{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T06:13:22Z","timestamp":1770531202327,"version":"3.49.0"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    A spontaneous mutation in the wild type C57BL\/6NTac mouse was discovered that is associated with early-onset histopathologic sequalae typical of thyroid dysplasia. The spontaneous mutation resulted from insertion of a L1 long interspersed nuclear element (LINE-1) into an intron within the Thyroglobulin (\n                    <jats:italic>Tg<\/jats:italic>\n                    ) gene. The mouse genome contains a significant amount of retrotransposon DNA, and these mobile genetic elements routinely change genomic location through retrotransposition, including in germ cells. Analysis of the thyroid transcriptome suggested that the presence of the LINE-1 interferes with the\n                    <jats:italic>Tg<\/jats:italic>\n                    gene splicing, resulting in exclusion of exon 26 from most\n                    <jats:italic>Tg<\/jats:italic>\n                    transcripts in animals homozygous (HOM) for the insertion. The LINE-1 insertion allele of the\n                    <jats:italic>Tg<\/jats:italic>\n                    gene has been designated\n                    <jats:italic>Tg<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>tdys-Tac<\/jats:italic>\n                    <\/jats:sup>\n                    . The resulting phenotype is inherited in an autosomal dominant manner with affected mice exhibiting thyroid follicular cell dysplasia that progresses to thyroid adenoma by 9 months of age with complete penetrance in homozygotes. Serum thyroid hormone measurements revealed a decrease in triiodothyronine (T3) levels in homozygotes at 12 months of age, as well as a decrease in tetraiodothyronine (T4) levels at 6\u20139 months and at 12 months of age in both heterozygotes and homozygotes. In addition, serum Thyroid Stimulating Hormone (TSH) level was strongly increased in homozygotes at 6\u20138 months of age, consistent with hypothyroidism. Computational molecular modeling showed that omission of the 64 amino acids from the TG protein arm domain, which is the consequence of exon 26-skipping in the\n                    <jats:italic>Tg<\/jats:italic>\n                    transcript, results in decreased local stability. This result in combination with the observed up-regulation in unfolded protein response (UPR) pathways in the thyroids of affected animals, identifies the arm domain of TG as important for its proper cellular distribution. This report describes a spontaneous retrotransposon insertion causatively linked to dysregulated physiological phenotypes in a widely used inbred mouse strain.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0325493","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T13:46:32Z","timestamp":1751982392000},"page":"e0325493","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["LINE-1 transposition into murine Thyroglobulin results in congenital thyroid dysplasia"],"prefix":"10.1371","volume":"20","author":[{"given":"Wendy J.","family":"Bailey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-2357","authenticated-orcid":true,"given":"Bart M. G.","family":"Smits","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoltan","family":"Erdos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Gaspar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Lane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabu","family":"Kuruvilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas W.","family":"Rosahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Thudium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingzhou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warren E.","family":"Glaab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"MacGowan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Multari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Cumo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1596-8973","authenticated-orcid":true,"given":"Adam","family":"Navis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Forest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"issue":"1","key":"pone.0325493.ref001","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1210\/er.2015-1090","article-title":"Thyroglobulin from molecular and cellular biology to clinical endocrinology","volume":"37","author":"B Di Jeso","year":"2016","journal-title":"Endocr Rev"},{"issue":"17","key":"pone.0325493.ref002","doi-asserted-by":"crossref","first-page":"17085","DOI":"10.1074\/jbc.M314042200","article-title":"The acetylcholinesterase homology region is essential for normal conformational maturation and secretion of thyroglobulin","volume":"279","author":"Y-N Park","year":"2004","journal-title":"J Biol Chem"},{"issue":"19","key":"pone.0325493.ref003","doi-asserted-by":"crossref","first-page":"12752","DOI":"10.1074\/jbc.M806898200","article-title":"The cholinesterase-like domain, essential in thyroglobulin trafficking for thyroid hormone synthesis, is required for protein dimerization","volume":"284","author":"J Lee","year":"2009","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0325493.ref004","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1677\/joe.0.1260051","article-title":"Mutant gene-induced disorders of structure, function and thyroglobulin synthesis in congenital goitre (cog\/cog) in mice","volume":"126","author":"LR Adkison","year":"1990","journal-title":"J