{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:06:42Z","timestamp":1772172402383,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1006459","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T00:00:00Z","timestamp":1538956800000}}],"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T00:00:00Z","timestamp":1537920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM114341"],"award-info":[{"award-number":["R01GM114341"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1006459","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T13:35:35Z","timestamp":1537968935000},"page":"e1006459","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["An information theoretic treatment of sequence-to-expression modeling"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-9122","authenticated-orcid":true,"given":"Farzaneh","family":"Khajouei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-7746","authenticated-orcid":true,"given":"Saurabh","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,9,26]]},"reference":[{"key":"ref1","article-title":"The Cell: A Molecular Approach","author":"GM Cooper","year":"2007","journal-title":"Sinauer Associates"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"R102","DOI":"10.1093\/hmg\/ddv259","article-title":"Non-coding genetic variants in human disease","author":"F Zhang","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"20140074","DOI":"10.1098\/rstb.2014.0074","article-title":"The role and interaction of imprinted genes in human fetal growth","volume":"370","author":"GE Moore","year":"2015","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/ng.1064","article-title":"Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development","volume":"44","author":"S Bonn","year":"2012","journal-title":"Nat Genet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1093\/nar\/gkv195","article-title":"Integrating motif, DNA accessibility and gene expression data to build regulatory maps in an organism","volume":"43","author":"C Blatti","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"E4914","DOI":"10.1073\/pnas.1704553114","article-title":"Modeling gene regulation from paired expression and chromatin accessibility data","volume":"114","author":"Z Duren","year":"2017","journal-title":"Proc Natl Acad Sci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pcbi.1004590","article-title":"Identification of High-Impact cis-Regulatory Mutations Using Transcription Factor Specific Random Forest Models","volume":"11","author":"D Svetlichnyy","year":"2015","journal-title":"PLoS Comput Biol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1371\/journal.pbio.1000456","article-title":"Quantitative analysis of the Drosophila segmentation regulatory network using pattern generating potentials","volume":"8","author":"M Kazemian","year":"2010","journal-title":"PLoS Biol"},{"key":"ref9","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2012-13-9-r49","article-title":"Analysis of variation at transcription factor binding sites in Drosophila and humans","volume":"13","author":"M Spivakov","year":"2012","journal-title":"Genome Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nmeth.3547","article-title":"Predicting effects of noncoding variants with deep learning\u2013based sequence model","volume":"12","author":"J Zhou","year":"2015","journal-title":"Nat Methods"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.3331","article-title":"A method to predict the impact of regulatory variants from DNA sequence","volume":"47","author":"D Lee","year":"2015","journal-title":"Nat Genet"},{"key":"ref12","first-page":"422","article-title":"Using graphical models and genomic expression data to statistically validate models of genetic regulatory networks","volume":"6","author":"AJ Hartemink","year":"2001","journal-title":"Pacific Symp Biocomput"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3109\/10409238.2011.556597","article-title":"Mathematical modeling of gene expression: a guide for the perplexed biologist","volume":"46","author":"A Ay","year":"2011","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nature06496","article-title":"Predicting expression patterns from regulatory sequence in Drosophila segmentation","volume":"451","author":"E Segal","year":"2008","journal-title":"Nature"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/ng1886","article-title":"Quantitative and predictive model of transcriptional control of the Drosophila melanogaster even skipped gene","volume":"38","author":"H Janssens","year":"2006","journal-title":"Nat Genet"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.08445","article-title":"Quantitative perturbation-based analysis of gene expression predicts enhancer activity in early Drosophila embryo","volume":"5","author":"R Sayal","year":"2016","journal-title":"Elife"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.cub.2006.05.044","article-title":"Computational Models for Neurogenic Gene Expression in the Drosophila Embryo","volume":"16","author":"RP Zinzen","year":"2006","journal-title":"Curr Biol"},{"key":"ref18","doi-asserted-by":"crossref","DOI":"10.1038\/msb.2012.48","article-title":"A model of spatially restricted transcription in opposing gradients of activators and