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Individual transcriptomic studies yield inconsistent differentially expressed genes. To overcome these issues, we demonstrate a methodology to analyze all modern public data. We obtained relevant raw public transcriptomic data from GEO and ENA, then homogeneously processed it (QC, alignment to reference, differential expression analysis). We present a web portal to interactively access the mouse data, and we discovered a commonly perturbed core set of genes that transcends the limitations of any individual study. We then found functionally distinct, consistently up- and downregulated subsets within these genes and some bias to their location. We present this common core of genes as well as focused cores for up, down, cell fraction models, and some tissues. We observed enrichment for this mouse core in other species MeCP2 models and observed overlap with ASD models. By integrating and examining transcriptomic data at scale, we have uncovered the true picture of this dysregulation. The vast scale of these data enables us to analyze signal-to-noise, evaluate a molecular signature in an unbiased manner, and demonstrate a framework for future disease focused informatics work.<\/jats:p>","DOI":"10.3390\/ijms24065122","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T02:30:23Z","timestamp":1678242623000},"page":"5122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics"],"prefix":"10.3390","volume":"24","author":[{"given":"Alexander J.","family":"Trostle","sequence":"first","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian","family":"Li","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Howard Hughes Medical Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiasheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Al-Ouran","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari Krishna","family":"Yalamanchili","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"USDA\/ARS Children\u2019s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhandong","family":"Liu","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Wooi","family":"Wan","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Howard Hughes Medical Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.drudis.2013.10.012","article-title":"Big data in biomedicine","volume":"19","author":"Costa","year":"2014","journal-title":"Drug Discov. 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