{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T03:11:03Z","timestamp":1782097863185,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1006484","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000}}],"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM115836"],"award-info":[{"award-number":["R01GM115836"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM127087"],"award-info":[{"award-number":["R35GM127087"]}],"id":[{"id":"10.13039\/100000057","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.1006484","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T13:46:41Z","timestamp":1538660801000},"page":"e1006484","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":92,"title":["Prediction of gene regulatory enhancers across species reveals evolutionarily conserved sequence properties"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-1852","authenticated-orcid":true,"given":"Ling","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Fish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-1795","authenticated-orcid":true,"given":"John A.","family":"Capra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,10,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nrg3682","article-title":"Transcriptional enhancers: from properties to genome-wide predictions","volume":"15","author":"D Shlyueva","year":"2014","journal-title":"Nat Rev Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature14248","article-title":"Integrative analysis of 111 reference human epigenomes","volume":"518","author":"RE Consortium","year":"2015","journal-title":"Nature"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic Localization of Common Disease-Associated Variation in Regulatory DNA","volume":"337","author":"MT Maurano","year":"2012","journal-title":"Science"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13073-014-0085-3","article-title":"Enhancer variants: evaluating functions in common disease","volume":"6","author":"O Corradin","year":"2014","journal-title":"Genome Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/path.4647","article-title":"The complexity of epigenetic diseases","author":"AJ Brazel","year":"2016","journal-title":"Journal of Pathology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1101\/gr.119016.110","article-title":"Genome-wide identification of conserved regulatory function in diverged sequences","volume":"21","author":"L Taher","year":"2011","journal-title":"Genome Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/molbev\/mss022","article-title":"Evolutionary conservation of histone modifications in mammals","volume":"29","author":"YH Woo","year":"2012","journal-title":"Mol Biol Evol"},{"key":"ref8","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2013.05.056","article-title":"The evolution of lineage-specific regulatory activities in the human embryonic limb","volume":"154","author":"J Cotney","year":"2013","journal-title":"Cell"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"20120366","DOI":"10.1098\/rstb.2012.0366","article-title":"Effects of gene regulatory reprogramming on gene expression in human and mouse developing hearts","volume":"368","author":"C-H Hsu","year":"2013","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrg3481","article-title":"Evolution of transcription factor binding in metazoans\u2014mechanisms and functional implications","volume":"15","author":"D Villar","year":"2014","journal-title":"Nat Rev Genet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1126\/science.1260943","article-title":"Evolutionary changes in promoter and enhancer activity during human corticogenesis","volume":"347","author":"SK Reilly","year":"2015","journal-title":"Science"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cell.2015.01.006","article-title":"Enhancer evolution across 20 mammalian species","volume":"160","author":"D Villar","year":"2015","journal-title":"Cell"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nature13972","article-title":"Conservation of trans-acting circuitry during mammalian regulatory evolution","volume":"515","author":"AB Stergachis","year":"2014","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/jbiol130","article-title":"Conservation of core gene expression in vertebrate tissues","volume":"8","author":"ET Chan","year":"2009","journal-title":"J Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature10532","article-title":"The evolution of gene expression levels in mammalian organs","volume":"478","author":"D Brawand","year":"2011","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1126\/science.1228186","article-title":"Evolutionary dynamics of gene and isoform regulation in Mammalian tissues","volume":"338","author":"J Merkin","year":"2012","journal-title":"Science"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/molbev\/msl211","article-title":"One billion years of bZIP transcription factor evolution: Conservation and change in dimerization and DNA-binding site specificity","volume":"24","author":"GD Amoutzias","year":"2007","journal-title":"Mol Biol Evol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.04837","article-title":"Conservation of transcription factor binding specificities across 600 million years of bilateria evolution","volume":"4","author":"KR Nitta","year":"2015","journal-title":"Elife"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/emboj.2010.106","article-title":"Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo","volume":"29","author":"G-H