{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T02:24:02Z","timestamp":1762050242419,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Howard University startup funds","award":["U100193","DBI 2000296","IIS 1924092","W911NF-20-2-0277","2U54MD007597"],"award-info":[{"award-number":["U100193","DBI 2000296","IIS 1924092","W911NF-20-2-0277","2U54MD007597"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["U100193","DBI 2000296","IIS 1924092","W911NF-20-2-0277","2U54MD007597"],"award-info":[{"award-number":["U100193","DBI 2000296","IIS 1924092","W911NF-20-2-0277","2U54MD007597"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DoD Center of Excellence in AI and Machine Learning (CoE-AIML)","award":["U100193","DBI 2000296","IIS 1924092","W911NF-20-2-0277","2U54MD007597"],"award-info":[{"award-number":["U100193","DBI 2000296","IIS 1924092","W911NF-20-2-0277","2U54MD007597"]}]},{"DOI":"10.13039\/100000002","name":"National Institute on Minority Health and Health Disparities of the National Institutes of Health","doi-asserted-by":"publisher","award":["U100193","DBI 2000296","IIS 1924092","W911NF-20-2-0277","2U54MD007597"],"award-info":[{"award-number":["U100193","DBI 2000296","IIS 1924092","W911NF-20-2-0277","2U54MD007597"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Neurexin-1 (NRXN1) is a membrane protein essential in synapse formation and cell signaling as a cell-adhesion molecule and cell-surface receptor. NRXN1 and its binding partner neuroligin have been associated with deficits in cognition. Recent genetics research has linked NRXN1 missense mutations to increased risk for brain disorders, including schizophrenia (SCZ) and autism spectrum disorder (ASD). Investigation of the structure\u2013function relationship in NRXN1 has proven difficult due to a lack of the experimental full-length membrane protein structure. AlphaFold, a deep learning-based predictor, succeeds in high-quality protein structure prediction and offers a solution for membrane protein model construction. In the study, we applied a computational saturation mutagenesis method to analyze the systemic effects of missense mutations on protein functions in a human NRXN1 structure predicted from AlphaFold and an experimental Bos taurus structure. The folding energy changes were calculated to estimate the effects of the 29,540 mutations of AlphaFold model on protein stability. The comparative study on the experimental and computationally predicted structures shows that these energy changes are highly correlated, demonstrating the reliability of the AlphaFold structure for the downstream bioinformatics analysis. The energy calculation revealed that some target mutations associated with SCZ and ASD could make the protein unstable. The study can provide helpful information for characterizing the disease-causing mutations and elucidating the molecular mechanisms by which the variations cause SCZ and ASD. This methodology could provide the bioinformatics protocol to investigate the effects of target mutations on multiple AlphaFold structures.<\/jats:p>","DOI":"10.3390\/genes13050789","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T12:06:01Z","timestamp":1651147561000},"page":"789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Computational Saturation Mutagenesis to Investigate the Effects of Neurexin-1 Mutations on AlphaFold Structure"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6241-0513","authenticated-orcid":false,"given":"Raina","family":"Rhoades","sequence":"first","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}]},{"given":"Brianna","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1187-1162","authenticated-orcid":false,"given":"Dominique","family":"Prichett","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}]},{"given":"Yayin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Howard University, Washington, DC 20059, USA"}]},{"given":"Shaolei","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard University, Washington, DC 20059, USA"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: Massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_3","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":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.1073\/pnas.0502038102","article-title":"Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter","volume":"102","author":"Nam","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.sbi.2019.01.009","article-title":"Neurexins\u2014Versatile molecular platforms in the synaptic cleft","volume":"54","author":"Rudenko","year":"2019","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1126\/science.1621094","article-title":"Neurexins: Synaptic Cell Surface Proteins Related to the \u03b1-Latrotoxin Receptor and Laminin","volume":"257","author":"Ushkaryov","year":"1992","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1074\/jbc.271.5.2676","article-title":"Structures, alternative splicing, and neurexin binding of multiple neuroligins","volume":"271","author":"Ichtchenko","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0896-6273(95)90306-2","article-title":"Cartography of neurexins: More than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons","volume":"14","author":"Ullrich","year":"1995","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/ajmg.b.31063","article-title":"Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders","volume":"153B","author":"Ching","year":"2010","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Liao, J., Li, Q., Zhang, X., Liu, L., Yan, J., Zhang, D., Yan, H., and Yue, W. (2021). Altered Resting-State Brain Activity in Schizophrenia and Obsessive-Compulsive Disorder Compared with Non-psychiatric Controls: Commonalities and Distinctions Across Disorders. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.681701"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1002\/aur.2576","article-title":"Brain morphology, autistic traits, and polygenic risk for autism: A population-based neuroimaging study","volume":"14","author":"Alemany","year":"2021","journal-title":"Autism Res."