A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study
Identifieur interne : 000474 ( Main/Exploration ); précédent : 000473; suivant : 000475A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study
Auteurs : Cherif Ben Hamda [Tunisie] ; Raphael Sangeda [Tanzanie] ; Liberata Mwita [Tanzanie] ; Ayton Meintjes [Afrique du Sud] ; Siana Nkya [Tanzanie] ; Sumir Panji [Afrique du Sud] ; Nicola Mulder [Afrique du Sud] ; Lamia Guizani-Tabbane [Tunisie] ; Alia Benkahla [Tunisie] ; Julie Makani [Tunisie] ; Kais Ghedira [Tunisie]Source :
- PLoS ONE [ 1932-6203 ] ; 2018.
Descripteurs français
- KwdFr :
- Allèles (MeSH), Analyse de profil d'expression de gènes (MeSH), Bases de données génétiques (MeSH), Biologie informatique (méthodes), Drépanocytose (génétique), Fouille de données (MeSH), Gene Ontology (MeSH), Génotype (MeSH), Humains (MeSH), Polymorphisme de nucléotide simple (MeSH), Réseaux de régulation génique (MeSH), Transcriptome (MeSH), Étude d'association pangénomique (MeSH).
- MESH :
- génétique : Drépanocytose.
- méthodes : Biologie informatique.
- Allèles, Analyse de profil d'expression de gènes, Bases de données génétiques, Fouille de données, Gene Ontology, Génotype, Humains, Polymorphisme de nucléotide simple, Réseaux de régulation génique, Transcriptome, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Alleles (MeSH), Anemia, Sickle Cell (genetics), Computational Biology (methods), Data Mining (MeSH), Databases, Genetic (MeSH), Gene Expression Profiling (MeSH), Gene Ontology (MeSH), Gene Regulatory Networks (MeSH), Genome-Wide Association Study (MeSH), Genotype (MeSH), Humans (MeSH), Polymorphism, Single Nucleotide (MeSH), Transcriptome (MeSH).
- MESH :
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.
Url:
DOI: 10.1371/journal.pone.0199461
PubMed: 29979707
PubMed Central: 6034806
Affiliations:
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Le document en format XML
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Liberata" uniqKey="Mwita L" first="Liberata" last="Mwita">Liberata Mwita</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania</addr-line></nlm:aff><country xml:lang="fr">Tanzanie</country><wicri:regionArea>Muhimbili University of Health and Allied Sciences, Dar es Salaam</wicri:regionArea></affiliation></author><author><name sortKey="Meintjes, Ayton" sort="Meintjes, Ayton" uniqKey="Meintjes A" first="Ayton" last="Meintjes">Ayton Meintjes</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>University of Cape Town, Cape Town, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>University of Cape Town, Cape Town</wicri:regionArea></affiliation></author><author><name sortKey="Nkya, Siana" sort="Nkya, Siana" uniqKey="Nkya S" first="Siana" last="Nkya">Siana Nkya</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania</addr-line></nlm:aff><country xml:lang="fr">Tanzanie</country><wicri:regionArea>Muhimbili University of Health and Allied Sciences, Dar es Salaam</wicri:regionArea></affiliation></author><author><name sortKey="Panji, Sumir" sort="Panji, Sumir" uniqKey="Panji S" first="Sumir" last="Panji">Sumir Panji</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>University of Cape Town, Cape Town, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>University of Cape Town, Cape Town</wicri:regionArea></affiliation></author><author><name sortKey="Mulder, Nicola" sort="Mulder, Nicola" uniqKey="Mulder N" first="Nicola" last="Mulder">Nicola Mulder</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>University of Cape Town, Cape Town, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>University of Cape Town, Cape Town</wicri:regionArea></affiliation></author><author><name sortKey="Guizani Tabbane, Lamia" sort="Guizani Tabbane, Lamia" uniqKey="Guizani Tabbane L" first="Lamia" last="Guizani-Tabbane">Lamia Guizani-Tabbane</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>University