{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T23:54:45Z","timestamp":1775778885252,"version":"3.50.1"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["24784"],"award-info":[{"award-number":["24784"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite gene expression programs being notoriously complex, RNA abundance is usually assumed as a proxy for transcriptional activity. Recently developed approaches, able to disentangle transcriptional and post-transcriptional regulatory processes, have revealed a more complex scenario. It is now possible to work out how synthesis, processing and degradation kinetic rates collectively determine the abundance of each gene\u2019s RNA. It has become clear that the same transcriptional output can correspond to different combinations of the kinetic rates. This underscores the fact that markedly different modes of gene expression regulation exist, each with profound effects on a gene\u2019s ability to modulate its own expression. This review describes the development of the experimental and computational approaches, including RNA metabolic labeling and mathematical modeling, that have been disclosing the mechanisms underlying complex transcriptional programs. Current limitations and future perspectives in the field are also discussed.<\/jats:p>","DOI":"10.1093\/bib\/bbaa389","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T12:24:01Z","timestamp":1606825441000},"source":"Crossref","is-referenced-by-count":49,"title":["Dynamics of transcriptional and post-transcriptional regulation"],"prefix":"10.1093","volume":"22","author":[{"given":"Mattia","family":"Furlan","sequence":"first","affiliation":[{"name":"Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"de Pretis","sequence":"additional","affiliation":[{"name":"Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6672-9636","authenticated-orcid":false,"given":"Mattia","family":"Pelizzola","sequence":"additional","affiliation":[{"name":"Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"2021072117055203400_ref1","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.cell.2019.09.018","article-title":"Eukaryotic transcription turns 50","volume":"179","author":"Cramer","year":"2019","journal-title":"Cell"},{"key":"2021072117055203400_ref2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene expression omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"2021072117055203400_ref3","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1101\/gr.260984.120","article-title":"Genome-wide dynamics of RNA synthesis, processing, and degradation without RNA metabolic labeling","volume":"30","author":"Furlan","year":"2020","journal-title":"Genome Res"},{"key":"2021072117055203400_ref4","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.cell.2009.01.019","article-title":"The many pathways of RNA degradation","volume":"136","author":"Houseley","year":"2009","journal-title":"Cell"},{"key":"2021072117055203400_ref5","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/j.cell.2014.11.015","article-title":"High-resolution sequencing and modeling identifies distinct dynamic RNA regulatory strategies","volume":"159","author":"Rabani","year":"2014","journal-title":"Cell"},{"key":"2021072117055203400_ref6","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/msb.2011.62","article-title":"Coupled pre-mRNA and mRNA dynamics unveil operational strategies underlying transcriptional responses to stimuli","volume":"7","author":"Zeisel","year":"2011","journal-title":"Mol Syst Biol"},{"key":"2021072117055203400_ref7","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1093\/bioinformatics\/btv288","article-title":"INSPEcT: a computational tool to infer mRNA synthesis, processing and degradation dynamics from RNA- and 4sU-seq time course experiments","volume":"31","author":"Pretis","year":"2015","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2021072117055203400_ref8","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2001-2-10-research0041","article-title":"Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol","volume":"2","author":"Lam","year":"2001","journal-title":"Genome Biol"},{"key":"2021072117055203400_ref9","doi-asserted-by":"crossref","first-page":"5529","DOI":"10.1093\/nar\/gkf682","article-title":"Genome-wide analysis of mRNA decay in resting and activated primary human T lymphocytes","volume":"30","author":"Raghavan","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"2021072117055203400_ref10","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1101\/gr.1272403","article-title":"Decay rates of human mRNAs: correlation with functional characteristics and sequence attributes","volume":"13","author":"Yang","year":"2003","journal-title":"Genome Res"},{"key":"2021072117055203400_ref11","doi-asserted-by":"crossref","first-page":"781","DOI":"10.15252\/msb.20145794","article-title":"Genome-wide study of mRNA degradation and transcript elongation in Escherichia coli","volume":"11","author":"Chen","year":"2015","journal-title":"Mol Syst Biol"},{"key":"2021072117055203400_ref12","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1261\/rna.062877.117","article-title":"DRUID: a pipeline for transcriptome-wide measurements of mRNA