{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:47:20Z","timestamp":1790876840419,"version":"4.1.0"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-13-LAB3-0008-01"],"award-info":[{"award-number":["ANR-13-LAB3-0008-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016307","name":"APIS-GENE","doi-asserted-by":"publisher","award":["AP-2018-44"],"award-info":[{"award-number":["AP-2018-44"]}],"id":[{"id":"10.13039\/100016307","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Bull fertility is an important economic trait, and the use of subfertile semen for artificial insemination decreases the global efficiency of the breeding sector. Although the analysis of semen functional parameters can help to identify infertile bulls, no tools are currently available to enable precise predictions and prevent the commercialization of subfertile semen. Because male fertility is a multifactorial phenotype that is dependent on genetic, epigenetic, physiological and environmental factors, we hypothesized that an integrative analysis might help to refine our knowledge and understanding of bull fertility. We combined -omics data (genotypes, sperm DNA methylation at CpGs and sperm small non-coding RNAs) and semen parameters measured on a large cohort of 98 Montb\u00e9liarde bulls with contrasting fertility levels. Multiple Factor Analysis was conducted to study the links between the datasets and fertility. Four methodologies were then considered to identify the features linked to bull fertility variation: Logistic Lasso, Random Forest, Gradient Boosting and Neural Networks. Finally, the features selected by these methods were annotated in terms of genes, to conduct functional enrichment analyses. The less relevant features in -omics data were filtered out, and MFA was run on the remaining 12,006 features, including the 11 semen parameters and a balanced proportion of each type of\u2013omics data. The results showed that unlike the semen parameters studied the\u2013omics datasets were related to fertility. Biomarkers related to bull fertility were selected using the four methodologies mentioned above. The most contributory CpGs, SNPs and miRNAs targeted genes were all found to be involved in development. Interestingly, fragments derived from ribosomal RNAs were overrepresented among the selected features, suggesting roles in male fertility. These markers could be used in the future to identify subfertile bulls in order to increase the global efficiency of the breeding sector.<\/jats:p>","DOI":"10.1371\/journal.pone.0298623","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T19:04:03Z","timestamp":1708715043000},"page":"e0298623","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multi-omics data integration for the identification of biomarkers for bull fertility"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8959-1489","authenticated-orcid":true,"given":"Valentin","family":"Costes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Sellem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Marthey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5900-5506","authenticated-orcid":true,"given":"Chris","family":"Hoze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Schibler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Kiefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Jaffrezic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"issue":"10","key":"pone.0298623.ref001","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.3168\/jds.S0022-0302(06)72430-4","article-title":"Economic Value of Pregnancy in Dairy Cattle1","volume":"89","author":"AD Vries","year":"2006","journal-title":"J Dairy Sci"},{"issue":"9","key":"pone.0298623.ref002","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.theriogenology.2015.07.035","article-title":"Use of combinations of in vitro quality assessments to predict fertility of bovine semen","volume":"84","author":"E Sellem","year":"2015","journal-title":"Theriogenology"},{"issue":"6","key":"pone.0298623.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0065550","article-title":"Detection of Haplotypes Associated with Prenatal Death in Dairy Cattle and Identification of Deleterious Mutations in GART, SHBG and SLC37A2","volume":"8","author":"S Fritz","year":"2013","journal-title":"PLoS ONE"},{"key":"pone.0298623.ref004","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1017\/S1751731114000743","article-title":"Genetics and genomics of reproductive performance in dairy and beef cattle","volume":"8","author":"DP Berry","year":"2014","journal-title":"Anim Int J Anim Biosci"},{"issue":"1","key":"pone.0298623.