},{"key":"ref_12","first-page":"1","article-title":"Functional abnormality in the sensorimotor system attributed to NRXN1 variants in boys with attention deficit hyperactivity disorder","volume":"2021","author":"Zhong","year":"2021","journal-title":"Brain Imaging Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2013-14-9-213","article-title":"Neurexins","volume":"14","author":"Reissner","year":"2013","journal-title":"Genome Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.cell.2017.10.024","article-title":"Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits","volume":"171","year":"2017","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/bs.ircmb.2016.01.002","article-title":"Emergent Synapse Organizers: LAR-RPTPs and Their Companions","volume":"324","author":"Han","year":"2016","journal-title":"Int. Rev. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/mp.2010.134","article-title":"Synaptic modulators Nrxn1 and Nrxn3 are disregulated in a Disc1 mouse model of schizophrenia","volume":"16","author":"Brown","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.conb.2007.01.011","article-title":"Neurexin-neuroligin signaling in synapse development This review comes from a themed issue on Development Edited by Ben Barres and Mu-Ming Poo","volume":"17","author":"Craig","year":"2007","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.str.2011.03.011","article-title":"The Crystal Structure of the \u03b1-Neurexin-1 Extracellular Region Reveals a Hinge Point for Mediating Synaptic Adhesion and Function","volume":"19","author":"Miller","year":"2011","journal-title":"Structure"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0968-0004(01)01832-1","article-title":"LG\/LNS domains: Multiple functions\u2014One business end?","volume":"26","author":"Rudenko","year":"2001","journal-title":"Trends Biochem. Sci."},{"key":"ref_20","first-page":"992","article-title":"Structures of Neuroligin-1 and the Neuroligin-1\/Neurexin-1b Complex Reveal Specific","volume":"2","author":"Boucard","year":"2007","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12969","DOI":"10.1523\/JNEUROSCI.5294-07.2008","article-title":"Polarized Targeting of Neurexins to Synapses Is Regulated by their C-Terminal Sequences","volume":"28","author":"Fairless","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nature01755","article-title":"\u03b1-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis","volume":"423","author":"Missler","year":"2003","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1523\/JNEUROSCI.0497-05.2005","article-title":"Extracellular domains of \u03b1-neurexins participate in regulating synaptic transmission by selectively affecting N- and P\/Q-type Ca2+ channels","volume":"25","author":"Zhang","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8277","DOI":"10.1523\/JNEUROSCI.0511-18.2018","article-title":"\u03b1-Neurexins together with \u03b12\u03b4-1 auxiliary subunits regulate Ca2+ influx through Cav2.1 channels","volume":"38","author":"Brockhaus","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1073\/pnas.0308626100","article-title":"Postsynaptic N-methyl-D-aspartate receptor function requires \u03b1-neurexins","volume":"101","author":"Kattenstroth","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.neuron.2006.09.003","article-title":"Neuroligins Determine Synapse Maturation and Function","volume":"51","author":"Varoqueaux","year":"2006","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0166-2236(02)02152-5","article-title":"Molecular mechanisms of CNS synaptogenesis","volume":"25","author":"Garner","year":"2002","journal-title":"Trends Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nrm1242","article-title":"Some assembly required: The development of neuronal synapses","volume":"4","author":"Li","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/nn1074","article-title":"Neurexin mediates the assembly of presynaptic terminals","volume":"6","author":"Dean","year":"2003","journal-title":"Nat. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0955-0674(03)00107-8","article-title":"Synaptic adhesion molecules","volume":"15","author":"Yamagata","year":"2003","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D313","DOI":"10.1093\/nar\/gkw1132","article-title":"The SWISS-MODEL Repository\u2014New features and functionality","volume":"45","author":"Bienert","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: The universal protein knowledgebase in 2021","volume":"49","author":"Bateman","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0022-2836(70)90057-4","article-title":"A general method applicable to the search for similarities in the amino acid sequence of two proteins","volume":"48","author":"Needleman","year":"1970","journal-title":"J. Mol. Biol."},{"key":"ref_34","unstructured":"Schr\u00f6dinger LLC (2015). The {PyMOL} Molecular Graphics System, Version 1.8., Schr\u00f6dinger, Inc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1093\/bib\/bbaa233","article-title":"Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity","volume":"22","author":"Teng","year":"2021","journal-title":"Brief. Bioinform."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/humu.10212","article-title":"Human Gene Mutation Database (HGMD): 2003 update","volume":"21","author":"Stenson","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","article-title":"Predicting transmembrane protein topology with a hidden markov model: Application to complete genomes","volume":"305","author":"Krogh","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_38","first-page":"175","article-title":"A hidden Markov model for predicting transmembrane helices in protein sequences","volume":"6","author":"Sonnhammer","year":"1998","journal-title":"Proc. Int. Conf. Intell. Syst. Mol. Biol."