{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T17:07:16Z","timestamp":1782580036929,"version":"3.54.5"},"reference-count":70,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000092","name":"National Library of Medicine","doi-asserted-by":"publisher","award":["R25 LM014214"],"award-info":[{"award-number":["R25 LM014214"]}],"id":[{"id":"10.13039\/100000092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rett syndrome (RTT) and MECP2 duplication syndrome, a subtype of autism spectrum disorder (ASD), are neurodevelopmental disorders caused by MeCP2 loss and gain of function, respectively. While MeCP2 is known to regulate transcription through its interaction with methylated DNA and chromatin-associated factors such as topoisomerase II\u03b2 (TOP2\u03b2), the downstream transcriptional consequences of MeCP2 dosage imbalance remain partially characterized. Here, we present a transcriptome-centered analysis of mouse primary cortical neurons subjected to MeCP2 knockdown (KD) or overexpression (OE), which model RTT and ASD-like conditions in parallel. Using a robust computational pipeline integrating generalized linear models with quasi-likelihood F-tests and Magnitude\u2013Altitude Scoring (GLMQL-MAS), we identified differentially expressed genes (DEGs) in KD and OE relative to wild-type (WT) neurons. This study represents a computational analysis of secondary transcriptomic data aimed at nominating candidate genes for future experimental validation. Gene Ontology enrichment revealed both shared and condition-specific biological processes, with KD uniquely affecting neurodevelopmental and stress-response pathways, and OE perturbing extracellular matrix, calcium signaling, and neuroinflammatory processes. To prioritize robust and disease-relevant targets, we applied Cross-MAS and further filtered DEGs by correlation with MeCP2 expression and regulation directional consistency. This yielded 16 high-confidence dosage-sensitive genes that were capable of classifying WT, KD, and OE samples with 100% accuracy using PCA and logistic regression. Among these, RTT-associated candidates such as Plcb1, Gpr161, Mknk2, Rgcc, and Abhd6 were linked to disrupted synaptic signaling and neurogenesis, while ASD-associated genes, including Aim2, Mcm6, Pcdhb9, and Cbs, implicated neuroinflammation and metabolic stress. These findings establish a compact and mechanistically informative set of MeCP2-responsive genes, which enhance our understanding of transcriptional dysregulation in RTT and ASD and nominate molecular markers for future functional validation and therapeutic exploration.<\/jats:p>","DOI":"10.3390\/ijms26189032","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T07:07:18Z","timestamp":1758092838000},"page":"9032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptional Consequences of MeCP2 Knockdown and Overexpression in Mouse Primary Cortical Neurons"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9569-118X","authenticated-orcid":false,"given":"Mostafa","family":"Rezapour","sequence":"first","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine (WFIRM), Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0997-8133","authenticated-orcid":false,"given":"Joshua","family":"Bowser","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2421-8229","authenticated-orcid":false,"given":"Metin Nafi","family":"Gurcan","sequence":"additional","affiliation":[{"name":"Center for Artificial Intelligence Research, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/2040-2392-4-3","article-title":"MeCP2 modulates gene expression pathways in astrocytes","volume":"4","author":"Yasui","year":"2013","journal-title":"Mol. Autism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1172\/JCI78167","article-title":"MECP2 disorders: From the clinic to mice and back","volume":"125","author":"Lombardi","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15114","DOI":"10.1073\/pnas.1618737114","article-title":"DNA methylation in the gene body influences MeCP2-mediated gene repression","volume":"113","author":"Kinde","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113538","DOI":"10.1016\/j.celrep.2023.113538","article-title":"MeCP2 represses the activity of topoisomerase II\u03b2 in long neuronal genes","volume":"42","author":"Nettles","year":"2023","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Papapietro, O., and Nejentsev, S. (2022). Topoisomerase 2\u03b2 and DNA topology during B cell development. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.982870"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.brainres.2007.04.029","article-title":"Role of DNA topoisomerase II\u03b2 in neurite outgrowth","volume":"1154","author":"Meiners","year":"2007","journal-title":"Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1007\/s12035-022-02949-6","article-title":"TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells","volume":"59","author":"Khazeem","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.tins.2017.11.005","article-title":"MeCP2 as an Activator of Gene Expression","volume":"41","author":"Horvath","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1126\/science.1153252","article-title":"MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription","volume":"320","author":"Chahrour","year":"2008","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.molcel.2019.10.033","article-title":"MeCP2 Represses Enhancers through Chromosome Topology-Associated DNA Methylation","volume":"77","author":"Clemens","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Riedmann, C., and Fondufe-Mittendorf, Y.N. (2016). Comparative analysis of linker histone H1, MeCP2, and HMGD1 on nucleosome stability and target site accessibility. Sci. Rep., 6.","DOI":"10.1038\/srep33186"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gulmez Karaca, K., Brito, D.V.C., and Oliveira, A.M.M. (2019). MeCP2: A Critical Regulator of Chromatin in Neurodevelopment and Adult Brain Function. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184577"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/ajmg.a.33184","article-title":"The MECP2 duplication syndrome","volume":"152A","author":"Ramocki","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/ana.21715","article-title":"Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome","volume":"66","author":"Ramocki","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/85899","article-title":"A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome","volume":"27","author":"Guy","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.neuron.2006.09.037","article-title":"Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation","volume":"52","author":"Zhou","year":"2006","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/aur.1262","article-title":"The Behavioral Phenotype in MECP2 Duplication Syndrome: A Comparison With Idiopathic Autism","volume":"6","author":"Peters","year":"2012","journal-title":"Autism Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rezapour, M., Walker, S.J., Ornelles, D.A., McNutt, P.M., Atala, A., and Gurcan, M.N. (2024). Analysis of gene expression dynamics and differential expression in viral infections using generalized linear models and quasi-likelihood methods. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1342328"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rezapour, M., Walker, S.J., Ornelles, D.A., Niazi, M.K.K., McNutt, P.M., Atala, A., and Gurcan, M.N. (2024). A comparative analysis of RNA-Seq and NanoString technologies in deciphering viral infection response in upper airway lung organoids. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1327984"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rezapour, M., Wesolowski, R., and Gurcan, M.N. (2024). Identifying Key Genes Involved in Axillary Lymph Node Metastasis in Breast Cancer Using Advanced RNA-Seq Analysis: A Methodological Approach with GLMQL and MAS. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137306"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rezapour, M., Narayanan, A., and Gurcan, M.N. (2024). Machine Learning Analysis of RNA-Seq Data Identifies Key Gene Signatures and Pathways in Mpox Virus-Induced Gastrointestinal Complications Using Colon Organoid Models. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252011142"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23961","DOI":"10.1038\/s41598-025-09911-1","article-title":"Tracing the evolutionary pathway of SARS-CoV-2 through RNA sequencing analysis","volume":"15","author":"Rezapour","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1098\/rsta.2009.0127","article-title":"Selective inference in complex research","volume":"367","author":"Benjamini","year":"2009","journal-title":"Philos. Trans. R. Soc. A Math. Phys. Eng. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1037\/met0000079","article-title":"Comparing the Pearson and Spearman correlation coefficients across distributions and sample sizes: A tutorial using simulations and empirical data","volume":"21","author":"Gosling","year":"2016","journal-title":"Psychol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/wics.101","article-title":"Principal component analysis","volume":"2","author":"Abdi","year":"2010","journal-title":"WIREs Comp. Stat."},{"key":"ref_28","unstructured":"Gail, M., Krickeberg, K., Samet, J.M., Tsiatis, A., and Wong, W. (2010). Logistic Regression. Logistic Regression: A Self-Learning Text, Statistics for Biology and Health; Springer. [3rd ed.]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jclinepi.2019.02.004","article-title":"A systematic review shows no performance benefit of machine learning over logistic regression for clinical prediction models","volume":"110","author":"Christodoulou","year":"2019","journal-title":"J. Clin. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.freeradbiomed.2015.04.019","article-title":"Exploring the possible link between MeCP2 and oxidative stress in Rett syndrome","volume":"88","author":"Filosa","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cell.2004.09.011","article-title":"CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism","volume":"119","author":"Splawski","year":"2004","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.biopsych.2014.11.020","article-title":"CACNA1D De Novo Mutations in Autism Spectrum Disorders Activate Cav1.3 L-Type Calcium Channels","volume":"77","author":"Pinggera","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e134","DOI":"10.1038\/tp.2012.61","article-title":"Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain","volume":"2","author":"Rose","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8989","DOI":"10.1007\/s11356-020-12255-0","article-title":"Role of metallic pollutants in neurodegeneration: Effects of aluminum, lead, mercury, and arsenic in mediating brain impairment events and autism spectrum disorder","volume":"e28","author":"Kaur","year":"2021","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1152\/physrev.1999.79.4.1283","article-title":"Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor","volume":"79","author":"Heldin","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1101\/gad.1653708","article-title":"Role of platelet-derived growth factors in physiology and medicine","volume":"22","author":"Andrae","year":"2008","journal-title":"Genes Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mam.2018.01.006","article-title":"PDGF\/PDGFR axis in the neural systems","volume":"62","author":"Sil","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1093\/brain\/awab407","article-title":"NPTX1 mutations trigger endoplasmic reticulum stress and cause autosomal dominant cerebellar ataxia","volume":"145","author":"Coutelier","year":"2021","journal-title":"Brain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0896-6273(00)80782-5","article-title":"Synaptic Clustering of AMPA Receptors by the Extracellular Immediate-Early Gene Product Narp","volume":"23","author":"Xu","year":"1999","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kov\u00e1cs, R.\u00c1., Vad\u00e1szi, H., Buly\u00e1ki, \u00c9., T\u00f6r\u00f6k, G., T\u00f3th, V., M\u00e1ty\u00e1s, D., Kun, J., Hunyadi-Guly\u00e1s, \u00c9., Fedor, F.Z., and Csincsi, \u00c1. (2021). Identification of Neuronal Pentraxins as Synaptic Binding Partners of C1q and the Involvement of NP1 in Synaptic Pruning in Adult Mice. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.599771"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jia, Y., Zhang, X., Cai, Y., Yu, H., Cao, G., Dai, E., Kang, R., Tang, D., Hu, N., and Han, L. (2024). OSGIN1 promotes ferroptosis resistance by directly enhancing GCLM activity. Biochem. Biophys. Res. Commun., 740.","DOI":"10.1016\/j.bbrc.2024.151015"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Yamashita, N., Uchiyama, M., Yamagata, R., and Hwang, G.-W. (2024). Methylmercury Induces Apoptosis in Mouse C17.2 Neural Stem Cells through the Induction of OSGIN1 Expression by NRF2. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073886"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1749-6632.2012.06611.x","article-title":"The role of oxidative stress in Rett syndrome: An overview","volume":"1259","author":"Signorini","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Vogelgesang, S., Niebert, S., Renner, U., M\u00f6bius, W., H\u00fclsmann, S., Manzke, T., and Niebert, M. (2017). Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00061"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11396","DOI":"10.1093\/nar\/gky921","article-title":"Modulation of MKNK2 alternative splicing by splice-switching oligonucleotides as a novel approach for glioblastoma treatment","volume":"46","author":"Mogilevsky","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.celrep.2014.03.041","article-title":"Mnk2 Alternative Splicing Modulates the p38-MAPK Pathway and Impacts Ras-Induced Transformation","volume":"7","author":"Maimon","year":"2014","journal-title":"Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s00401-024-02737-7","article-title":"Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex","volume":"147","author":"Scheper","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Amorim, I.S., Lach, G., and Gkogkas, C.G. (2018). The Role of the Eukaryotic Translation Initiation Factor 4E (eIF4E) in Neuropsychiatric Disorders. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00561"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"693","DOI":"10.3727\/096368916X694184","article-title":"Regulator of Cell Cycle (RGCC) Expression during the Progression of Alzheimer\u2019s Disease","volume":"26","author":"Counts","year":"2017","journal-title":"Cell Transplant."