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.anireprosci.2013.07.002","article-title":"Genomic regions associated with fertility traits in male and female cattle: Advances from microsatellites to high-density chips and beyond","volume":"141","author":"MRS Fortes","year":"2013","journal-title":"Anim Reprod Sci"},{"key":"pone.0298623.ref006","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.theriogenology.2016.08.024","article-title":"Relationship between in vitro sperm functional assessments, seminal plasma composition, and field fertility after AI with either non-sorted or sex-sorted bull semen","volume":"87","author":"SA Holden","year":"2017","journal-title":"Theriogenology"},{"key":"pone.0298623.ref007","doi-asserted-by":"crossref","first-page":"s172","DOI":"10.1017\/S1751731118000599","article-title":"Genomics of Bull Fertility.","volume":"12","author":"JF Taylor","year":"2018","journal-title":"Anim Int J Anim Biosci"},{"key":"pone.0298623.ref008","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1071\/RD21276","article-title":"Sperm-borne sncRNAs: potential biomarkers for semen fertility","volume":"34","author":"E Sellem","year":"2021","journal-title":"Reprod Fertil Dev"},{"issue":"3","key":"pone.0298623.ref009","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.fertnstert.2013.01.124","article-title":"Epigenetic disorders and male subfertility","volume":"99","author":"CC Boissonnas","year":"2013","journal-title":"Fertil Steril"},{"issue":"2","key":"pone.0298623.ref010","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.fertnstert.2011.12.036","article-title":"Epigenetics of the male gamete","volume":"97","author":"DT Carrell","year":"2012","journal-title":"Fertil Steril"},{"issue":"1","key":"pone.0298623.ref011","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1095\/biolreprod.102.015115","article-title":"Protamine 2 Deficiency Leads to Sperm DNA Damage and Embryo Death in Mice1","volume":"69","author":"C Cho","year":"2003","journal-title":"Biol Reprod"},{"issue":"1","key":"pone.0298623.ref012","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/s12864-017-3673-y","article-title":"Male fertility status is associated with DNA methylation signatures in sperm and transcriptomic profiles of bovine preimplantation embryos","volume":"18","author":"J Kropp","year":"2017","journal-title":"BMC Genomics"},{"issue":"5","key":"pone.0298623.ref013","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.theriogenology.2014.06.012","article-title":"Genome-wide profiling of sperm DNA methylation in relation to buffalo (Bubalus bubalis) bull fertility.","volume":"82","author":"A Verma","year":"2014","journal-title":"Theriogenology"},{"issue":"2","key":"pone.0298623.ref014","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1262\/jrd.2020-137","article-title":"Differentially methylated CpG sites related to fertility in Japanese Black bull spermatozoa: epigenetic biomarker candidates to predict sire conception rate","volume":"67","author":"K Takeda","year":"2021","journal-title":"J Reprod Dev"},{"issue":"4","key":"pone.0298623.ref015","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/age.12941","article-title":"Integration of whole-genome DNA methylation data with RNA sequencing data to identify markers for bull fertility","volume":"51","author":"N Gross","year":"2021","journal-title":"Anim Genet"},{"issue":"3","key":"pone.0298623.ref016","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1080\/15592294.2019.1582217","article-title":"Comparative analyses of sperm DNA methylomes among human, mouse and cattle provide insights into epigenomic evolution and complex traits","volume":"14","author":"L Fang","year":"2019","journal-title":"Epigenetics"},{"issue":"3","key":"pone.0298623.ref017","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/mrd.23461","article-title":"Sperm chromatin integrity and DNA methylation in Norwegian Red bulls of contrasting fertility","volume":"88","author":"B Narud","year":"2021","journal-title":"Mol Reprod Dev"},{"issue":"1","key":"pone.0298623.ref018","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13148-022-01275-x","article-title":"Predicting male fertility from the sperm methylome: application to 120 bulls with