{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:10:05Z","timestamp":1792591805315,"version":"4.5.0"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["327509"],"award-info":[{"award-number":["327509"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["335567"],"award-info":[{"award-number":["335567"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["308485"],"award-info":[{"award-number":["308485"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Infertility is assumed to arise exclusively from male- and female-dependent pathological factors. However, recent studies have indicated that reproductive failure may also result from the reproductive incompatibility of the partners. Selection against such incompatibilities likely occurs via female-derived reproductive secretions, including follicular fluid (FF), that mediate gamete-level mate choice towards the sperm of specific males. To facilitate potential development of diagnostic tests for human reproductive incompatibility, we examined whether sperm physiological response to female serum indicate male\u2013female compatibility in the presence of FF. We performed a full-factorial experiment, in which the sperm of 10 males were treated with the FF and serum of 6 healthy females. We found that sperm motility and viability in both biofluids were highly similar and that in 70% of the males, sperm serum treatment predicted male\u2013female compatibility. We also identified male human leucocyte antigen (HLA) alleles and female (FF and serum) anti-HLA antibodies and tested whether the number of allele\u2013antibody matches predict sperm physiological response to female fluids. However, no association was found between measured sperm traits and the number of allele\u2013antibody matches. Overall, the present results may open novel possibilities for the future development of reproductive incompatibility tests and may pave the way towards more accurate infertility diagnostics and treatments.<\/jats:p>","DOI":"10.3390\/ijms23073428","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T14:55:35Z","timestamp":1647960935000},"page":"3428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sperm Physiological Response to Female Serum\u2014Potential New Insights into the Reproductive Incompatibility Diagnostics"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8038-8700","authenticated-orcid":false,"given":"Aleksandra","family":"\u0141ukasiewicz","sequence":"first","affiliation":[{"name":"Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Huhta","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarmo","family":"Ritari","sequence":"additional","affiliation":[{"name":"Research and Development, Finnish Red Cross Blood Service, Haartmaninkatu 8, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Per\u00e4saari","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Allinen","sequence":"additional","affiliation":[{"name":"InOva klinikka Oy, Ajurinkatu 16, 70110 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Malinen","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalaura","family":"Jokiniemi","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8688-2611","authenticated-orcid":false,"given":"Tanja","family":"Turunen","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-4734","authenticated-orcid":false,"given":"Jukka","family":"Partanen","sequence":"additional","affiliation":[{"name":"Research and Development, Finnish Red Cross Blood Service, Haartmaninkatu 8, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Kek\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101 Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","first-page":"20180836","article-title":"Gamete-mediated mate choice: Towards a more inclusive view of sexual selection","volume":"285","author":"Evans","year":"2018","journal-title":"Proc. Biol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrm1893","article-title":"Sperm guidance in mammals\u2014An unpaved road to the egg","volume":"7","author":"Eisenbach","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15321","DOI":"10.1038\/srep15321","article-title":"Lectin staining and flow cytometry reveals female-induced sperm acrosome reaction and surface carbohydrate reorganization","volume":"5","author":"Larma","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1007\/s00018-008-8230-z","article-title":"Control of sperm motility and fertility: Diverse factors and common mechanisms","volume":"65","author":"Yoshida","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1002\/ece3.1977","article-title":"Sperm performance in conspecific and heterospecific female fluid","volume":"6","author":"Cramer","year":"2016","journal-title":"Ecol. Evol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fmolb.2015.00073","article-title":"Characterization of the Olfactory Receptors Expressed in Human Spermatozoa","volume":"2","author":"Flegel","year":"2016","journal-title":"Front. Mol. Biosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1093\/humrep\/dex269","article-title":"Complex