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11010-014-2086-3","article-title":"Knockdown of response gene to complement 32 (RGC32) induces apoptosis and inhibits cell growth, migration, and invasion in human lung cancer cells","volume":"394","author":"Xu","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41594-024-01223-8","article-title":"GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway","volume":"31","author":"Hoppe","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neubiorev.2017.01.008","article-title":"Targeting sonic hedgehog signaling in neurological disorders","volume":"74","author":"Patel","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1016\/j.psyneuen.2007.03.017","article-title":"Hedgehog signaling pathway in neural development and disease","volume":"32","author":"Gulino","year":"2007","journal-title":"Psychoneuroendocrinology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1124\/mol.113.087403","article-title":"Structural Insights into Phospholipase C-\u03b2 Function","volume":"84","author":"Lyon","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1111\/j.1460-9568.2009.06696.x","article-title":"Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway","volume":"29","author":"She","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/hipo.22360","article-title":"Excitation\/inhibition imbalance and impaired synaptic inhibition in hippocampal area CA3 of Mecp2 knockout mice","volume":"25","author":"Calfa","year":"2014","journal-title":"Hippocampus"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bbi.2016.03.009","article-title":"Multiple inflammasome complexes are activated in autistic spectrum disorders","volume":"57","author":"Saresella","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/08039488.2017.1410570","article-title":"A study of single nucleotide polymorphisms in CD157, AIM2 and JARID2 genes in Han Chinese children with autism spectrum disorder","volume":"72","author":"Mo","year":"2017","journal-title":"Nord. J. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1007\/s00439-023-02569-7","article-title":"De novo MCM6 variants in neurodevelopmental disorders: A recognizable phenotype related to zinc binding residues","volume":"142","author":"Smits","year":"2023","journal-title":"Hum. Genet."},{"key":"ref_61","unstructured":"Simons Foundation Autism Research Initiative (2025, July 02). MCM6 Gene\u2014SFARI Gene. Available online: https:\/\/gene.sfari.org\/database\/human-gene\/MCM6."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neuron.2012.09.020","article-title":"Endocannabinoid Signaling and Synaptic Function","volume":"76","author":"Castillo","year":"2012","journal-title":"Neuron"},{"key":"ref_63","first-page":"20","article-title":"Association of Cystathionine Beta Synthase Gene Polymorphism With Cognitive Disorders in Autistic Children","volume":"4","author":"Mohammed","year":"2017","journal-title":"J. Innov. Pharm. Biol. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/mp.2010.136","article-title":"Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis","volume":"17","author":"Rossignol","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"370","DOI":"10.2307\/2344614","article-title":"Generalized Linear Models","volume":"135","author":"Nelder","year":"1972","journal-title":"J. R. Stat. Soc. Ser. A"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wedderburn, R.W.M. (1974). Quasi-Likelihood Functions, Generalized Linear Models, and the Gauss-Newton Method. Biometrika, 61.","DOI":"10.2307\/2334725"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Rezapour, M., Walker, S.J., Ornelles, D.A., Niazi, M.K.K., McNutt, P.M., Atala, A., Gurcan, M.N., and Choi, Y.H. (2024). Exploring the host response in infected lung organoids using NanoString technology: A statistical analysis of gene expression data. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0308849"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Rezapour, M., Niazi, M.K.K., Lu, H., Narayanan, A., and Gurcan, M.N. (2024). Machine learning-based analysis of Ebola virus\u2019 impact on gene expression in nonhuman primates. Front. Artif. Intell., 7.","DOI":"10.3389\/frai.2024.1405332"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Law, C.W., Chen, Y., Shi, W., and Smyth, G.K. (2014). Voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol., 15.","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Robinson, M.D., and Oshlack, A. (2010). A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol., 11.","DOI":"10.1186\/gb-2010-11-3-r25"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9032\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:48Z","timestamp":1760035608000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":70,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26189032"],"URL":"https:\/\/doi.org\/10.3390\/ijms26189032","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]}}}