.037","article-title":"Organization of chromatin by intrinsic and regulated phase separation","volume":"179","author":"B. A. Gibson","year":"2019","journal-title":"Cell"},{"issue":"1","key":"pcbi.1011794.ref024","first-page":"1","article-title":"Transcription organizes euchromatin via microphase separation","volume":"12","author":"L. Hilbert","year":"2021","journal-title":"Nature communications"},{"issue":"1","key":"pcbi.1011794.ref025","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1101\/gr.275827.121","article-title":"Spatial organization of chromosomes leads to heterogeneous chromatin motion and drives the liquid-or gel-like dynamical behavior of chromatin","volume":"32","author":"H. Salari","year":"2022","journal-title":"Genome Research"},{"issue":"7662","key":"pcbi.1011794.ref026","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nature22989","article-title":"Phase separation drives heterochromatin domain formation","volume":"547","author":"A. R. Strom","year":"2017","journal-title":"Nature"},{"key":"pcbi.1011794.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.physrep.2017.02.002","article-title":"Polymer physics of nuclear organization and function","volume":"678","author":"A. Amitai","year":"2017","journal-title":"Physics Reports"},{"issue":"40","key":"pcbi.1011794.ref028","doi-asserted-by":"crossref","first-page":"16173","DOI":"10.1073\/pnas.1204799109","article-title":"Complexity of chromatin folding is captured by the strings and binders switch model","volume":"109","author":"M. Barbieri","year":"2012","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"1","key":"pcbi.1011794.ref029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep29775","article-title":"Polymer physics of chromosome large-scale 3d organisation","volume":"6","author":"A. M. Chiariello","year":"2016","journal-title":"Scientific reports"},{"issue":"1","key":"pcbi.1011794.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-25875-y","article-title":"Complex small-world regulatory networks emerge from the 3d organisation of the human genome","volume":"12","author":"C. Brackley","year":"2021","journal-title":"Nature communications"},{"issue":"15","key":"pcbi.1011794.ref031","doi-asserted-by":"crossref","first-page":"9553","DOI":"10.1093\/nar\/gku698","article-title":"Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains","volume":"42","author":"D. Jost","year":"2014","journal-title":"Nucleic acids research"},{"issue":"4","key":"pcbi.1011794.ref032","doi-asserted-by":"crossref","first-page":"041047","DOI":"10.1103\/PhysRevX.6.041047","article-title":"Polymer model with epigenetic recoloring reveals a pathway for the de novo establishment and 3d organization of chromatin domains","volume":"6","author":"D. Michieletto","year":"2016","journal-title":"Physical Review X"},{"issue":"14","key":"pcbi.1011794.ref033","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1016\/j.bpj.2022.06.008","article-title":"Heterogeneous interactions and polymer entropy decide organization and dynamics of chromatin domains","volume":"121","author":"K. Kumari","year":"2022","journal-title":"Biophysical Journal"},{"issue":"1","key":"pcbi.1011794.ref034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-10842-9","article-title":"Two loci single particle trajectories analysis: constructing a first passage time statistics of local chromatin exploration","volume":"7","author":"O. Shukron","year":"2017","journal-title":"Scientific reports"},{"key":"pcbi.1011794.ref035","article-title":"A complex ctcf binding code defines tad boundary structure and function","author":"L.-H. Chang","year":"2021","journal-title":"bioRxiv"},{"key":"pcbi.1011794.ref036","doi-asserted-by":"crossref","first-page":"258102","DOI":"10.1103\/PhysRevLett.126.258102","article-title":"Mechanical frustration of phase separation in the cell nucleus by chromatin","volume":"126","author":"Y. Zhang","year":"2021","journal-title":"Phys. Rev. Lett"},{"issue":"1","key":"pcbi.1011794.ref037","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1039\/D2SM00612J","article-title":"Multivalent binding proteins can drive collapse and reswelling of chromatin in confinement","volume":"19","author":"S. Guha","year":"2023","journal-title":"Soft Matter"},{"issue":"2","key":"pcbi.1011794.ref038","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.cell.2014.05.036","article-title":"3d trajectories adopted by coding and regulatory dna elements: First-passage times for genomic interactions","volume":"158","author":"J. S. Lucas","year":"2014","journal-title":"Cell"},{"key":"pcbi.1011794.ref039","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1146\/annurev-biophys-062215-010925","article-title":"First-passage processes in the genome","volume":"45","author":"Y. Zhang","year":"2016","journal-title":"Annual review of biophysics"},{"issue":"1","key":"pcbi.1011794.ref040","doi-asserted-by":"crossref","first-page":"012503","DOI":"10.1103\/PhysRevE.96.012503","article-title":"Statistics of randomly cross-linked polymer models to interpret chromatin conformation capture data","volume":"96","author":"O. Shukron","year":"2017","journal-title":"Physical Review E"},{"issue":"1","key":"pcbi.1011794.ref041","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-10628-9","article-title":"Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions","volume":"10","author":"N. Khanna","year":"2019","journal-title":"Nature communications"},{"key":"pcbi.1011794.ref042","doi-asserted-by":"crossref","first-page":"3628","DOI":"10.1103\/PhysRevA.33.3628","article-title":"Molecular dynamics simulation for polymers in the presence of a heat bath","volume":"33","author":"G. S. Grest","year":"1986","journal-title":"Phys. Rev. A"},{"key":"pcbi.1011794.ref043","doi-asserted-by":"crossref","first-page":"e1000153","DOI":"10.1371\/journal.pcbi.1000153","article-title":"Structure and dynamics of interphase chromosomes","volume":"4","author":"A. Rosa","year":"2008","journal-title":"PLOS Comput Biol"},{"issue":"22","key":"pcbi.1011794.ref044","doi-asserted-by":"crossref","first-page":"11202","DOI":"10.1093\/nar\/gks925","article-title":"Self-organization of domain structures by dna-loop-extruding enzymes","volume":"40","author":"E. Alipour","year":"2012","journal-title":"Nucleic acids research"},{"issue":"9","key":"pcbi.1011794.ref045","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1016\/j.celrep.2016.04.085","article-title":"Formation of chromosomal domains by loop extrusion","volume":"15","author":"G. Fudenberg","year":"2016","journal-title":"Cell reports"},{"key":"pcbi.1011794.ref046","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1016\/j.csbj.2022.05.044","article-title":"Ctcf: A misguided jack-of-all-trades in cancer cells","volume":"20","author":"J. Segueni","year":"2022","journal-title":"Computational and Structural Biotechnology Journal"},{"key":"pcbi.1011794.ref047","volume-title":"Scaling concepts in polymer physics","author":"P.