stability","volume":"24","author":"Lugowski","year":"2018","journal-title":"RNA"},{"key":"2021072117055203400_ref13","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.cell.2015.02.029","article-title":"Codon optimality is a major determinant of mRNA stability","volume":"160","author":"Presnyak","year":"2015","journal-title":"Cell"},{"key":"2021072117055203400_ref14","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.3390\/ijms18122723","article-title":"Impact of methods on the measurement of mRNA turnover","volume":"18","author":"Wada","year":"2017","journal-title":"Int J Mol Sci"},{"key":"2021072117055203400_ref15","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nbt.1861","article-title":"Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells","volume":"29","author":"Rabani","year":"2011","journal-title":"Nat Biotechnol"},{"key":"2021072117055203400_ref16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000147","article-title":"A general definition and nomenclature for alternative splicing events","volume":"4","author":"Sammeth","year":"2008","journal-title":"PLoS Comput Biol"},{"key":"2021072117055203400_ref17","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1101\/gr.226035.117","article-title":"Integrative analysis of RNA polymerase II and transcriptional dynamics upon MYC activation","volume":"27","author":"Pretis","year":"2017","journal-title":"Genome Res"},{"key":"2021072117055203400_ref18","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nmeth.2483","article-title":"Comparative analysis of RNA sequencing methods for degraded or low-input samples","volume":"10","author":"Adiconis","year":"2013","journal-title":"Nat Methods"},{"key":"2021072117055203400_ref19","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nbt.3269","article-title":"Analysis of intronic and exonic reads in RNA-seq data characterizes transcriptional and post-transcriptional regulation","volume":"33","author":"Gaidatzis","year":"2015","journal-title":"Nat Biotechnol"},{"key":"2021072117055203400_ref20","first-page":"1","article-title":"Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer\u2019s disease","volume":"8","author":"Alkallas","year":"2018","journal-title":"Nat Commun"},{"key":"2021072117055203400_ref21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0089673","article-title":"SnapShot-Seq: a method for extracting genome-wide, in vivo mRNA dynamics from a single total RNA sample","volume":"9","author":"Gray","year":"2014","journal-title":"PLoS One"},{"key":"2021072117055203400_ref22","first-page":"6414","article-title":"Computational inference of mRNA stability from histone modification and transcriptome profiles","author":"Wang","year":"2012"},{"key":"2021072117055203400_ref23","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fgene.2020.00759","article-title":"INSPEcT-GUI reveals the impact of the kinetic rates of RNA synthesis, processing, and degradation, on premature and mature RNA species","volume":"11","author":"Pretis","year":"2020","journal-title":"Front Genet"},{"key":"2021072117055203400_ref24","doi-asserted-by":"crossref","DOI":"10.15252\/embr.201947987","article-title":"An early Myc-dependent transcriptional program orchestrates cell growth during B-cell activation","volume":"20","author":"Tesi","year":"2019","journal-title":"EMBO Rep"},{"key":"2021072117055203400_ref25","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1261\/rna.1136108","article-title":"High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay","volume":"14","author":"Dolken","year":"2008","journal-title":"RNA"},{"key":"2021072117055203400_ref26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41576-019-0159-6","article-title":"Nascent RNA analyses: tracking transcription and its regulation","volume":"20","author":"Wissink","year":"2019","journal-title":"Nat Rev Genet"},{"key":"2021072117055203400_ref27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3389\/fcell.2020.00097","article-title":"A protocol for Transcriptome-wide inference of RNA metabolic rates in mouse embryonic stem cells","volume":"8","author":"Biasini","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2021072117055203400_ref28","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1126\/science.1162228","article-title":"Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters","volume":"322","author":"Core","year":"2008","journal-title":"Science"},{"key":"2021072117055203400_ref29","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1126\/science.1229386","article-title":"Precise maps of RNA polymerase reveal how promoters direct initiation and pausing","volume":"339","author":"Kwak","year":"2013","journal-title":"Science"},{"key":"2021072117055203400_ref30","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1126\/science.aad9841","article-title":"TT-seq maps the human transient transcriptome","volume":"352","author":"Schwalb","year":"2016","journal-title":"Science"},{"key":"2021072117055203400_ref31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1007252","article-title":"On the optimal design of metabolic RNA labeling experiments","volume":"15","author":"Uvarovskii","year":"2019","journal-title":"PLoS Comput Biol"},{"key":"2021072117055203400_ref32","first-page":"884","article-title":"Measurement of genome-wide RNA synthesis and decay rates