Endocrinol"},{"issue":"11","key":"pone.0325493.ref005","first-page":"4050","article-title":"A novel missense mutation (G2320R) in thyroglobulin causes hypothyroidism in rdw rats","volume":"141","author":"A Hishinuma","year":"2000","journal-title":"Endocrinology"},{"issue":"17","key":"pone.0325493.ref006","doi-asserted-by":"crossref","first-page":"9909","DOI":"10.1073\/pnas.95.17.9909","article-title":"A single amino acid change in the acetylcholinesterase-like domain of thyroglobulin causes congenital goiter with hypothyroidism in the cog\/cog mouse: a model of human endoplasmic reticulum storage diseases","volume":"95","author":"PS Kim","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"pone.0325493.ref007","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1210\/mend.14.12.0571","article-title":"A missense mutation G2320R in the thyroglobulin gene causes non-goitrous congenital primary hypothyroidism in the WIC-rdw rat","volume":"14","author":"PS Kim","year":"2000","journal-title":"Mol Endocrinol"},{"issue":"5","key":"pone.0325493.ref008","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1097\/MED.0b013e32832ff218","article-title":"Mutations of the thyroglobulin gene and its relevance to thyroid disorders","volume":"16","author":"IGS Rubio","year":"2009","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"issue":"23","key":"pone.0325493.ref009","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.1111\/febs.12019","article-title":"Congenital hypothyroidism mutations affect common folding and trafficking in the \u03b1\/\u03b2-hydrolase fold proteins","volume":"279","author":"A De Jaco","year":"2012","journal-title":"FEBS J"},{"issue":"6822","key":"pone.0325493.ref010","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"ES Lander","year":"2001","journal-title":"Nature"},{"issue":"6915","key":"pone.0325493.ref011","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nature01262","article-title":"Initial sequencing and comparative analysis of the mouse genome","volume":"420","author":"Mouse Genome Sequencing Consortium","year":"2002","journal-title":"Nature"},{"issue":"6","key":"pone.0325493.ref012","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0959-437X(99)00031-3","article-title":"Interspersed repeats and other mementos of transposable elements in mammalian genomes","volume":"9","author":"AF Smit","year":"1999","journal-title":"Curr Opin Genet Dev"},{"issue":"10","key":"pone.0325493.ref013","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1101\/gr.388902","article-title":"Retroelement distributions in the human genome: variations associated with age and proximity to genes","volume":"12","author":"P Medstrand","year":"2002","journal-title":"Genome Res"},{"issue":"5","key":"pone.0325493.ref014","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1093\/nar\/gkl027","article-title":"LINE-1 RNA splicing and influences on mammalian gene expression","volume":"34","author":"VP Belancio","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"40","key":"pone.0325493.ref015","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2107933118","article-title":"An L1 retrotransposon insertion-induced deafness mouse model for studying the development and function of the cochlear stria vascularis","volume":"118","author":"C Song","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0325493.ref016","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1006\/geno.1997.4701","article-title":"The molecular basis of the obese mutation in ob2J mice","volume":"42","author":"BC Moon","year":"1997","journal-title":"Genomics"},{"issue":"5","key":"pone.0325493.ref017","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1073\/pnas.90.5.1756","article-title":"Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice","volume":"90","author":"M Adachi","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0325493.ref018","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/0896-6273(94)90265-8","article-title":"The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element","volume":"13","author":"C M\u00fclhardt","year":"1994","journal-title":"Neuron"},{"issue":"4","key":"pone.0325493.ref019","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"B Langmead","year":"2012","journal-title":"Nat Methods"},{"issue":"2","key":"pone.0325493.ref020","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration","volume":"14","author":"H Thorvaldsd\u00f3ttir","year":"2013","journal-title":"Brief Bioinform"},{"issue":"5","key":"pone.0325493.ref021","first-page":"496","article-title":"Evaluation and characterization of congenital hypothyroidism in rdw dwarf rats","volume":"48","author":"M Umezu","year":"1998","journal-title":"Lab Anim Sci"},{"issue":"7796","key":"pone.0325493.ref022","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41586-020-1995-4","article-title":"The structure of human thyroglobulin","volume":"578","author":"F Coscia","year":"2020","journal-title":"Nature"},{"issue":"7873","key":"pone.0325493.ref023","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"J Jumper","year":"2021","journal-title":"Nature"},{"issue":"7792","key":"pone.0325493.ref024","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41586-019-1923-7","article-title":"Improved protein structure prediction using potentials from deep learning","volume":"577","author":"AW Senior","year":"2020","journal-title":"Nature"},{"issue":"20","key":"pone.0325493.ref025","doi-asserted-by":"crossref","first-page":"167208","DOI":"10.1016\/j.jmb.2021.167208","article-title":"AlphaFold