hundreds of artificial insemination records","volume":"14","author":"V Costes","year":"2022","journal-title":"Clin Epigenetics"},{"issue":"1","key":"pone.0298623.ref019","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1186\/s12864-022-08614-5","article-title":"Sperm DNA methylation patterns at discrete CpGs and genes involved in embryonic development are related to bull fertility","volume":"23","author":"M \u0160tiavnick\u00e1","year":"2022","journal-title":"BMC Genomics"},{"key":"pone.0298623.ref020","doi-asserted-by":"crossref","first-page":"1177932219899051","DOI":"10.1177\/1177932219899051","article-title":"Multi-omics Data Integration, Interpretation, and Its Application.","volume":"14","author":"I Subramanian","year":"2020","journal-title":"Bioinforma Biol Insights"},{"issue":"5","key":"pone.0298623.ref021","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3390\/metabo10050202","article-title":"Metabolomics and Multi-Omics Integration: A Survey of Computational Methods and Resources","volume":"10","author":"T Eicher","year":"2020","journal-title":"Metabolites"},{"issue":"4","key":"pone.0298623.ref022","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1093\/bib\/bbx167","article-title":"Multi-omics integration-a comparison of unsupervised clustering methodologies","volume":"20","author":"G Tini","year":"2019","journal-title":"Brief Bioinform"},{"key":"pone.0298623.ref023","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1016\/j.csbj.2021.06.030","article-title":"Integration strategies of multi-omics data for machine learning analysis","volume":"19","author":"M Picard","year":"2021","journal-title":"Comput Struct Biotechnol J"},{"issue":"6","key":"pone.0298623.ref024","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1016\/j.csda.2007.09.023","article-title":"Multiple factor analysis and clustering of a mixture of quantitative, categorical and frequency data","volume":"52","author":"M Becue-Bertaut","year":"2008","journal-title":"Comput Stat Data Anal"},{"issue":"1","key":"pone.0298623.ref025","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests.","volume":"45","author":"L. Breiman","year":"2001","journal-title":"Mach Learn"},{"key":"pone.0298623.ref026","volume-title":"In: Advances in Neural Information Processing Systems","author":"L Mason","year":"1999"},{"issue":"5","key":"pone.0298623.ref027","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1214\/aos\/1013203451","article-title":"Greedy Function Approximation: A Gradient Boosting Machine","volume":"29","author":"JH Friedman","year":"2001","journal-title":"Ann Stat"},{"issue":"6","key":"pone.0298623.ref028","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1037\/h0042519","article-title":"The Perceptron\u2014a Probabilistic Model for Information-Storage and Organization in the Brain.","volume":"65","author":"F. Rosenblatt","year":"1958","journal-title":"Psychol Rev"},{"issue":"12","key":"pone.0298623.ref029","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"},{"issue":"1","key":"pone.0298623.ref030","first-page":"1","article-title":"FactoMineR: An R package for multivariate analysis.","volume":"25","author":"S Le","year":"2008","journal-title":"J Stat Softw"},{"issue":"1","key":"pone.0298623.ref031","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","article-title":"Regression Shrinkage and Selection Via the Lasso","volume":"58","author":"R. Tibshirani","year":"1996","journal-title":"J R Stat Soc Ser B Methodol"},{"key":"pone.0298623.ref032","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1471-2105-8-25","article-title":"Bias in random forest variable importance measures: Illustrations, sources and a solution","volume":"8","author":"C Strobl","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"pone.0298623.ref033","doi-asserted-by":"crossref","DOI":"10.1201\/9781315139470","volume-title":"Classification And Regression Trees","author":"L Breiman","year":"2017"},{"key":"pone.0298623.ref034","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-21606-5","volume-title":"The Elements of Statistical Learning.","author":"T. Hastie","year":"2001"},{"issue":"10","key":"pone.0298623.ref035","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1109\/5.58337","article-title":"Backpropagation through time: what it does and how to do it","volume":"78","author":"PJ Werbos","year":"1990","journal-title":"Proc