with dynamic transcriptome analysis (DTA)","author":"Schwalb","year":"2012"},{"key":"2021072117055203400_ref33","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1101\/gr.130161.111","article-title":"Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation","volume":"22","author":"Sun","year":"2012","journal-title":"Genome Res"},{"key":"2021072117055203400_ref34","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1093\/bioinformatics\/btx368","article-title":"Versatile computational analysis of RNA turnover from metabolic labeling experiments","volume":"33","author":"Uvarovskii","year":"2017","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2021072117055203400_ref35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nmeth.4608","article-title":"RNA dynamics revealed by metabolic RNA labeling and biochemical nucleoside conversions","volume":"15","author":"Baptista","year":"2018","journal-title":"Nat Methods"},{"key":"2021072117055203400_ref36","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/nmeth.4435","article-title":"Thiol-linked alkylation of RNA to assess expression dynamics","volume":"14","author":"Herzog","year":"2017","journal-title":"Nat Methods"},{"key":"2021072117055203400_ref37","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nmeth.4582","article-title":"TimeLapse-seq: adding a temporal dimension to RNA sequencing through nucleoside recoding","volume":"15","author":"Schofield","year":"2018","journal-title":"Nat Methods"},{"key":"2021072117055203400_ref38","doi-asserted-by":"crossref","first-page":"13479","DOI":"10.1002\/anie.201707465","article-title":"Osmium-mediated transformation of 4-Thiouridine to Cytidine as key to study RNA dynamics by sequencing","volume":"56","author":"Riml","year":"2017","journal-title":"Angew Chem Int Ed Engl"},{"key":"2021072117055203400_ref39","first-page":"631","article-title":"Thioguanosine conversion enables mRNA life-time evaluation by RNA sequencing via double metabolic labeling","volume":"20","author":"Gasser","year":"2020","journal-title":"Angew Chem Int Ed Engl"},{"key":"2021072117055203400_ref40","doi-asserted-by":"crossref","first-page":"i218","DOI":"10.1093\/bioinformatics\/bty256","article-title":"Dissecting newly transcribed and old RNA using GRAND-SLAM","volume":"34","author":"J\u00fcrges","year":"2018","journal-title":"Bioinformatics"},{"key":"2021072117055203400_ref41","doi-asserted-by":"crossref","DOI":"10.1186\/s12859-019-2849-7","article-title":"Quantification of experimentally induced nucleotide conversions in high-throughput sequencing datasets","volume":"20","author":"Neumann","year":"2019","journal-title":"BMC Bioinform"},{"key":"2021072117055203400_ref42","first-page":"120","article-title":"Metabolic labeling of RNA using multiple ribonucleoside analogs enables the simultaneous evaluation of RNA synthesis and degradation rates","volume":"264408","author":"Kawata","year":"2020","journal-title":"Genome Res"},{"key":"2021072117055203400_ref43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41586-018-0414-6","article-title":"RNA velocity of single cells","volume":"560","author":"La Manno","year":"2018","journal-title":"Nature"},{"key":"2021072117055203400_ref44","article-title":"Generalizing RNA velocity to transient cell states through dynamical modeling","volume":"14","author":"Bergen","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2021072117055203400_ref45","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1038\/s41467-019-11028-9","article-title":"NASC-seq monitors RNA synthesis in single cells","volume":"10","author":"Hendriks","year":"2019","journal-title":"Nat Commun"},{"key":"2021072117055203400_ref46","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/s41587-020-0480-9","article-title":"Sci-fate characterizes the dynamics of gene expression in single cells","volume":"38","author":"Cao","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2021072117055203400_ref47","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41586-019-1369-y","article-title":"scSLAM-seq reveals core features of transcription dynamics in single cells","volume":"571","author":"Erhard","year":"2019","journal-title":"Nature"},{"key":"2021072117055203400_ref48","first-page":"1","article-title":"Massively parallel and time-resolved RNA sequencing in single cells with scNT-seq","volume":"29","author":"Qiu","year":"2020","journal-title":"Nat Methods"},{"key":"2021072117055203400_ref49","first-page":"L25","article-title":"Mapping vector field of single cells","volume":"37","author":"Qiu","year":"2019","journal-title":"bioRxiv"},{"key":"2021072117055203400_ref50","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1126\/science.aax3072","article-title":"Sequencing metabolically labeled transcripts in single cells reveals mRNA turnover strategies","volume":"367","author":"Battich","year":"2020","journal-title":"Science"},{"key":"2021072117055203400_ref51","doi-asserted-by":"crossref","first-page":"12248","DOI":"10.1038\/ncomms12248","article-title":"A single-molecule view of transcription reveals convoys of RNA polymerases and multi-scale bursting","volume":"7","author":"Tantale","year":"2016","journal-title":"Nat Commun"},{"key":"2021072117055203400_ref52","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.45056","article-title":"Global