and implications for intrinsically disordered proteins","volume":"433","author":"KM Ruff","year":"2021","journal-title":"J Mol Biol"},{"issue":"6","key":"pone.0325493.ref026","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.str.2023.04.005","article-title":"Computational modeling and prediction of deletion mutants","volume":"31","author":"H Woods","year":"2023","journal-title":"Structure"},{"key":"pone.0325493.ref027","doi-asserted-by":"crossref","first-page":"351864","DOI":"10.1155\/2012\/351864","article-title":"TSH and thyrotropic agonists: key actors in thyroid homeostasis","volume":"2012","author":"JW Dietrich","year":"2012","journal-title":"J Thyroid Res"},{"issue":"7","key":"pone.0325493.ref028","doi-asserted-by":"crossref","first-page":"102066","DOI":"10.1016\/j.jbc.2022.102066","article-title":"Maintaining the thyroid gland in mutant thyroglobulin-induced hypothyroidism requires thyroid cell proliferation that must continue in adulthood","volume":"298","author":"X Zhang","year":"2022","journal-title":"J Biol Chem"},{"issue":"12","key":"pone.0325493.ref029","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.169937","article-title":"Perturbation of endoplasmic reticulum proteostasis triggers tissue injury in the thyroid gland","volume":"8","author":"X Zhang","year":"2023","journal-title":"JCI Insight"},{"issue":"9","key":"pone.0325493.ref030","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adj9797","article-title":"Genetic determinants of blood pressure and heart rate identified through ENU-induced mutagenesis with automated meiotic mapping","volume":"10","author":"SK Teixeira","year":"2024","journal-title":"Sci Adv"},{"issue":"3","key":"pone.0325493.ref031","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.cell.2015.09.025","article-title":"Primate-specific ORF0 contributes to retrotransposon-mediated diversity","volume":"163","author":"AM Denli","year":"2015","journal-title":"Cell"},{"key":"pone.0325493.ref032","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13100-019-0162-7","article-title":"Insertion of a chimeric retrotransposon sequence in mouse Axin1 locus causes metastable kinky tail phenotype","volume":"10","author":"Z Wang","year":"2019","journal-title":"Mob DNA"},{"issue":"2","key":"pone.0325493.ref033","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/gtc.12117","article-title":"Insertion of long interspersed element-1 in the Mitf gene is associated with altered neurobehavior of the black-eyed white Mitf(mi-bw) mouse","volume":"19","author":"K Takeda","year":"2014","journal-title":"Genes Cells"},{"key":"pone.0325493.ref034","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1186\/1471-2164-8-392","article-title":"Exonization of active mouse L1s: a driver of transcriptome evolution?","volume":"8","author":"T Zemojtel","year":"2007","journal-title":"BMC Genomics"},{"issue":"13","key":"pone.0325493.ref035","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1093\/hmg\/ddl138","article-title":"Effects of L1 retrotransposon insertion on transcript processing, localization and accumulation: lessons from the retinal degeneration 7 mouse and implications for the genomic ecology of L1 elements","volume":"15","author":"J Chen","year":"2006","journal-title":"Hum Mol Genet"},{"issue":"2","key":"pone.0325493.ref036","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ng0694-136","article-title":"Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion","volume":"7","author":"SF Kingsmore","year":"1994","journal-title":"Nat Genet"},{"issue":"37","key":"pone.0325493.ref037","doi-asserted-by":"crossref","first-page":"31185","DOI":"10.1074\/jbc.M112.375691","article-title":"A retroelement modifies pre-mRNA splicing: the murine Glrb(spa) allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion","volume":"287","author":"K Becker","year":"2012","journal-title":"J Biol Chem"},{"issue":"10","key":"pone.0325493.ref038","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/humu.22383","article-title":"\u03b2-Thalassemia due to intronic LINE-1 insertion in the \u03b2-globin gene (HBB): molecular mechanisms underlying reduced transcript levels of the \u03b2-globin(L1) allele","volume":"34","author":"L Lanikova","year":"2013","journal-title":"Hum Mutat"},{"key":"pone.0325493.ref039","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.3389\/fgene.2019.01399","article-title":"Insertion of LINE-1 retrotransposon inducing exon inversion causes a rotor syndrome phenotype","volume":"10","author":"D Zhou","year":"2020","journal-title":"Front Genet"},{"issue":"6989","key":"pone.0325493.ref040","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/nature02536","article-title":"Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes","volume":"429","author":"JS Han","year":"2004","journal-title":"Nature"},{"key":"pone.0325493.ref041","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13100-019-0157-4","article-title":"Mouse germ line mutations due to retrotransposon insertions","volume":"10","author":"L Gagnier","year":"2019","journal-title":"Mob DNA"},{"issue":"20","key":"pone.0325493.ref042","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1073\/pnas.201407298","article-title":"A computational analysis of sequence features involved in recognition of short introns","volume":"98","author":"LP Lim","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pone.0325493.ref043","article-title":"1,25-hydroxyvitamin