IEEE"},{"issue":"02","key":"pone.0298623.ref036","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1142\/S0129065797000227","article-title":"Data Mining of Inputs: Analysing Magnitude and Functional Measures","volume":"08","author":"TD Gedeon","year":"1997","journal-title":"Int J Neural Syst"},{"issue":"8","key":"pone.0298623.ref037","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.patrec.2005.10.010","article-title":"An introduction to ROC analysis","volume":"27","author":"T. Fawcett","year":"2006","journal-title":"Pattern Recognit Lett"},{"key":"pone.0298623.ref038","first-page":"4","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","author":"V Agarwal","year":"2015","journal-title":"eLife"},{"issue":"4","key":"pone.0298623.ref039","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1203\/00006450-199710000-00001","article-title":"Homeobox genes in embryogenesis and pathogenesis","volume":"42","author":"M Mark","year":"1997","journal-title":"Pediatr Res"},{"issue":"3","key":"pone.0298623.ref040","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S0015-0282(16)56590-X","article-title":"Localization of fibronectin on the surface of human spermatozoa and relation to the sperm-egg interaction","volume":"61","author":"K Hoshi","year":"1994","journal-title":"Fertil Steril"},{"issue":"6","key":"pone.0298623.ref041","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/humupd\/dmaa025","article-title":"DNA methylation in human sperm: a systematic review","volume":"26","author":"F \u00c5senius","year":"2020","journal-title":"Hum Reprod Update"},{"issue":"1","key":"pone.0298623.ref042","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA Methylation and Its Basic Function","volume":"38","author":"LD Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"pone.0298623.ref043","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13072-020-00340-0","article-title":"A comprehensive overview of bull sperm-borne small non-coding RNAs and their diversity across breeds","volume":"13","author":"E Sellem","year":"2020","journal-title":"Epigenetics Chromatin"},{"issue":"18","key":"pone.0298623.ref044","first-page":"3458","article-title":"piRNAs: from biogenesis to function","volume":"141","author":"EM Weick","year":"2014","journal-title":"Dev Camb Engl"},{"issue":"4","key":"pone.0298623.ref045","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.devcel.2018.06.024","article-title":"Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice","volume":"46","author":"CC Conine","year":"2018","journal-title":"Dev Cell"},{"key":"pone.0298623.ref046","article-title":"Leakage and the Reproducibility Crisis in ML-based Science.","author":"S Kapoor","year":"2022","journal-title":"arXiv"},{"issue":"9","key":"pone.0298623.ref047","first-page":"3255","article-title":"miRNA 34a, 100, and 137 modulate differentiation of mouse embryonic stem cells","volume":"24","author":"C Tarantino","year":"2010","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"issue":"40","key":"pone.0298623.ref048","doi-asserted-by":"crossref","first-page":"64932","DOI":"10.18632\/oncotarget.10751","article-title":"miR-29 regulates Tet1 expression and contributes to early differentiation of mouse","volume":"7","author":"Y Cui","year":"2016","journal-title":"ESCs. Oncotarget"},{"issue":"1","key":"pone.0298623.ref049","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12864-020-07280-9","article-title":"The micro-RNA content of unsorted cryopreserved bovine sperm and its relation to the fertility of sperm after sex-sorting","volume":"22","author":"E Keles","year":"2021","journal-title":"BMC Genomics"},{"issue":"1","key":"pone.0298623.ref050","doi-asserted-by":"crossref","first-page":"10358","DOI":"10.1038\/s41598-019-46775-8","article-title":"Sperm-borne miR-216b modulates cell proliferation during early embryo development via","volume":"9","author":"MBR Alves","year":"2019","journal-title":"K-RAS. Sci Rep"},{"issue":"2","key":"pone.0298623.ref051","article-title":"Profiling and identification of small rDNA-derived RNAs and their potential biological functions","volume":"8","author":"H Wei","year":"2013","journal-title":"PloS One"},{"key":"pone.0298623.ref052","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41421-019-0087-9","article-title":"Identification of small non-coding RNAs as sperm quality biomarkers for in vitro fertilization","volume":"5","author":"M Hua","year":"2019","journal-title":"Cell