Wei","year":"2010","journal-title":"EMBO J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nature13985","article-title":"Principles of regulatory information conservation between mouse and human","volume":"515","author":"Y Cheng","year":"2014","journal-title":"Nature"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1126\/science.1160930","article-title":"Species-specific transcription in mice carrying human chromosome 21","volume":"322","author":"MD Wilson","year":"2008","journal-title":"Science"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1093\/molbev\/msq128","article-title":"The importance of Being Cis: Evolution of Orthologous Fish and Mammalian enhancer activity","volume":"27","author":"DI Ritter","year":"2010","journal-title":"Mol Biol Evol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1126\/science.1186176","article-title":"Five-Vertebrate ChIP-seq Reveals the Evolutionary Dynamics of Transcription Factor Binding","volume":"328","author":"D Schmidt","year":"2010","journal-title":"Science"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1093\/molbev\/msv118","article-title":"Human enhancers are fragile and prone to deactivating mutations","volume":"32","author":"S Li","year":"2015","journal-title":"Mol Biol Evol"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Prescott SL, Srinivasan R, Marchetto MC, Gage FH, Swigut T, Selleri L, et al. Enhancer Divergence and cis -Regulatory Evolution in the Human and Chimp Neural Crest Article Enhancer Divergence and cis -Regulatory Evolution in the Human and Chimp Neural Crest. 2015; 68\u201383. <comment>doi: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.1016\/j.cell.2015.08.036\" xlink:type=\"simple\">10.1016\/j.cell.2015.08.036<\/ext-link><\/comment>","DOI":"10.1016\/j.cell.2015.08.036"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0092-8674(81)90413-X","article-title":"Expression of a \u03b2-globin gene is enhanced by remote SV40 DNA sequences","volume":"27","author":"J Banerji","year":"1981","journal-title":"Cell"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.cell.2013.11.033","article-title":"Rapid and pervasive changes in genome-wide enhancer usage during mammalian development","volume":"155","author":"AS Nord","year":"2013","journal-title":"Cell"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"21931","DOI":"10.1073\/pnas.1016071107","article-title":"Histone H3K27ac separates active from poised enhancers and predicts developmental state","volume":"107","author":"MP Creyghton","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1101\/gr.129817.111","article-title":"Chromatin state signatures associated with tissue-specific gene expression and enhancer activity in the embryonic limb","volume":"22","author":"J Cotney","year":"2012","journal-title":"Genome Res"},{"key":"ref30","first-page":"e1003677","article-title":"Integrating diverse datasets improves developmental enhancer prediction. PLoS Comput Biol","volume":"10","author":"GD Erwin","year":"2014"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1101\/gr.121905.111","article-title":"Discriminative prediction of mammalian enhancers from DNA sequence","volume":"21","author":"D Lee","year":"2011","journal-title":"Genome Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1101\/gr.139717.112","article-title":"Systematic elucidation and in vivo validation of sequences enriched in hindbrain transcriptional control","volume":"22","author":"GM Burzynski","year":"2012","journal-title":"Genome Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/bioinformatics\/btr704","article-title":"Clare: Cracking the LAnguage of regulatory elements","volume":"28","author":"L Taher","year":"2012","journal-title":"Bioinformatics"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"e1003711","DOI":"10.1371\/journal.pcbi.1003711","article-title":"Enhanced regulatory sequence prediction using gapped k-mer features","volume":"10","author":"M Ghandi","year":"2014","journal-title":"PLoS Comput Biol"},{"key":"ref35","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":"ref36","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nmeth.3547","article-title":"Predicting effects of noncoding variants with deep learning-based sequence model","volume":"12","author":"J Zhou","year":"2015","journal-title":"Nat Methods"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1093\/nar\/gkw226","article-title":"DanQ: a hybrid convolutional and recurrent deep neural network for quantifying the function of DNA sequences","volume":"44","author":"D Quang","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Min X, Chen N, Chen T, Jiang R. DeepEnhancer: Predicting enhancers by convolutional neural networks. Proceedings\u20142016 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2016. 