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A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study

Author

Listed:
  • Cherif Ben Hamda
  • Raphael Sangeda
  • Liberata Mwita
  • Ayton Meintjes
  • Siana Nkya
  • Sumir Panji
  • Nicola Mulder
  • Lamia Guizani-Tabbane
  • Alia Benkahla
  • Julie Makani
  • Kais Ghedira
  • H3ABioNet Consortium

Abstract

A chronic inflammatory state to a large extent explains sickle cell disease (SCD) pathophysiology. Nonetheless, the principal dysregulated factors affecting this major pathway and their mechanisms of action still have to be fully identified and elucidated. Integrating gene expression and genome-wide association study (GWAS) data analysis represents a novel approach to refining the identification of key mediators and functions in complex diseases. Here, we performed gene expression meta-analysis of five independent publicly available microarray datasets related to homozygous SS patients with SCD to identify a consensus SCD transcriptomic profile. The meta-analysis conducted using the MetaDE R package based on combining p values (maxP approach) identified 335 differentially expressed genes (DEGs; 224 upregulated and 111 downregulated). Functional gene set enrichment revealed the importance of several metabolic pathways, of innate immune responses, erythrocyte development, and hemostasis pathways. Advanced analyses of GWAS data generated within the framework of this study by means of the atSNP R package and SIFT tool identified 60 regulatory single-nucleotide polymorphisms (rSNPs) occurring in the promoter of 20 DEGs and a deleterious SNP, affecting CAMKK2 protein function. This novel database of candidate genes, transcription factors, and rSNPs associated with SCD provides new markers that may help to identify new therapeutic targets.

Suggested Citation

  • Cherif Ben Hamda & Raphael Sangeda & Liberata Mwita & Ayton Meintjes & Siana Nkya & Sumir Panji & Nicola Mulder & Lamia Guizani-Tabbane & Alia Benkahla & Julie Makani & Kais Ghedira & H3ABioNet Consor, 2018. "A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study," PLOS ONE, Public Library of Science, vol. 13(7), pages 1-21, July.
    • Handle: RePEc:plo:pone00:0199461
    DOI: 10.1371/journal.pone.0199461
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    References listed on IDEAS

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    1. Smyth Gordon K, 2004. "Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 3(1), pages 1-28, February.
    2. Kerstin Becker & Sabine Siegert & Mohammad Reza Toliat & Juanjiangmeng Du & Ramona Casper & Guido H Dolmans & Paul M Werker & Sigrid Tinschert & Andre Franke & Christian Gieger & Konstantin Strauch & , 2016. "Meta-Analysis of Genome-Wide Association Studies and Network Analysis-Based Integration with Gene Expression Data Identify New Suggestive Loci and Unravel a Wnt-Centric Network Associated with Dupuytr," PLOS ONE, Public Library of Science, vol. 11(7), pages 1-18, July.
    3. Ivan P Gorlov & Gary E Gallick & Olga Y Gorlova & Christopher Amos & Christopher J Logothetis, 2009. "GWAS Meets Microarray: Are the Results of Genome-Wide Association Studies and Gene-Expression Profiling Consistent? Prostate Cancer as an Example," PLOS ONE, Public Library of Science, vol. 4(8), pages 1-5, August.
    4. Adaikalavan Ramasamy & Adrian Mondry & Chris C Holmes & Douglas G Altman, 2008. "Key Issues in Conducting a Meta-Analysis of Gene Expression Microarray Datasets," PLOS Medicine, Public Library of Science, vol. 5(9), pages 1-13, September.
    5. DeConde Robert P & Hawley Sarah & Falcon Seth & Clegg Nigel & Knudsen Beatrice & Etzioni Ruth, 2006. "Combining Results of Microarray Experiments: A Rank Aggregation Approach," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 5(1), pages 1-25, June.
    6. David Moher & Alessandro Liberati & Jennifer Tetzlaff & Douglas G Altman & The PRISMA Group, 2009. "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-6, July.
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