Discov"},{"issue":"2","key":"pone.0298623.ref053","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/bies.20528","article-title":"Development and function of the mammalian spleen","volume":"29","author":"A Brendolan","year":"2007","journal-title":"BioEssays News Rev Mol Cell Dev Biol"},{"issue":"1","key":"pone.0298623.ref054","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.bbrc.2005.11.021","article-title":"BARHL1 homeogene, the human ortholog of the mouse Barhl1 involved in cerebellum development, shows regional and cellular specificities in restricted domains of developing human central nervous system","volume":"339","author":"C Lopes","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0298623.ref055","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.mce.2006.12.019","article-title":"Roles of the LHX3 and LHX4 LIM-Homeodomain Factors in Pituitary Development","volume":"265\u2013266","author":"RD Mullen","year":"2007","journal-title":"Mol Cell Endocrinol"},{"issue":"7","key":"pone.0298623.ref056","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1387\/ijdb.062153kb","article-title":"Genetic interaction between Lef1 and Alx4 is required for early embryonic development","volume":"50","author":"K Boras-Granic","year":"2006","journal-title":"Int J Dev Biol"},{"issue":"4","key":"pone.0298623.ref057","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1387\/ijdb.051984lp","article-title":"Genetic interaction of Gli3 and Alx4 during limb development","volume":"49","author":"L Panman","year":"2005","journal-title":"Int J Dev Biol"},{"issue":"19","key":"pone.0298623.ref058","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1101\/gad.921501","article-title":"adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx\/Tlx3","volume":"15","author":"Y Qian","year":"2001","journal-title":"Genes Dev"},{"key":"pone.0298623.ref059","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1471-213X-9-27","article-title":"Mouse H6 Homeobox 1 (Hmx1) mutations cause cranial abnormalities and reduced body mass","volume":"9","author":"RJ Munroe","year":"2009","journal-title":"BMC Dev Biol"},{"issue":"23","key":"pone.0298623.ref060","doi-asserted-by":"crossref","first-page":"10538","DOI":"10.1073\/pnas.1000525107","article-title":"The Mohawk homeobox gene is a critical regulator of tendon differentiation","volume":"107","author":"Y Ito","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0298623.ref061","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mod.2016.11.006","article-title":"Hoxa1 and Hoxb1 are required for pharyngeal arch artery development","volume":"143","author":"M Roux","year":"2017","journal-title":"Mech Dev"},{"issue":"2","key":"pone.0298623.ref062","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1111\/jcmm.14046","article-title":"CXXC5: A novel regulator and coordinator of TGF\u2010\u03b2, BMP and Wnt signaling","volume":"23","author":"X Xiong","year":"2019","journal-title":"J Cell Mol Med"},{"issue":"22","key":"pone.0298623.ref063","doi-asserted-by":"crossref","first-page":"7601","DOI":"10.1128\/MCB.21.22.7601-7606.2001","article-title":"CpG binding protein is crucial for early embryonic development","volume":"21","author":"DL Carlone","year":"2001","journal-title":"Mol Cell Biol"},{"key":"pone.0298623.ref064","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1471-213X-8-52","article-title":"The transcription factor Nfix is essential for normal brain development","volume":"8","author":"CE Campbell","year":"2008","journal-title":"BMC Dev Biol"},{"issue":"1","key":"pone.0298623.ref065","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.gene.2016.07.028","article-title":"An evolutionary, structural and functional overview of the mammalian TEAD1 and TEAD2 transcription factors","volume":"591","author":"A Landin-Malt","year":"2016","journal-title":"Gene"},{"issue":"9","key":"pone.0298623.ref066","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1128\/MCB.15.9.4921","article-title":"ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites","volume":"15","author":"AD Bergemann","year":"1995","journal-title":"Mol Cell Biol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T17:56:41Z","timestamp":1731434201000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298623"}},"subtitle":[],"editor":[{"given":"Nei","family":"Moreira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":66,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0298623","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]}}}