CatSper-dependent and independent [Ca2+]i signalling in human spermatozoa induced by follicular fluid","volume":"32","author":"Brown","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/evo.13141","article-title":"Female-induced remote regulation of sperm physiology may provide opportunities for gamete-level mate choice","volume":"71","author":"Evans","year":"2017","journal-title":"Evolution"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00441-005-1127-3","article-title":"Seminal plasma and male factor signalling in the female reproductive tract","volume":"322","author":"Robertson","year":"2005","journal-title":"Cell Tissue Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/molehr\/gav012","article-title":"Do sperm possess a molecular passport? Mechanistic insights into sperm selection in the female reproductive tract","volume":"21","author":"Holt","year":"2015","journal-title":"Mol. Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ebenhard, W.G. (1996). Female Control: Sexual Selection by Cryptic Female Choice, Princeton University Press.","DOI":"10.1515\/9780691207209"},{"key":"ref_12","first-page":"2495","article-title":"Cryptic female preference for genetically unrelated males is mediated by ovarian fluid in the guppy","volume":"278","author":"Gasparini","year":"2011","journal-title":"Proc. Biol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12452","DOI":"10.1038\/ncomms12452","article-title":"Ovarian fluid allows directional cryptic female choice despite external fertilization","volume":"7","author":"Alonzo","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_14","first-page":"20160001","article-title":"Cryptic female choice enhances fertilization success and embryo survival in chinook salmon","volume":"283","author":"Rosengrave","year":"2016","journal-title":"Proc. Biol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20131296","DOI":"10.1098\/rspb.2013.1296","article-title":"Cryptic female choice favours sperm from major histocompatibility complex-dissimilar males","volume":"280","author":"Gillingham","year":"2013","journal-title":"Proc. R. Soc. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4286","DOI":"10.1111\/mec.13222","article-title":"Major histocompatibility complex similarity and sexual selection: Different does not always mean attractive","volume":"24","author":"Gasparini","year":"2015","journal-title":"Mol. Ecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1111\/evo.13591","article-title":"Cryptic haplotype-specific gamete selection yields offspring with optimal MHC immune genes","volume":"72","author":"Lenz","year":"2018","journal-title":"Evolution"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.tree.2017.02.010","article-title":"Postmating Female Control: 20 Years of Cryptic Female Choice","volume":"32","author":"Firman","year":"2017","journal-title":"Trends Ecol. Evol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/mec.13920","article-title":"Patterns of MHC-dependent mate selection in humans and nonhuman primates: A meta-analysis","volume":"26","author":"Winternitz","year":"2017","journal-title":"Mol. Ecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41437-020-0350-8","article-title":"Gamete-level immunogenetic incompatibility in humans\u2013towards deeper understanding of fertilization and infertility?","volume":"125","author":"Jokiniemi","year":"2020","journal-title":"Heredity"},{"key":"ref_21","first-page":"20201682","article-title":"Post-copulatory genetic matchmaking: HLA-dependent effects of cervical mucus on human sperm function","volume":"287","author":"Jokiniemi","year":"2020","journal-title":"Proc. R. Soc. Lond. B Biol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1093\/humrep\/deab221","article-title":"Genetic incompatibility of the reproductive partners: An evolutionary perspective on infertility","volume":"36","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/humupd\/dmx022","article-title":"Temporal trends in sperm count: A systematic review and meta-regression analysis","volume":"23","author":"Levine","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2741\/4208","article-title":"Genetic and molecular diagnostics of male infertility in the clinical practice","volume":"19","author":"Pizzol","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1093\/humupd\/dmv042","article-title":"Sperm selection in natural conception: What can we learn from Mother Nature to improve assisted reproduction outcomes?","volume":"21","author":"Sakkas","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0300-9629(94)90381-6","article-title":"Antithrombin III enhances the motility and chemotaxis of boar sperm","volume":"107","author":"Lee","year":"1994","journal-title":"Comp. Biochem. Physiol. Comp. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/jcp.20734","article-title":"Identification and characterization of a sperm motility promoting glycoprotein from buffalo blood serum","volume":"209","author":"Mandal","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dungdung, S.R., Bhoumik, A., Saha, S., Ghosh, P., Das, K., Mukherjee, S., Nath, D., Chakrabarty, J., Kundu, C., and Jaiswal, B.S. (2016). Sperm Motility Regulatory Proteins: A Tool to Enhance Sperm Quality, IntechOpen.","DOI":"10.5772\/62470"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1530\/REP-09-0177","article-title":"Morphological classification of bovine ovarian follicles","volume":"139","author":"Rodgers","year":"2010","journal-title":"Reproduction"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/S0015-0282(16)57191-X","article-title":"Human serum and follicular fluid stimulate hyperactivation of human spermatozoa after preincubation","volume":"62","author":"Kulin","year":"1994","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1095\/biolreprod58.3.705","article-title":"The Ovarian Blood Follicle Barrier Is Both Charge- and Size-Selective in Mice1","volume":"58","author":"Hess","year":"1998","journal-title":"Biol. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1093\/humrep\/del257","article-title":"Peptide and protein profiles in serum and follicular fluid of women undergoing IVF","volume":"21","author":"Schweigert","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cheng, C.Y. (2013). The Blood-Follicle Barrier (BFB) in Disease and in Ovarian Function. Biology and Regulation of Blood-Tissue Barriers, Springer.","DOI":"10.1007\/978-1-4614-4711-5"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0015-0282(16)38284-X","article-title":"Immunologic studies on human follicular fluid","volume":"22","author":"Menge","year":"1971","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1600-0897.1984.tb00192.x","article-title":"Sperm Antibodies, Immunoglobulins, and Complement in Human Follicular Fluid","volume":"5","author":"Clarke","year":"1984","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1093\/humrep\/deg249","article-title":"Concentrations of carotenoids, retinol and \u03b1-tocopherol in plasma and follicular fluid of women undergoing IVF","volume":"18","author":"Schweigert","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1530\/rep.1.00705","article-title":"Serum and follicular fluid leptin levels are correlated with human embryo quality","volume":"130","author":"Anifandis","year":"2005","journal-title":"Reproduction"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/humrep\/dei369","article-title":"Antiphospholipid antibodies in serum and follicular fluid\u2014Is there a correlation with IVF implantation failure?","volume":"21","author":"Buckingham","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12958-019-0529-0","article-title":"Serum and follicular fluid thyroid hormone levels and assisted reproductive technology outcomes","volume":"17","author":"Cai","year":"2019","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/j.ajpath.2019.06.011","article-title":"The Origin of Follicular Bile Acids in the Human Ovary","volume":"189","author":"Nagy","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R55","DOI":"10.1530\/REP-21-0123","article-title":"The impact of antisperm antibodies on human male reproductive function: An update","volume":"162","author":"Silva","year":"2021","journal-title":"Reproduction"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/humupd\/7.2.113","article-title":"Human reproductive failure I: Immunological factors","volume":"7","author":"Choudhury","year":"2001","journal-title":"Hum. Reprod. Update"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jri.2010.05.006","article-title":"The presence of HLA-antibodies in recurrent miscarriage patients is associated with a reduced chance of a live birth","volume":"87","author":"Nielsen","year":"2010","journal-title":"J. Reprod. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1095\/biolreprod55.3.620","article-title":"Diploid Expression of Human Leukocyte Antigen Class I and Class II Molecules on Spermatozoa and their Cyclic Inverse Correlation with Inhibin Concentration1","volume":"55","author":"Luque","year":"1996","journal-title":"Biol. Reprod."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/01485010050193986","article-title":"Human Leukocyte Antigen Ii Expression in Sperm Cells: Comparison Between Fertile and Infertile Men","volume":"45","author":"Paradisi","year":"2000","journal-title":"Arch. Androl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e1005","DOI":"10.1002\/mgg3.1005","article-title":"The expression of human leukocyte antigen by human ejaculated spermatozoa","volume":"7","author":"Sereshki","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Wan, Q.-H., Zhang, H.-M., and Fang, S.