{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:53:32Z","timestamp":1790780012976,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T00:00:00Z","timestamp":1558483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R21AI135178"],"award-info":[{"award-number":["1R21AI135178"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1007787","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T13:36:44Z","timestamp":1558532204000},"page":"e1007787","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":111,"title":["Circuit diversification in a biofilm regulatory network"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-9698","authenticated-orcid":true,"given":"Manning Y.","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6261-3468","authenticated-orcid":true,"given":"Carol A.","family":"Woolford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"May","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6605-2642","authenticated-orcid":true,"given":"C. Joel","family":"McManus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0868-4000","authenticated-orcid":true,"given":"Aaron P.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrg3891","article-title":"The role of regulatory variation in complex traits and disease","volume":"16","author":"FW Albert","year":"2015","journal-title":"Nat Rev Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s00294-018-0835-7","article-title":"Genetic background effects in quantitative genetics: gene-by-system interactions","volume":"64","author":"M Sardi","year":"2018","journal-title":"Curr Genet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.crvi.2016.04.006","article-title":"Beyond the simplicity of Mendelian inheritance","volume":"339","author":"J Schacherer","year":"2016","journal-title":"C R Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1126\/science.1189015","article-title":"Genotype to phenotype: a complex problem","volume":"328","author":"RD Dowell","year":"2010","journal-title":"Science"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1126\/science.1224339","article-title":"Global gene deletion analysis exploring yeast filamentous growth","volume":"337","author":"O Ryan","year":"2012","journal-title":"Science"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cell.2015.06.037","article-title":"Natural Variation in Gene Expression Modulates the Severity of Mutant Phenotypes","volume":"162","author":"V Vu","year":"2015","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.tig.2015.12.003","article-title":"The Power of Natural Variation for Model Organism Biology","volume":"32","author":"AP Gasch","year":"2016","journal-title":"Trends Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1534\/genetics.112.145573","article-title":"Genetic variation in Saccharomyces cerevisiae: circuit diversification in a signal transduction network","volume":"192","author":"BL Chin","year":"2012","journal-title":"Genetics"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.mib.2017.10.020","article-title":"Fungal interactions with the human host: exploring the spectrum of symbiosis","volume":"40","author":"RA Hall","year":"2017","journal-title":"Curr Opin Microbiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4161\/viru.22913","article-title":"Candida albicans pathogenicity mechanisms","volume":"4","author":"FL Mayer","year":"2013","journal-title":"Virulence"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nrmicro2636","article-title":"Growth of Candida albicans hyphae","volume":"9","author":"PE Sudbery","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"ref12","article-title":"Fungal biofilms, drug resistance, and recurrent infection","author":"JV Desai","year":"2014","journal-title":"Cold Spring Harb Perspect Med 4"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1128\/EC.00163-12","article-title":"Expression of UME6, a key regulator of Candida albicans hyphal development, enhances biofilm formation via Hgc1- and Sun41-dependent mechanisms","volume":"12","author":"M Banerjee","year":"2013","journal-title":"Eukaryot Cell"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1365-2958.2012.08127.x","article-title":"BRG1 and NRG1 form a novel feedback circuit regulating Candida albicans hypha formation and virulence","volume":"85","author":"IA Cleary","year":"2012","journal-title":"Mol Microbiol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e29707","DOI":"10.1371\/journal.pone.0029707","article-title":"Roles of Candida albicans Gat2, a GATA-type zinc finger transcription factor, in biofilm formation, filamentous growth and virulence","volume":"7","author":"H Du","year":"2012","journal-title":"PLoS One"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.cell.2011.10.048","article-title":"A recently evolved transcriptional network controls biofilm development in Candida albicans","volume":"148","author":"CJ Nobile","year":"2012","journal-title":"Cell"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.cub.2005.05.047","article-title":"Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p","volume":"15","author":"CJ Nobile","year":"2005","journal-title":"Curr Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1574-6968.2002.tb11330.x","article-title":"The filamentation pathway controlled by the Efg1 regulator protein is required for normal biofilm formation and development in Candida albicans","volume":"214","author":"G Ramage","year":"2002","journal-title":"FEMS Microbiol Lett"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrmicro.2017.107","article-title":"Development and regulation of single- and multi-species Candida albicans biofilms","volume":"16","author":"MB Lohse","year":"2018","journal-title":"Nat Rev Microbiol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1111\/j.1365-2958.2007.05759.x","article-title":"Heterozygosity of genes on the sex chromosome regulates Candida albicans virulence","volume":"64","author":"W Wu","year":"2007","journal-title":"Mol Microbiol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1101\/gr.174623.114","article-title":"Genetic and phenotypic intra-species variation in Candida albicans","volume":"25","author":"MP Hirakawa","year":"2015","journal-title":"Genome Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1128\/EC.00181-13","article-title":"Characterization of biofilm formation and the role of BCR1 in clinical isolates of Candida parapsilosis","volume":"13","author":"S Pannanusorn","year":"2014","journal-title":"Eukaryot