of Tunis El Manar, Tunis, Tunisia</addr-line></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Tunis El Manar, Tunis</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institute Pasteur of Tunis, Tunis, Tunisia</addr-line></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institute Pasteur of Tunis, Tunis</wicri:regionArea></affiliation></author><author><name sortKey="Benkahla, Alia" sort="Benkahla, Alia" uniqKey="Benkahla A" first="Alia" last="Benkahla">Alia Benkahla</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Laboratory of Bioinformatics, Biomathematics and Biostatistics, Institute Pasteur of Tunis, Tunis, Tunisia</addr-line></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>Laboratory of Bioinformatics, Biomathematics and Biostatistics, Institute Pasteur of Tunis, Tunis</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>University of Tunis El Manar, Tunis, Tunisia</addr-line></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Tunis El Manar, Tunis</wicri:regionArea></affiliation></author><author><name sortKey="Makani, Julie" sort="Makani, Julie" uniqKey="Makani J" first="Julie" last="Makani">Julie Makani</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Faculty of Science of Bizerte, Jarzouna, University of Carthage, Tunisia</addr-line></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>Faculty of Science of Bizerte, Jarzouna, University of Carthage</wicri:regionArea></affiliation></author><author><name sortKey="Ghedira, Kais" sort="Ghedira, Kais" uniqKey="Ghedira K" first="Kais" last="Ghedira">Kais Ghedira</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Laboratory of Bioinformatics, Biomathematics and Biostatistics, Institute Pasteur of Tunis, Tunis, Tunisia</addr-line></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>Laboratory of Bioinformatics, Biomathematics and Biostatistics, Institute Pasteur of Tunis, Tunis</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>University of Tunis El Manar, Tunis, Tunisia</addr-line></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Tunis El Manar, Tunis</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alleles (MeSH)</term><term>Anemia, Sickle Cell (genetics)</term><term>Computational Biology (methods)</term><term>Data Mining (MeSH)</term><term>Databases, Genetic (MeSH)</term><term>Gene Expression Profiling (MeSH)</term><term>Gene Ontology (MeSH)</term><term>Gene Regulatory Networks (MeSH)</term><term>Genome-Wide Association Study (MeSH)</term><term>Genotype (MeSH)</term><term>Humans (MeSH)</term><term>Polymorphism, Single Nucleotide (MeSH)</term><term>Transcriptome (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Allèles (MeSH)</term><term>Analyse de profil d'expression de gènes (MeSH)</term><term>Bases de données génétiques (MeSH)</term><term>Biologie informatique (méthodes)</term><term>Drépanocytose (génétique)</term><term>Fouille de données (MeSH)</term><term>Gene Ontology (MeSH)</term><term>Génotype (MeSH)</term><term>Humains (MeSH)</term><term>Polymorphisme de nucléotide simple (MeSH)</term><term>Réseaux de régulation génique (MeSH)</term><term>Transcriptome (MeSH)</term><term>Étude d'association pangénomique (MeSH)</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Anemia, Sickle Cell</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Drépanocytose</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Computational Biology</term></keywords><keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Biologie informatique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Alleles</term><term>Data Mining</term><term>Databases, Genetic</term><term>Gene Expression Profiling</term><term>Gene Ontology</term><term>Gene Regulatory Networks</term><term>Genome-Wide Association Study</term><term>Genotype</term><term>Humans</term><term>Polymorphism, Single