-G. (2019). Reproductive Strategy Inferred from Major Histocompatibility Complex-Based Inter-Individual, Sperm-Egg, and Mother-Fetus Recognitions in Giant Pandas (Ailuropoda melanoleuca). Cells, 8.","DOI":"10.3390\/cells8030257"},{"key":"ref_48","first-page":"20200805","article-title":"Chemical signals from eggs facilitate cryptic female choice in humans","volume":"287","author":"Fitzpatrick","year":"2020","journal-title":"Proc. R. Soc. Lond. B Biol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gardner, D.K., Weissman, A., Howles, C.M., and Shoham, Z. (2018). Textbook of Assisted Reproductive Techniques: Volume 2: Clinical Perspectives, CRC Press. [5th ed.].","DOI":"10.1201\/9781351228237"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.rbmo.2012.02.021","article-title":"Unexplained infertility: An update and review of practice","volume":"24","author":"Ray","year":"2012","journal-title":"Reprod. Biomed. Online"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1111\/jeb.13872","article-title":"Structural dissimilarity of partners\u2019 immune genes increases sperm viability in women\u2019s reproductive tract","volume":"34","author":"Magris","year":"2021","journal-title":"J. Evol. Biol."},{"key":"ref_52","first-page":"91","article-title":"The uterine tubal fluid: Secretion, composition and biological effects","volume":"2","author":"Aguilar","year":"2005","journal-title":"Anim. Reprod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/humrep\/deh657","article-title":"Human sperm chemotaxis: Both the oocyte and its surrounding cumulus cells secrete sperm chemoattractants","volume":"20","author":"Sun","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1073\/pnas.88.7.2840","article-title":"Sperm attraction to a follicular factor(s) correlates with human egg fertilizability","volume":"88","author":"Ralt","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Vieira, L.A., Diana, A., Soriano-\u00dabeda, C., and Mat\u00e1s, C. (2021). Selection of Boar Sperm by Reproductive Biofluids as Chemoattractants. Animals, 11.","DOI":"10.3390\/ani11010053"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S138","DOI":"10.1016\/j.fertnstert.2007.07.444","article-title":"Human follicular fluid-induced acrosome reaction predicts sperm fertilizing ability in vitro","volume":"88","author":"Huang","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/hdy.1996.160","article-title":"Non-random fertilization in mice correlates with the MHC and something else","volume":"77","author":"Wedekind","year":"1996","journal-title":"Heredity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-0897.1993.tb00595.x","article-title":"Lack of Expression of HLA Antigens on Immature Germ Cells from Ejaculates with Antisperm Antibodies","volume":"30","author":"Castilla","year":"1993","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_59","unstructured":"World Health Organization (2021). WHO Laboratory Manual for the Examination and Processing of Human Semen, World Health Organization. [6th ed.]."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1093\/humupd\/4.6.776","article-title":"Hyperactivated motility of human spermatozoa: A review of physiological function and application in assisted reproduction","volume":"4","author":"Kay","year":"1998","journal-title":"Hum. Reprod. Update"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"lqaa030","DOI":"10.1093\/nargab\/lqaa030","article-title":"Increasing accuracy of HLA imputation by a population-specific reference panel in a FinnGen biobank cohort","volume":"2","author":"Ritari","year":"2020","journal-title":"NAR Genom. Bioinform."},{"key":"ref_62","first-page":"192","article-title":"HIBAG\u2014HLA genotype imputation with attribute bagging","volume":"14","author":"Zheng","year":"2014","journal-title":"Pharm. J."},{"key":"ref_63","unstructured":"Hoboken, N.J. (2007). The R Book, Wiley."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. Stat. Softw."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v082.i13","article-title":"lmerTest Package: Tests in Linear Mixed Effects Models","volume":"82","author":"Kuznetsova","year":"2017","journal-title":"J. Stat. Softw."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"378","DOI":"10.32614\/RJ-2017-066","article-title":"Glmm TMB Balances Speed and Flexibility Among Packages for Zero-inflated Generalized Linear Mixed Modeling","volume":"9","author":"Brooks","year":"2017","journal-title":"R J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e1114","DOI":"10.7717\/peerj.1114","article-title":"A comparison of observation-level random effect and Beta-Binomial models for modelling overdispersion in Binomial data in ecology & evolution","volume":"3","author":"Harrison","year":"2015","journal-title":"PeerJ"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.2041-210x.2012.00261.x","article-title":"A general and simple method for obtainingR2 from generalized linear mixed-effects models","volume":"4","author":"Nakagawa","year":"2013","journal-title":"Methods Ecol. Evol."},{"key":"ref_69","unstructured":"Fox, J., and Weisberg, S. (2019). An R Companion to Applied Regression, Sage. [3rd ed.]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3428\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:41:02Z","timestamp":1760136062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":69,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073428"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073428","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,22]]}}}