A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0199461 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Cherif Ben Hamda |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6c6e7c5ba85746d2b0c642f073761d35 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-6c6e7c5ba85746d2b0c642f073761d352025-08-20T03:28:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01137e019946110.1371/journal.pone.0199461A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study.Cherif Ben HamdaRaphael SangedaLiberata MwitaAyton MeintjesSiana NkyaSumir PanjiNicola MulderLamia Guizani-TabbaneAlia BenkahlaJulie MakaniKais GhediraH3ABioNet ConsortiumA 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.https://doi.org/10.1371/journal.pone.0199461 |
| spellingShingle | 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 A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study. PLoS ONE |
| title | A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study. |
| title_full | A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study. |
| title_fullStr | A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study. |
| title_full_unstemmed | A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study. |
| title_short | A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study. |
| title_sort | common molecular signature of patients with sickle cell disease revealed by microarray meta analysis and a genome wide association study |
| url | https://doi.org/10.1371/journal.pone.0199461 |
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