Nucleotide</term><term>Transcriptome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Allèles</term><term>Analyse de profil d'expression de gènes</term><term>Bases de données génétiques</term><term>Fouille de données</term><term>Gene Ontology</term><term>Génotype</term><term>Humains</term><term>Polymorphisme de nucléotide simple</term><term>Réseaux de régulation génique</term><term>Transcriptome</term><term>Étude d'association pangénomique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Piel, Fb" uniqKey="Piel F">FB Piel</name></author><author><name sortKey="Patil, Ap" uniqKey="Patil A">AP Patil</name></author><author><name sortKey="Howes, Re" uniqKey="Howes R">RE Howes</name></author><author><name sortKey="Nyangiri, Oa" uniqKey="Nyangiri O">OA Nyangiri</name></author><author><name sortKey="Gething, Pw" uniqKey="Gething P">PW Gething</name></author><author><name sortKey="Dewi, M" uniqKey="Dewi M">M Dewi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baralle, F" uniqKey="Baralle F">F Baralle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Browning, Ja" uniqKey="Browning J">JA 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uniqKey="Noeldner P">PK Noeldner</name></author><author><name sortKey="Lin, F" uniqKey="Lin F">F Lin</name></author><author><name sortKey="Arvai, S" uniqKey="Arvai S">S Arvai</name></author><author><name sortKey="Means, Ar" uniqKey="Means A">AR Means</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Afrique du Sud</li><li>Tanzanie</li><li>Tunisie</li></country></list><tree><country name="Tunisie"><noRegion><name sortKey="Ben Hamda, Cherif" sort="Ben Hamda, Cherif" uniqKey="Ben Hamda C" first="Cherif" last="Ben Hamda">Cherif Ben Hamda</name></noRegion><name sortKey="Ben Hamda, Cherif" sort="Ben Hamda, Cherif" uniqKey="Ben Hamda C" first="Cherif" last="Ben Hamda">Cherif Ben Hamda</name><name sortKey="Ben Hamda, Cherif" sort="Ben Hamda, Cherif" uniqKey="Ben Hamda C" first="Cherif" last="Ben Hamda">Cherif Ben Hamda</name><name sortKey="Benkahla, Alia" sort="Benkahla, Alia" uniqKey="Benkahla A" first="Alia" last="Benkahla">Alia Benkahla</name><name sortKey="Benkahla, Alia" sort="Benkahla, Alia" uniqKey="Benkahla A" first="Alia" last="Benkahla">Alia Benkahla</name><name sortKey="Ghedira, Kais" sort="Ghedira, Kais" uniqKey="Ghedira K" first="Kais" last="Ghedira">Kais Ghedira</name><name sortKey="Ghedira, Kais" sort="Ghedira, Kais" uniqKey="Ghedira K" first="Kais" last="Ghedira">Kais Ghedira</name><name sortKey="Guizani Tabbane, Lamia" sort="Guizani Tabbane, Lamia" uniqKey="Guizani Tabbane L" first="Lamia" last="Guizani-Tabbane">Lamia Guizani-Tabbane</name><name sortKey="Guizani Tabbane, Lamia" sort="Guizani Tabbane, Lamia" uniqKey="Guizani Tabbane L" first="Lamia" last="Guizani-Tabbane">Lamia Guizani-Tabbane</name><name sortKey="Makani, Julie" sort="Makani, Julie" uniqKey="Makani J" first="Julie" last="Makani">Julie Makani</name></country><country name="Tanzanie"><noRegion><name sortKey="Sangeda, Raphael" sort="Sangeda, Raphael" uniqKey="Sangeda R" first="Raphael" last="Sangeda">Raphael Sangeda</name></noRegion><name sortKey="Mwita, Liberata" sort="Mwita, Liberata" uniqKey="Mwita L" first="Liberata" last="Mwita">Liberata Mwita</name><name sortKey="Nkya, Siana" sort="Nkya, Siana" uniqKey="Nkya S" first="Siana" last="Nkya">Siana Nkya</name></country><country name="Afrique du Sud"><noRegion><name sortKey="Meintjes, Ayton" sort="Meintjes, Ayton" uniqKey="Meintjes A" first="Ayton" last="Meintjes">Ayton Meintjes</name></noRegion><name sortKey="Mulder, Nicola" sort="Mulder, Nicola" uniqKey="Mulder N" first="Nicola" last="Mulder">Nicola Mulder</name><name sortKey="Panji, Sumir" sort="Panji, Sumir" uniqKey="Panji S" first="Sumir" last="Panji">Sumir Panji</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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