repressors","volume":"8","author":"MA White","year":"2012","journal-title":"Mol Syst Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s12915-014-0102-4","article-title":"A framework for modelling gene regulation which accommodates non-equilibrium mechanisms","volume":"12","author":"T Ahsendorf","year":"2014","journal-title":"BMC Biol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature07521","article-title":"Analysis of combinatorial cis-regulation in synthetic and genomic promoters","volume":"457","author":"J Gertz","year":"2009","journal-title":"Nature"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.cels.2015.12.002","article-title":"A Systematic Ensemble Approach to Thermodynamic Modeling of Gene Expression from Sequence Data","volume":"1","author":"MAH Samee","year":"2015","journal-title":"Cell Syst"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e1000935","DOI":"10.1371\/journal.pcbi.1000935","article-title":"Thermodynamics-based models of transcriptional regulation by enhancers: The roles of synergistic activation, cooperative binding and short-range repression","volume":"6","author":"X He","year":"2010","journal-title":"PLoS Comput Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrg3207","article-title":"Transcription factors: from enhancer binding to developmental control","volume":"13","author":"F Spitz","year":"2012","journal-title":"Nat Rev Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1371\/journal.pcbi.0030189","article-title":"Universally sloppy parameter sensitivities in systems biology models","volume":"3","author":"RN Gutenkunst","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/nbt1330","article-title":"Ensemble modeling for analysis of cell signaling dynamics","volume":"25","author":"L Kuepfer","year":"2007","journal-title":"Nat Biotechnol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"21904","DOI":"10.1103\/PhysRevE.68.021904","article-title":"Statistical mechanical approaches to models with many poorly known parameters","volume":"68","author":"K Brown","year":"2003","journal-title":"Phys Rev E"},{"key":"ref27","volume":"112","author":"CFJ Wu","year":"2000"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1111\/j.1742-4658.2008.06843.x","article-title":"Systems biology: Experimental design","volume":"276","author":"C Kreutz","year":"2009","journal-title":"FEBS J"},{"key":"ref29","first-page":"363","article-title":"Robust design of biological experiments","author":"P Flaherty","year":"2006","journal-title":"Adv Neural Inf Process Syst"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ymeth.2013.05.012","article-title":"Global parameter estimation for thermodynamic models of transcriptional regulation","volume":"62","author":"Y Suleimenov","year":"2013","journal-title":"Methods"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1080\/01621459.1995.10476550","article-title":"Bayesian density estimation and inference using mixtures","volume":"90","author":"MD Escobar","year":"1995","journal-title":"J Am Stat Assoc"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1101\/gad.12.22.3591","article-title":"Dorsoventral patterning in the Drosophila central nervous system: The intermediate neuroblasts defective homeobox gene specifies intermediate column identity","volume":"12","author":"JB Weiss","year":"1998","journal-title":"Genes Dev"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.ydbio.2005.02.003","article-title":"Localized repressors delineate the neurogenic ectoderm in the early Drosophila embryo","volume":"280","author":"A Stathopoulos","year":"2005","journal-title":"Dev Biol"},{"key":"ref34","first-page":"362","article-title":"Convergence of Dorsal, Dpp, and Egfr Signaling Pathways Subdivides the Drosophila Neuroectoderm into Three Dorsal-Ventral Columns","volume":"372","author":"T Von Ohlen","year":"2000"},{"key":"ref35","article-title":"Temporal coordination of gene networks by Zelda in the early Drosophila embryo","volume":"7","author":"CY Nien","year":"2011","journal-title":"PLoS Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e29172","DOI":"10.1371\/journal.pone.0029172","article-title":"Lateral gene expression in Drosophila early embryos is supported by grainyhead-mediated activation and tiers of dorsally-localized repression","volume":"6","author":"M Garcia","year":"2011","journal-title":"PLoS One"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1101\/gad.12.22.3603","article-title":"Dorsoventral patterning in the Drosophila central nervous system: The vnd homeobox gene specifies ventral column identity","volume":"12","author":"JA McDonald","year":"1998","journal-title":"Genes Dev"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"10330","DOI":"10.1073\/pnas.1303635110","article-title":"Kinetics of gene derepression by ERK signaling","volume":"110","author":"B Lim","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref39","first-page":"171","article-title":"Specification of the Drosophila CNS midline cell lineage: Direct control of Single-Minded transcription by dorsal\/ventral patterning genes","volume":"7","author":"Y Kasai","year":"1998","journal-title":"Gene Expr"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0092-8674(88)90537-5","article-title":"Molecular genetics of the single-minded locus: A gene involved in the development of the Drosophila nervous system","volume":"52","author":"JB Thomas","year":"1988","journal-title":"Cell"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0092-8674(90)90288-P","article-title":"The single-minded Gene of Drosophila for the Expression of Genes Important Development of CNS Midline Cells Is Required for the","volume":"63","author":"JF Nambu","year":"1990","journal-title":"Cell"},{"key":"ref42","author":"ST Crews","year":"2012"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0092-8674(91)90292-7","article-title":"The Drosophila single-minded Gene Encodes a Helix-Loop-Helix Protein That Acts as a Master Regulator of CNS Midline Development","volume":"67","author":"JR Nambu","year":"1991","journal-title":"Cell"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1101\/gad.12.5.607","article-title":"Control of cell lineage-specific development and transcription by bHLH- PAS proteins","author":"ST Crews","year":"1998","journal-title":"Genes and Development"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1101\/gad.14.3.377","article-title":"Repression by Suppressor of Hairless and activation by Notch are required to define a single row of single-minded expressing cells in the Drosophila embryo","volume":"14","author":"V Morel","year":"2000","journal-title":"Genes Dev"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1242\/dev.129.7.1785","article-title":"The Snail repressor positions Notch signaling in the Drosophila embryo","volume":"129","author":"J Cowden","year":"2002","journal-title":"Development"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1242\/dev.121.1.219","article-title":"Neurogenic genes control gene expression at the transcriptional level in early neurogenesis and in mesectoderm specification","volume":"121","author":"MD Mart\u00edn-Bermudo","year":"1995","journal-title":"Development"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00427-003-0296-x","article-title":"Snail is required for Delta endocytosis and Notch-dependent activation of single-minded expression","volume":"213","author":"V Morel","year":"2003","journal-title":"Dev Genes Evol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1534\/genetics.116.186791","article-title":"Integration of orthogonal signaling by the notch and dpp pathways in Drosophila","volume":"203","author":"E Stroebele","year":"2016","journal-title":"Genetics"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0960-9822(01)00109-9","article-title":"Notch pathway: Making sense of suppressor of hairless","volume":"11","author":"S Bray","year":"2001","journal-title":"Curr Biol"},{"key":"ref51","first-page":"3","article-title":"Supplementary Materials for Mesodermal repression of single-minded in Drosophila embryo is mediated by a cluster of Snail-binding sites proximal to the early promoter","author":"KW Park"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"577","DOI":"10.5483\/BMBRep.2012.45.10.105","article-title":"Mesodermal repression of single-minded in drosophila embryo is mediated by a cluster of snail-binding sites proximal to the early promoter","volume":"45","author":"KW Park","year":"2012","journal-title":"BMB Rep"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00357-003-0015-3","article-title":"Enhanced Model-Based Clustering, Density Estimation, and Discriminant Analysis Software: MCLUST","volume":"20","author":"C Fraley","year":"2003","journal-title":"J Classif"},{"key":"ref54","author":"C Fraley","year":"2007"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/j.1538-7305.1948.tb01338.x","article-title":"A mathematical theory of communication","volume":"27","author":"C. Shannon","year":"1948","journal-title":"Bell Syst Tech J"},{"key":"ref56","article-title":"FlyFactorSurvey: A database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system","volume":"39","author":"LJ Zhu","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref57","first-page":"1699","article-title":"Predictive Entropy Search for Bayesian Optimization with Unknown Constraints","author":"JM Hern\u00e1ndez-Lobato","year":"2015","journal-title":"Proc Int Conf Mach Learn"},{"key":"ref58","first-page":"2960","article-title":"Practical Bayesian Optimization of Machine Learning Algorithms","volume":"25","author":"J Snoek","year":"2012","journal-title":"Adv Neural Inf Process Syst"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1214\/aoms\/1177728069","article-title":"On a Measure of the Information Provided by an Experiment","volume":"27","author":"D V. Lindley","year":"1956","journal-title":"Ann Math Stat"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1006459","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T00:00:00Z","timestamp":1538956800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006459","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T15:59:59Z","timestamp":1662134399000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006459"}},"subtitle":[],"editor":[{"given":"Alexandre V.","family":"Morozov","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,9,26]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1006459","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/316752","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,26]]}}}