A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics

Trostle, Alexander J.; Li, Lucian; Kim, Seon-Young; Wang, Jiasheng; Al-Ouran, Rami; Yalamanchili, Hari Krishna; Liu, Zhandong; Wan, Ying-Wooi

doi:10.3390/ijms24065122

Open AccessArticle

A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics

by

Alexander J. Trostle

^1,2,†,

Lucian Li

^1,2,†,

Seon-Young Kim

^1,3,

Jiasheng Wang

^1,2,4,

Rami Al-Ouran

^1,2,

Hari Krishna Yalamanchili

^1,2,5,

Zhandong Liu

^1,2,4,* and

Ying-Wooi Wan

^1,3,*

¹

Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA

²

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA

³

Department of Molecular and Human Genetics, Baylor College of Medicine, Howard Hughes Medical Institute, Houston, TX 77030, USA

⁴

Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA

⁵

USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(6), 5122; https://doi.org/10.3390/ijms24065122

Submission received: 15 January 2023 / Revised: 15 February 2023 / Accepted: 16 February 2023 / Published: 7 March 2023

(This article belongs to the Special Issue Molecular Research on Rett Syndrome and Related Disorders 2.0)

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Abstract

Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2′s molecular role. 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.

Keywords: MeCP2; data portal; Rett syndrome; MeCP2 duplication syndrome; RNA-seq; differential expression analysis; meta-analysis; mouse models

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MDPI and ACS Style

Trostle, A.J.; Li, L.; Kim, S.-Y.; Wang, J.; Al-Ouran, R.; Yalamanchili, H.K.; Liu, Z.; Wan, Y.-W. A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics. Int. J. Mol. Sci. 2023, 24, 5122. https://doi.org/10.3390/ijms24065122

AMA Style

Trostle AJ, Li L, Kim S-Y, Wang J, Al-Ouran R, Yalamanchili HK, Liu Z, Wan Y-W. A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics. International Journal of Molecular Sciences. 2023; 24(6):5122. https://doi.org/10.3390/ijms24065122

Chicago/Turabian Style

Trostle, Alexander J., Lucian Li, Seon-Young Kim, Jiasheng Wang, Rami Al-Ouran, Hari Krishna Yalamanchili, Zhandong Liu, and Ying-Wooi Wan. 2023. "A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics" International Journal of Molecular Sciences 24, no. 6: 5122. https://doi.org/10.3390/ijms24065122

APA Style

Trostle, A. J., Li, L., Kim, S.-Y., Wang, J., Al-Ouran, R., Yalamanchili, H. K., Liu, Z., & Wan, Y.-W. (2023). A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics. International Journal of Molecular Sciences, 24(6), 5122. https://doi.org/10.3390/ijms24065122

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A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics

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