Gene Expression Analysis Reveals Genes Common to Cerebral Malaria and Neurodegenerative Disorders

Cabantous, Stéphanie; Doumbo, Ogobara K.; Poudiougou, Belco; Louis, Lawrence H.; Barry, Abdoulaye; Oumar, Aboubacar Alassane; Traore, Abdoualye; Marquet, Sandrine; Dessein, Alain

doi:10.1093/infdis/jix359

Cited by 11 publications

(13 citation statements)

References 16 publications

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“…The whole-transcriptome analysis was performed by using the Agilent technology, as previously described [8]. Each microarray contained about 22,700 genes based on RefSeq and 7,419 large intergenic noncoding RNAs.…”

Section: Whole-transcriptome Analysismentioning

confidence: 99%

“…Hence, transcriptomic analysis is a powerful tool that can now be used to realize this previously unattainable goal in the study of complex infectious diseases. Recently, we carried out a study of the transcriptome of CM and UM children, from which we explored only some pathways and genes related to neurodegenerative diseases in order to validate our experimental approach [8]. Herein, we hypothesize that a whole gene expression profiling from peripheral blood may be robust enough to identify a specific molecular RNA signature of CM subjects allowing to elucidate the signaling pathways, gene interaction networks, and upstream regulators playing critical roles in the pathogenesis of CM.…”

Section: Introductionmentioning

confidence: 99%

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Understanding Human Cerebral Malaria through a Blood Transcriptomic Signature: Evidences for Erythrocyte Alteration, Immune/Inflammatory Dysregulation, and Brain Dysfunction

Cabantous

Poudiougou

Bergon

et al. 2020

Mediators of Inflammation

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Background. Cerebral malaria (CM), a reversible encephalopathy affecting young children, is a medical emergency requiring rapid clinical assessment and treatment. However, understanding of the genes/proteins and the biological pathways involved in the disease outcome is still limited. Methods. We have performed a whole transcriptomic analysis of blood samples from Malian children with CM or uncomplicated malaria (UM). Hierarchical clustering and pathway, network, and upstream regulator analyses were performed to explore differentially expressed genes (DEGs). We validated gene expression for 8 genes using real-time quantitative PCR (RT-qPCR). Plasma levels were measured for IP-10/CXCL10 and IL-18. Results. A blood RNA signature including 538 DEGs (∣FC∣≥2.0, adjusted P value ≤ 0.01) allowed to discriminate between CM and UM. Ingenuity Pathway Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed novel genes and biological pathways related to immune/inflammatory responses, erythrocyte alteration, and neurodegenerative disorders. Gene expressions of CXCL10, IL12RB2, IL18BP, IL2RA, AXIN2, and NET were significantly lower in CM whereas ARG1 and SLC6A9 were higher in CM compared to UM. Plasma protein levels of IP-10/CXCL10 were significantly lower in CM than in UM while levels of IL-18 were higher. Interestingly, among children with CM, those who died from a complication of malaria tended to have higher concentrations of IP-10/CXCL10 and IFN-γ than those who recovered. Conclusions. This study identified some new factors and mechanisms that play crucial roles in CM and characterized their respective biological pathways as well as some upstream regulators.

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Section: Whole-transcriptome Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Understanding Human Cerebral Malaria through a Blood Transcriptomic Signature: Evidences for Erythrocyte Alteration, Immune/Inflammatory Dysregulation, and Brain Dysfunction

Cabantous

Poudiougou

Bergon

et al. 2020

Mediators of Inflammation

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“…The pathogenesis of the clinical and laboratory features of malaria is incompletely understood, and this is especially so for the progression from uncomplicated to severe malaria ( 13 ). Although transcriptomic approaches have the ability to broaden our understanding of the changes that occur in the host and the parasite during infection, relatively few studies have sought to associate gene expression with specific features of human disease ( 24 , 25 , 124 , 169 – 171 ). In contrast, transcriptomic studies with animal models have frequently been used to try to provide an understanding of the pathogenesis of severe malaria.…”