Cell"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/j.1365-2958.2011.07837.x","article-title":"Target specificity of the Candida albicans Efg1 regulator","volume":"82","author":"T Lassak","year":"2011","journal-title":"Mol Microbiol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1091\/mbc.e03-11-0782","article-title":"APSES proteins regulate morphogenesis and metabolism in Candida albicans","volume":"15","author":"T Doedt","year":"2004","journal-title":"Mol Biol Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1128\/EC.00314-07","article-title":"Requirement for Candida albicans Sun41 in biofilm formation and virulence","volume":"6","author":"CT Norice","year":"2007","journal-title":"Eukaryot Cell"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1128\/EC.00285-07","article-title":"Candida albicans Sun41p, a putative glycosidase, is involved in morphogenesis, cell wall biogenesis, and biofilm formation","volume":"6","author":"E Hiller","year":"2007","journal-title":"Eukaryot Cell"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1099\/mic.0.25932-0","article-title":"Quantitative variation of biofilms among strains in natural populations of Candida albicans","volume":"149","author":"X Li","year":"2003","journal-title":"Microbiology"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1128\/EC.00387-08","article-title":"Property differences among the four major Candida albicans strain clades","volume":"8","author":"DM MacCallum","year":"2009","journal-title":"Eukaryot Cell"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1038\/s41467-018-04787-4","article-title":"Gene flow contributes to diversification of the major fungal pathogen Candida albicans","volume":"9","author":"J Ropars","year":"2018","journal-title":"Nat Commun"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"4490","DOI":"10.1091\/mbc.e04-02-0144","article-title":"Transcription profiling of cyclic AMP signaling in Candida albicans","volume":"15","author":"D Harcus","year":"2004","journal-title":"Mol Biol Cell"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e256","DOI":"10.1371\/journal.pbio.0050256","article-title":"Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans","volume":"5","author":"RE Zordan","year":"2007","journal-title":"PLoS Biol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1046\/j.1365-2958.2003.03300.x","article-title":"EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays","volume":"47","author":"K Sohn","year":"2003","journal-title":"Mol Microbiol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.cub.2007.05.017","article-title":"Transcriptional rewiring of fungal galactose-metabolism circuitry","volume":"17","author":"M Martchenko","year":"2007","journal-title":"Curr Biol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"e1000294","DOI":"10.1371\/journal.ppat.1000294","article-title":"The protein kinase Tor1 regulates adhesin gene expression in Candida albicans","volume":"5","author":"RJ Bastidas","year":"2009","journal-title":"PLoS Pathog"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"00050","DOI":"10.1128\/mSphere.00050-17","article-title":"Marker Recycling in Candida albicans through CRISPR-Cas9-Induced Marker Excision","volume":"2","author":"MY Huang","year":"2017","journal-title":"mSphere"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0378-1119(79)90004-0","article-title":"Sterile host yeasts (SHY): a eukaryotic system of biological containment for recombinant DNA experiments","volume":"8","author":"D Botstein","year":"1979","journal-title":"Gene"},{"key":"ref37","article-title":"Candida albicans Gene Deletion with a Transient CRISPR-Cas9 System","volume":"1","author":"K Min","year":"2016","journal-title":"mSphere"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/yea.1552","article-title":"The spectrum of Trp- mutants isolated as 5-fluoroanthranilate-resistant clones in Saccharomyces bayanus, S. mikatae and S. paradoxus","volume":"25","author":"EW Jones","year":"2008","journal-title":"Yeast"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"e1500248","DOI":"10.1126\/sciadv.1500248","article-title":"A Candida albicans CRISPR system permits genetic engineering of essential genes and gene families","volume":"1","author":"VK Vyas","year":"2015","journal-title":"Sci Adv"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1111\/j.1462-5822.2008.01198.x","article-title":"Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions","volume":"10","author":"CJ Nobile","year":"2008","journal-title":"Cell Microbiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"00169","DOI":"10.1128\/mSphere.00169-18","article-title":"Rapid Gene Concatenation for Genetic Rescue of Multigene Mutants in Candida albicans","volume":"3","author":"MY Huang","year":"2018","journal-title":"mSphere"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.mib.2017.12.008","article-title":"Microscopy of fungal biofilms","volume":"43","author":"K Lagree","year":"2018","journal-title":"Curr Opin Microbiol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e1006487","DOI":"10.1371\/journal.pgen.1006487","article-title":"Bypass of Candida albicans Filamentation\/Biofilm Regulators through Diminished Expression of Protein Kinase Cak1","volume":"12","author":"CA Woolford","year":"2016","journal-title":"PLoS Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: discovering splice junctions with RNA-Seq","volume":"25","author":"C Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"AR Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1093\/bioinformatics\/btu048","article-title":"Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases","volume":"30","author":"S Bae","year":"2014","journal-title":"Bioinformatics"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome Res"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1007966","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T00:00:00Z","timestamp":1563494400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1007787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T02:49:24Z","timestamp":1588992564000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1007787"}},"subtitle":[],"editor":[{"given":"Xiaorong","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,5,22]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1007787","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.735813553.793561519","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.735813553.793561950","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,22]]}}}