},{"key":"ref_39","unstructured":"Hallgren, J., Tsirigos, K.D., Pedersen, M.D., Armenteros, J.J.A., Marcatili, P., Nielsen, H., Krogh, A., and Winther, O. (2021, December 10). DeepTMHMM. Available online: https:\/\/biolib.com\/DTU\/DeepTMHMM."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W401","DOI":"10.1093\/nar\/gkv485","article-title":"The TOPCONS web server for consensus prediction of membrane protein topology and signal peptides","volume":"43","author":"Tsirigos","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hecht, M., Bromberg, Y., and Rost, B. (2015). Better prediction of functional effects for sequence variants. BMC Genom., 16.","DOI":"10.1186\/1471-2164-16-S8-S1"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W382","DOI":"10.1093\/nar\/gki387","article-title":"The FoldX web server: An online force field","volume":"33","author":"Schymkowitz","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","article-title":"ConSurf 2016: An improved methodology to estimate and visualize evolutionary conservation in macromolecules","volume":"44","author":"Ashkenazy","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_44","first-page":"1","article-title":"Aminode: Identification of Evolutionary Constraints in the Human Proteome OPEN","volume":"8","author":"Chang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D265","DOI":"10.1093\/nar\/gkz991","article-title":"CDD\/SPARCLE: The conserved domain database in 2020","volume":"48","author":"Lu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/protein\/gzn039","article-title":"CSS-Palm 2.0: An updated software for palmitoylation sites prediction","volume":"21","author":"Ren","year":"2008","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Evans, D.R., Qiao, Y., Trost, B., Calli, K., Martell, S., Jones, S.J.M., Scherer, S.W., and Lewis, M.E.S. (2022). Complex Autism Spectrum Disorder with Epilepsy, Strabismus and Self-Injurious Behaviors in a Patient with a De Novo Heterozygous POLR2A Variant. Genes, 13.","DOI":"10.3390\/genes13030470"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.3390\/cimb43030127","article-title":"Investigation of antidepressant properties of yohimbine by employing structure-based computational assessments","volume":"43","author":"Tasleem","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rotem-Bamberger, S., Fahoum, J., Keinan-Adamsky, K., Tsaban, T., Avraham, O., Shalev, D.E., Chill, J.H., and Schueler-Furman, O. (2021). Tandem WW\/PPxY motif interactions in WWOX: The multifaceted role of the second WW domain. bioRxiv, 12.","DOI":"10.1101\/2021.12.01.470705"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Schweighauser, M., Arseni, D., Bacioglu, M., Huang, M., L\u00f6vestam, S., Shi, Y., Yang, Y., Zhang, W., Kotecha, A., and Garringer, H.J. (2022). Age-dependent formation of TMEM106B amyloid filaments in human brains. Nature, 1\u20138.","DOI":"10.1038\/s41586-022-04650-z"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Carabalona, A., Kallo, H., Andriichuk, L., Gonzalez, M., Elomaa, E., Molinari, F., Fragkou, C., Lappalainen, P., Wessels, M., and Saarikangas, J. (2022). Identification of novel microcephaly-linked protein ABBA that mediates cortical progenitor cell division and corticogenesis through NEDD9-RhoA. medRxiv.","DOI":"10.1101\/2022.03.28.22272122"},{"key":"ref_52","unstructured":"Trinidad, M., Froelich, S., Berguig, G., Wallace, W., Bomba, L., LeBowitz, J.H., Estrada, K., and Wuster, A. (2022). High-throughput discovery of SLC6A1 variants affecting GABA transport in neurological disorders. medRxiv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jpsychires.2021.09.013","article-title":"Rare NRXN1 missense variants identified in autism interfered protein degradation and Drosophila sleeping","volume":"143","author":"Liu","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s11689-020-09325-2","article-title":"Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia","volume":"12","author":"Ishizuka","year":"2020","journal-title":"J. Neurodev. Disord."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1006\/geno.2002.6780","article-title":"Structure and Evolution of Neurexin Genes: Insight into the Mechanism of Alternative Splicing","volume":"79","author":"Tabuchi","year":"2002","journal-title":"Genomics"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sikosek, T., and Chan, H.S. (2014). Biophysics of protein evolution and evolutionary protein biophysics. J. R. Soc. Interface, 11.","DOI":"10.1098\/rsif.2014.0419"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1006\/jsbi.2001.4335","article-title":"Fold Change in Evolution of Protein Structures","volume":"134","author":"Grishin","year":"2001","journal-title":"J. Struct. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ruff, K.M., and Pappu, R.V. (2021). AlphaFold and Implications for Intrinsically Disordered Proteins. J. Mol. Biol., 433.","DOI":"10.1016\/j.jmb.2021.167208"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/ajmg.b.32455","article-title":"The role of protein intrinsic disorder in major psychiatric disorders","volume":"171","author":"Bruxel","year":"2016","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"David, A., Islam, S., Tankhilevich, E., and Sternberg, M.J. (2022). The AlphaFold Database of Protein Structures: A Biologist\u2019s Guide. J. Mol. Biol., 434.","DOI":"10.1016\/j.jmb.2021.167336"},{"key":"ref_61","first-page":"1","article-title":"Ins and outs of AlphaFold2 transmembrane protein structure predictions","volume":"79","author":"Geisler","year":"2022","journal-title":"Experientia"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:03:21Z","timestamp":1760137401000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":61,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["genes13050789"],"URL":"https:\/\/doi.org\/10.3390\/genes13050789","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2022,4,28]]}}}