D3 decreases endoplasmic reticulum stress-induced inflammatory response in mammary epithelial cells","volume":"15","author":"G Wen","year":"2020","journal-title":"PLoS One"},{"key":"pone.0325493.ref044","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj3440281","article-title":"Calreticulin: one protein, one gene, many functions","author":"M Michalak","year":"1999","journal-title":"Biochem J"},{"issue":"9","key":"pone.0325493.ref045","doi-asserted-by":"crossref","DOI":"10.1093\/glycob\/cwg075","article-title":"The contribution of N-glycans and their processing in the endoplasmic reticulum to glycoprotein biosynthesis","volume":"13","author":"ES Trombetta","year":"2003","journal-title":"Glycobiology"},{"issue":"6896","key":"pone.0325493.ref046","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nature00890","article-title":"E3 ubiquitin ligase that recognizes sugar chains","volume":"418","author":"Y Yoshida","year":"2002","journal-title":"Nature"},{"issue":"10","key":"pone.0325493.ref047","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.3390\/ijms21103468","article-title":"EDEM1 drives misfolded protein degradation via ERAD and exploits ER-phagy as back-up mechanism when ERAD is impaired","volume":"21","author":"M Chiritoiu","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pone.0325493.ref048","article-title":"Heat shock proteins: biological functions, pathological roles, and therapeutic opportunities","volume":"3","author":"C Hu","year":"2022","journal-title":"MedComm (2020)"},{"issue":"6","key":"pone.0325493.ref049","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrm.2017.20","article-title":"The HSP90 chaperone machinery","volume":"18","author":"FH Schopf","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pone.0325493.ref050","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13100-016-0065-9","article-title":"Roles for retrotransposon insertions in human disease","volume":"7","author":"DC Hancks","year":"2016","journal-title":"Mob DNA"},{"issue":"2","key":"pone.0325493.ref051","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s42000-020-00267-x","article-title":"Genetics of primary congenital hypothyroidism-a review","volume":"20","author":"E Kostopoulou","year":"2021","journal-title":"Hormones (Athens)"},{"issue":"4","key":"pone.0325493.ref052","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.3390\/ijms22041726","article-title":"A narrative review of genetic alterations in primary thyroid epithelial cancer","volume":"22","author":"C Romei","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pone.0325493.ref053","doi-asserted-by":"crossref","first-page":"111227","DOI":"10.1016\/j.mce.2021.111227","article-title":"Structure and genetic variants of thyroglobulin: pathophysiological implications","volume":"528","author":"CE Citterio","year":"2021","journal-title":"Mol Cell Endocrinol"},{"key":"pone.0325493.ref054","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13100-016-0070-z","article-title":"Restricting retrotransposons: a review","volume":"7","author":"JL Goodier","year":"2016","journal-title":"Mob DNA"},{"issue":"4","key":"pone.0325493.ref055","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.cell.2024.12.013","article-title":"An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development","volume":"188","author":"ME Oomen","year":"2025","journal-title":"Cell"},{"issue":"1","key":"pone.0325493.ref056","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1365-2567.2005.02119.x","article-title":"Detection of thyroglobulin mRNA as truncated isoform(s) in mouse thymus","volume":"115","author":"HS Li","year":"2005","journal-title":"Immunology"},{"issue":"4","key":"pone.0325493.ref057","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41587-020-0407-5","article-title":"Targeted nanopore sequencing with Cas9-guided adapter ligation","volume":"38","author":"T Gilpatrick","year":"2020","journal-title":"Nat Biotechnol"},{"issue":"18","key":"pone.0325493.ref058","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: pairwise alignment for nucleotide sequences","volume":"34","author":"H Li","year":"2018","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0325493.ref059","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"P Danecek","year":"2021","journal-title":"Gigascience"},{"issue":"9","key":"pone.0325493.ref060","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/s41587-020-0503-6","article-title":"Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes","volume":"38","author":"K Shafin","year":"2020","journal-title":"Nat Biotechnol"},{"issue":"7","key":"pone.0325493.ref061","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005659","article-title":"OpenMM 7: Rapid development of high performance algorithms for molecular dynamics","volume":"13","author":"P Eastman","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"pone.0325493.ref062","author":"P Vingelmann","year":"2020"},{"issue":"5","key":"pone.0325493.ref063","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"D Seeliger","year":"2010","journal-title":"J Comput Aided Mol Des"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T13:46:48Z","timestamp":1751982408000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325493"}},"subtitle":[],"editor":[{"given":"SARBASHRI","family":"BANK","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":63,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0325493","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]}}}