donor and acceptor splicing site kinetics in human cells","volume":"8","author":"Wachutka","year":"2019","journal-title":"Elife"},{"key":"2021072117055203400_ref53","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/nrm.2017.63","article-title":"Splicing and transcription touch base: co-transcriptional spliceosome assembly and function","volume":"18","author":"Herzel","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2021072117055203400_ref54","doi-asserted-by":"crossref","first-page":"a032227","DOI":"10.1101\/cshperspect.a032227","article-title":"Nascent RNA and the coordination of splicing with transcription","volume":"11","author":"Neugebauer","year":"2019","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2021072117055203400_ref55","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrm.2015.15","article-title":"The regulation and functions of the nuclear RNA exosome complex","volume":"17","author":"Kilchert","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2021072117055203400_ref56","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1186\/s12864-017-4002-1","article-title":"Evaluation and comparison of computational tools for RNA-seq isoform quantification","volume":"18","author":"Zhang","year":"2017","journal-title":"BMC Genomics"},{"key":"2021072117055203400_ref57","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1038\/s41592-019-0617-2","article-title":"Nanopore native RNA sequencing of a human poly(a) transcriptome","volume":"16","author":"Workman","year":"2019","journal-title":"Nat Methods"},{"key":"2021072117055203400_ref58","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3389\/fgene.2020.00394","article-title":"Direct RNA sequencing for the study of synthesis, processing, and degradation of modified transcripts","volume":"11","author":"Furlan","year":"2020","journal-title":"Front Genet"},{"key":"2021072117055203400_ref59","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/cpmb.128","article-title":"Preparation of mammalian nascent RNA for long read sequencing","volume":"133","author":"Reimer","year":"2020","journal-title":"Curr Protoc Mol Biol"},{"key":"2021072117055203400_ref60","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1101\/gr.257857.119","article-title":"Native molecule sequencing by nano-ID reveals synthesis and stability of RNA isoforms","volume":"9","author":"Maier","year":"2020","journal-title":"Genome Res"},{"key":"2021072117055203400_ref61","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1038\/s41467-020-17800-6","article-title":"High throughput error corrected Nanopore single cell transcriptome sequencing","volume":"11","author":"Lebrigand","year":"2020","journal-title":"Nat Commun"},{"key":"2021072117055203400_ref62","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrm3953","article-title":"Getting up to speed with transcription elongation by RNA polymerase II","volume":"16","author":"Jonkers","year":"2015","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2021072117055203400_ref63","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.cell.2013.07.032","article-title":"Mechanistic interpretation of promoter-proximal peaks and RNAPII density maps","volume":"154","author":"Ehrensberger","year":"2013","journal-title":"Cell"},{"key":"2021072117055203400_ref64","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41586-020-2847-y","article-title":"The landscape of RNA pol II binding reveals a stepwise transition during ZGA","volume":"587","author":"Liu","year":"2020","journal-title":"Nature"},{"key":"2021072117055203400_ref65","doi-asserted-by":"crossref","DOI":"10.3390\/genes10010028","article-title":"m6A-dependent RNA dynamics in T cell differentiation","volume":"10","author":"Furlan","year":"2019","journal-title":"Genes"},{"key":"2021072117055203400_ref66","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.cell.2017.05.045","article-title":"Dynamic RNA modifications in gene expression regulation","volume":"169","author":"Roundtree","year":"2017","journal-title":"Cell"},{"key":"2021072117055203400_ref67","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/j.febslet.2008.03.004","article-title":"RNA-binding proteins and post-transcriptional gene regulation","volume":"582","author":"Glisovic","year":"2008","journal-title":"FEBS Lett"},{"key":"2021072117055203400_ref68","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/nsmb.3325","article-title":"Integrative classification of human coding and noncoding genes through RNA metabolism profiles","volume":"24","author":"Mukherjee","year":"2017","journal-title":"Nat Struct Mol Biol"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/4\/bbaa389\/39165037\/bbaa389.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/4\/bbaa389\/39165037\/bbaa389.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T18:06:40Z","timestamp":1669918000000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbaa389\/6043290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,22]]},"references-count":68,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,7,20]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbaa389","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,7]]},"published":{"date-parts":[[2020,12,22]]},"article-number":"bbaa389"}}