2017. pp. 637\u2013644. <comment>doi: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.1109\/BIBM.2016.7822593\" xlink:type=\"simple\">10.1109\/BIBM.2016.7822593<\/ext-link><\/comment>","DOI":"10.1109\/BIBM.2016.7822593"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1093\/bioinformatics\/btx105","article-title":"BiRen: Predicting enhancers with a deep-learning-based model using the DNA sequence alone","volume":"33","author":"B Yang","year":"2017","journal-title":"Bioinformatics"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1093\/bioinformatics\/btq358","article-title":"An alignment-free method to identify candidate orthologous enhancers in multiple Drosophila genomes","volume":"26","author":"M Arunachalam","year":"2010","journal-title":"Bioinformatics"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1093\/gbe\/evu184","article-title":"Evidence for deep regulatory similarities in early developmental programs across highly diverged insects","volume":"6","author":"M Kazemian","year":"2014","journal-title":"Genome Biol Evol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.cell.2013.07.007","article-title":"Cooperativity and rapid evolution of cobound transcription factors in closely related mammals","volume":"154","author":"K Stefflova","year":"2013","journal-title":"Cell"},{"key":"ref43","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.11615","article-title":"Evidence for a common evolutionary rate in metazoan transcriptional networks","volume":"4","author":"AR Carvunis","year":"2015","journal-title":"Elife"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Quang D, Xie X. FactorNet: a deep learning framework for predicting cell type specific transcription factor binding from nucleotide-resolution sequential data. 2017; 1\u201328.","DOI":"10.1101\/151274"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/nbt.3300","article-title":"Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning","volume":"33","author":"B Alipanahi","year":"2015","journal-title":"Nat Biotechnol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1101\/gr.200535.115","article-title":"Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks","volume":"26","author":"DR Kelley","year":"2016","journal-title":"Genome Res"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1126\/science.1260943","article-title":"Evolutionary changes in promoter and enhancer activity during human corticogenesis","volume":"347","author":"SK Reilly","year":"2015","journal-title":"Science"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1101\/gr.139360.112","article-title":"Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes","volume":"22","author":"DU Gorkin","year":"2012","journal-title":"Genome Res"},{"key":"ref49","first-page":"1","article-title":"KeBABS: an R package for kernel-based analysis of biological sequences","author":"J Palme","year":"2015","journal-title":"Bioinformatics"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1093\/bib\/bbv101","article-title":"Progress and challenges in bioinformatics approaches for enhancer identification","volume":"17","author":"D Kleftogiannis","year":"2016","journal-title":"Brief Bioinform."},{"key":"ref51","first-page":"1","article-title":"Genome-wide Enhancer Maps Differ Significantly in Genomic Distribution, Evolution, and Function","author":"ML Benton","year":"2017","journal-title":"bioRxiv"},{"key":"ref52","article-title":"Evolution of Alu Elements toward Enhancers","author":"M Su","year":"2014","journal-title":"Cell Reports"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/ng.2553","article-title":"Endogenous retroviruses function as species-specific enhancer elements in the placenta","volume":"45","author":"EB Chuong","year":"2013","journal-title":"Nat Genet"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev-genet-110711-155621","article-title":"Transposable elements: an abundant and natural source of regulatory sequences for host genes","volume":"46","author":"R Rebollo","year":"2012","journal-title":"Annu Rev Genet"},{"key":"ref55","article-title":"Transposable Element Exaptation into Regulatory Regions is Rare, Influenced by Evolutionary Age, and Subject to Pleiotropic Constraints","author":"CN Simonti","year":"2017","journal-title":"Mol Biol Evol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrg2538","article-title":"A census of human transcription factors: function, expression and evolution","volume":"10","author":"JM Vaquerizas","year":"2009","journal-title":"Nat Rev Genet"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"D142","DOI":"10.1093\/nar\/gkt997","article-title":"JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles","volume":"42","author":"A Mathelier","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"BE Bernstein","year":"2012","journal-title":"Nature"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: tool for the unification of biology","volume":"25","year":"2000","journal-title":"Nat Genet"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"D1049","DOI":"10.1093\/nar\/gku1179","article-title":"Gene Ontology Consortium: going forward","volume":"43","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00441-011-1246-y","article-title":"TGF-\u03b2 in progression of liver disease","volume":"347","author":"S Dooley","year":"2012","journal-title":"Cell Tissue Res"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1083\/jcb.145.5.1049","article-title":"Functions of c-Jun in liver and heart development","volume":"145","author":"R Eferl","year":"1999","journal-title":"J Cell Biol"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1128\/MCB.06543-11","article-title":"Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins","volume":"32","author":"H Yamazaki","year":"2012","journal-title":"Mol Cell Biol"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"M Uhlen","year":"2015","journal-title":"Science"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nature13668","article-title":"Comparative analysis of regulatory information and circuits across distant species","volume":"512","author":"AP Boyle","year":"2014","journal-title":"Nature"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature12787","article-title":"An