Section: Transcriptomic Studies Of Malariamentioning

confidence: 99%

“…Few studies have compared the human or mouse blood transcriptomes between CM and uncomplicated malaria ( 129 , 170 , 171 ) or between severe malaria phenotypes ( 187 ). In Malawian children initially treated for CM and subsequently reattending with an uncomplicated malaria episode, paired analyses of whole blood showed a striking upregulation of type I interferon-associated gene expression at presentation with uncomplicated malaria compared to the episode of severe malaria ( 129 ).…”

Section: Transcriptomic Studies Of Malariamentioning

confidence: 99%

“…However, changes in neutrophil gene expression signatures were not seen in ECM ( 173 ). A different perspective comes from a recent analysis of human PBMCs rather than whole blood, where comparison of genes associated with other neurodegenerative diseases between 7 children with CM and 8 with uncomplicated malaria suggested that protein aggregation pathways may be activated and important in CM ( 170 ).…”

Section: Transcriptomic Studies Of Malariamentioning

confidence: 99%

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Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions

Lee

Georgiadou

Otto

et al. 2018

Microbiol Mol Biol Rev

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SUMMARYTranscriptomics, the analysis of genome-wide RNA expression, is a common approach to investigate host and pathogen processes in infectious diseases. Technical and bioinformatic advances have permitted increasingly thorough analyses of the association of RNA expression with fundamental biology, immunity, pathogenesis, diagnosis, and prognosis. Transcriptomic approaches can now be used to realize a previously unattainable goal, the simultaneous study of RNA expression in host and pathogen, in order to better understand their interactions. This exciting prospect is not without challenges, especially as focus moves from interactions in vitro under tightly controlled conditions to tissue- and systems-level interactions in animal models and natural and experimental infections in humans. Here we review the contribution of transcriptomic studies to the understanding of malaria, a parasitic disease which has exerted a major influence on human evolution and continues to cause a huge global burden of disease. We consider malaria a paradigm for the transcriptomic assessment of systemic host-pathogen interactions in humans, because much of the direct host-pathogen interaction occurs within the blood, a readily sampled compartment of the body. We illustrate lessons learned from transcriptomic studies of malaria and how these lessons may guide studies of host-pathogen interactions in other infectious diseases. We propose that the potential of transcriptomic studies to improve the understanding of malaria as a disease remains partly untapped because of limitations in study design rather than as a consequence of technological constraints. Further advances will require the integration of transcriptomic data with analytical approaches from other scientific disciplines, including epidemiology and mathematical modeling.

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Systems Biology-Based Investigation of Host–Plasmodium Interactions

Smith

Styczynski

2018

Trends in Parasitology

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Malaria is a serious, complex disease caused by parasites of the genus Plasmodium. Plasmodium parasites affect multiple tissues as they evade immune responses, replicate, sexually reproduce, and transmit between vertebrate and invertebrate hosts. The explosion of omics technologies has enabled large-scale collection of Plasmodium infection data, revealing systems-scale patterns, mechanisms of pathogenesis, and the ways that host and pathogen affect each other. Here, we provide an overview of recent efforts using systems biology approaches to study host-Plasmodium interactions and the biological themes that have emerged from these efforts. We discuss some of the challenges in using systems biology for this goal, key research efforts needed to address those issues, and promising future malaria applications of systems biology.

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Gene Expression Analysis Reveals Genes Common to Cerebral Malaria and Neurodegenerative Disorders

Cited by 11 publications

References 16 publications

Understanding Human Cerebral Malaria through a Blood Transcriptomic Signature: Evidences for Erythrocyte Alteration, Immune/Inflammatory Dysregulation, and Brain Dysfunction

Understanding Human Cerebral Malaria through a Blood Transcriptomic Signature: Evidences for Erythrocyte Alteration, Immune/Inflammatory Dysregulation, and Brain Dysfunction

Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions

Systems Biology-Based Investigation of Host–Plasmodium Interactions

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