-G. De Gennes","year":"1979"},{"issue":"1","key":"pcbi.1011794.ref048","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/jcph.1995.1039","article-title":"Fast parallel algorithms for short-range molecular dynamics","volume":"117","author":"S. Plimpton","year":"1995","journal-title":"Journal of computational physics"},{"issue":"18","key":"pcbi.1011794.ref049","doi-asserted-by":"crossref","first-page":"7726","DOI":"10.1021\/la052651k","article-title":"Fast method for computing pore size distributions of model materials","volume":"22","author":"S. Bhattacharya","year":"2006","journal-title":"Langmuir"},{"issue":"7","key":"pcbi.1011794.ref050","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1021\/acs.macromol.9b02166","article-title":"Determining the mesh size of polymer solutions via the pore size distribution","volume":"53","author":"V. Sorichetti","year":"2020","journal-title":"Macromolecules"},{"issue":"42","key":"pcbi.1011794.ref051","doi-asserted-by":"crossref","first-page":"17052","DOI":"10.1073\/pnas.1204589109","article-title":"Heterogeneity of ampa receptor trafficking and molecular interactions revealed by superresolution analysis of live cell imaging","volume":"109","author":"N. Hoze","year":"2012","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"12","key":"pcbi.1011794.ref052","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1016\/j.bpj.2014.10.018","article-title":"Residence times of receptors in dendritic spines analyzed by stochastic simulations in empirical domains","volume":"107","author":"N. Hoze","year":"2014","journal-title":"Biophysical journal"},{"key":"pcbi.1011794.ref053","volume-title":"Theory and applications of stochastic processes: an analytical approach, vol. 170 of Applied Mathematical Sciences","author":"Z. Schuss","year":"2009"},{"issue":"5","key":"pcbi.1011794.ref054","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1103\/PhysRevLett.78.863","article-title":"Description of a turbulent cascade by a fokker-planck equation","volume":"78","author":"R. Friedrich","year":"1997","journal-title":"Physical Review Letters"},{"key":"pcbi.1011794.ref055","doi-asserted-by":"crossref","unstructured":"Hoz\u00e9 N. and Holcman D., \u201cStatistical methods for large ensembles of super-resolution stochastic single particle trajectories in cell biology,\u201d 2017.","DOI":"10.1101\/227090"},{"issue":"3","key":"pcbi.1011794.ref056","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1137\/100782620","article-title":"An asymptotic analysis of the mean first passage time for narrow escape problems: Part ii: The sphere","volume":"8","author":"A. F. Cheviakov","year":"2010","journal-title":"Multiscale Modeling & Simulation"},{"issue":"9","key":"pcbi.1011794.ref057","doi-asserted-by":"crossref","first-page":"094909","DOI":"10.1063\/1.3081633","article-title":"Narrow escape time to a structured target located on the boundary of a microdomain","volume":"130","author":"J. Reingruber","year":"2009","journal-title":"The Journal of Chemical Physics"},{"issue":"6592","key":"pcbi.1011794.ref058","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1126\/science.abn6583","article-title":"Dynamics of ctcf-and cohesin-mediated chromatin looping revealed by live-cell imaging","volume":"376","author":"M. Gabriele","year":"2022","journal-title":"Science"},{"issue":"6","key":"pcbi.1011794.ref059","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/j.celrep.2012.11.008","article-title":"Local nucleosome dynamics facilitate chromatin accessibility in living mammalian cells","volume":"2","author":"S. Hihara","year":"2012","journal-title":"Cell reports"},{"key":"pcbi.1011794.ref060","doi-asserted-by":"crossref","first-page":"e25776","DOI":"10.7554\/eLife.25776","article-title":"Ctcf and cohesin regulate chromatin loop stability with distinct dynamics","volume":"6","author":"A. S. Hansen","year":"2017","journal-title":"elife"},{"issue":"2","key":"pcbi.1011794.ref061","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.molcel.2020.02.005","article-title":"Mouse heterochromatin adopts digital compaction states without showing hallmarks of hp1-driven liquid-liquid phase separation","volume":"78","author":"F. Erdel","year":"2020","journal-title":"Molecular cell"},{"issue":"11","key":"pcbi.1011794.ref062","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1016\/j.bpj.2010.01.054","article-title":"Looping probabilities in model interphase chromosomes","volume":"98","author":"A. Rosa","year":"2010","journal-title":"Biophysical journal"},{"issue":"11","key":"pcbi.1011794.ref063","doi-asserted-by":"crossref","first-page":"118302","DOI":"10.1103\/PhysRevLett.112.118302","article-title":"Ring polymers in the melt state: the physics of crumpling","volume":"112","author":"A. Rosa","year":"2014","journal-title":"Physical review letters"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011794","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011794","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T13:38:50Z","timestamp":1707140330000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011794"}},"subtitle":[],"editor":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,24]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011794","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,24]]}}}