atlas of active enhancers across human cell types and tissues","volume":"507","author":"R Andersson","year":"2014","journal-title":"Nature"},{"key":"ref67","doi-asserted-by":"crossref","DOI":"10.1186\/s13072-015-0009-5","article-title":"Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility","volume":"8","author":"N Dogan","year":"2015","journal-title":"Epigenetics and Chromatin"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nature13668","article-title":"Comparative analysis of regulatory information and circuits across distant species","volume":"512","author":"AP Boyle","year":"2014","journal-title":"Nature"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrg3481","article-title":"Evolution of transcription factor binding in metazoans\u2014mechanisms and functional implications","volume":"15","author":"D Villar","year":"2014","journal-title":"Nat Rev Genet"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12864-015-1264-3","article-title":"Extrapolating histone marks across developmental stages, tissues, and species: an enhancer prediction case study","volume":"16","author":"JA Capra","year":"2015","journal-title":"BMC Genomics"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.tibs.2014.07.002","article-title":"Absence of a simple code: How transcription factors read the genome","author":"M Slattery","year":"2014","journal-title":"Trends in Biochemical Sciences"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/nar\/gkt1196","article-title":"Ensembl 2014","volume":"42","author":"P Flicek","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cell.2015.01.006","article-title":"Enhancer Evolution across 20 Mammalian Species","volume":"160","author":"D Villar","year":"2015","journal-title":"Cell"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cell.2015.01.006","article-title":"Enhancer Evolution across 20 Mammalian Species","volume":"160","author":"D Villar","year":"2015","journal-title":"Cell"},{"key":"ref75","unstructured":"Smit A, Hubley R, Green P. RepeatMasker Open-4.0. 2013\u20132015. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.repeatmasker.org\" xlink:type=\"simple\">http:\/\/www.repeatmasker.org<\/ext-link>. 2013."},{"key":"ref76","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1126\/science.1260943","article-title":"Evolutionary genomics. Evolutionary changes in promoter and enhancer activity during human corticogenesis","volume":"347","author":"SK Reilly","year":"2015","journal-title":"Science"},{"key":"ref77","first-page":"88","article-title":"VISTA Enhancer Browser\u2014a database of tissue-specific human enhancers","volume":"35","author":"A Visel","year":"2007"},{"key":"ref78","first-page":"564","article-title":"The spectrum kernel: a string kernel for SVM protein classification","volume":"575","author":"C Leslie","year":"2002","journal-title":"Pac Symp Biocomput"},{"key":"ref79","first-page":"M110.004994","article-title":"Complex Networks Govern Coiled-Coil Oligomerization\u2013Predicting and Profiling by Means of a Machine Learning Approach. Mol Cell Proteomics","volume":"10","author":"CC Mahrenholz","year":"2011","journal-title":"The American Society for Biochemistry and Molecular Biology"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"R24","DOI":"10.1186\/gb-2007-8-2-r24","article-title":"Quantifying similarity between motifs","volume":"8","author":"S Gupta","year":"2007","journal-title":"Genome Biol"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1093\/bioinformatics\/btx364","article-title":"UpSetR: An R package for the visualization of intersecting sets and their properties","volume":"33","author":"JR Conway","year":"2017","journal-title":"Bioinformatics"},{"key":"ref82","first-page":"1","article-title":"Complexity and conservation of regulatory landscapes underlie evolutionary resilience of mammalian gene expression","author":"C Berthelot","year":"2017","journal-title":"BioRxiv"},{"key":"ref83","article-title":"Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States","volume":"12","author":"KLM Rudolph","year":"2016","journal-title":"PLoS Genet"},{"key":"ref84","unstructured":"Chollet F, others. Keras. GitHub; 2015."},{"key":"ref85","doi-asserted-by":"crossref","first-page":"13","DOI":"10.25080\/Majora-8b375195-003","article-title":"Hyperopt: A python library for optimizing the hyperparameters of machine learning algorithms","author":"J Bergstra","year":"2013","journal-title":"12th PYTHON Sci CONF (SCIPY 2013)"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"D116","DOI":"10.1093\/nar\/gkv1249","article-title":"HOCOMOCO: Expansion and enhancement of the collection of transcription factor binding sites models","volume":"44","author":"I V Kulakovskiy","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref87","first-page":"2196","article-title":"LS-GKM: A new gkm-SVM for large-scale datasets","volume":"32","author":"D Lee","year":"2016"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1006484","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:33:27Z","timestamp":1768318407000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006484"}},"subtitle":[],"editor":[{"given":"Jian","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,10,4]]},"references-count":87,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1006484","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/110676","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,4]]}}}