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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human childrens host response to malaria

ABSTRACT: Subjects are children from Kilifi District Hospital, Kenya, recruited in 2001 malaria season. total RNA extracted from PaxGene tubes, total RNA and Stratagene Universal reference RNA underwent linear amplification (Message Amp, Ambion). Amplified RNA directly labelled Cy5 and Cy3 and hybridised to 'lymphochip' arrays (print run - lc36n). Scanned on Axon 4000B scanner using GenePix 4.0 software. Clinical sample ID provided in 'Disease State Description' corresponds with Sample ID in Table 1 "Clinical Information for the micro-array samples" in the associated publication.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Griffiths

PROVIDER: E-SMDB-2669 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genomewide analysis of the host response to malaria in Kenyan children.

Griffiths Michael J MJ Shafi Mohammed J MJ Popper Stephen J SJ Hemingway Cheryl A CA Kortok Moses M MM Wathen Andrew A Rockett Kirk A KA Mott Richard R Levin Michael M Newton Charles R CR Marsh Kevin K Relman David A DA Kwiatkowski Dominic P DP

The Journal of infectious diseases 20050414 10

Malaria is a global problem, and there is a critical need for further understanding of the disease process. When malarial parasites invade and develop within the bloodstream, they stimulate a profound host response whose main clinical sign is fever. To explore this response, we measured host gene expression in whole blood from Kenyan children hospitalized with either acute malaria or other febrile illnesses. Genomewide analysis of expression identified 2 principal gene-expression profiles relate ...[more]

PMID: 15838786

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Host Response Malaria

Project description:Subjects are children from Kilifi District Hospital, Kenya, recruited in 2001 malaria season. total RNA extracted from PaxGene tubes, total RNA and Stratagene Universal reference RNA underwent linear amplification (Message Amp, Ambion). Amplified RNA directly labelled Cy5 and Cy3 and hybridised to 'lymphochip' arrays (print run - lc36n). Scanned on Axon 4000B scanner using GenePix 4.0 software. Clinical sample ID provided in 'Disease State Description' corresponds with Sample ID in Table 1 "Clinical Information for the micro-array samples" in the associated publication. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design

2005-07-09 | GSE2900 | GEO

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Project description:Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. To identify determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing, we analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. We noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. We also observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. This suggests that differences in apoptotic and inflammatory gene expression patterns can predict susceptibility to clinical malaria.

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Environmental inhibition of RNA Pol III reduces malaria parasite virulence (during asymptomatic infection)

Project description:During the dry season, in many African regions, persistent asymptomatic malaria cases have been linked to downregulated virulence gene expression encoded by the var gene family, resulting in low adhesion and increased circulation time of Plasmodium falciparum-infected erythrocytes 1. Several studies have investigated associations between parasite transcription and clinical severity, but the underlying process that results in lower virulence gene expression in asymptomatic malaria remains unknown. Here we report an RNA Polymerase III-dependent mechanism that in response to external stimuli, decreases var gene transcription and parasite multiplication rate. The singular expression of var gene members, while under tight epigenetic regulation by the parasite 2, is additionally controlled by a family of ncRNA, termed RUF6 3. We show that Pol III transcription of tRNAs and RUF6 is severely decreased in field isolates of asymptomatic individuals infected with P. falciparum during the dry season. We identified Maf1 as a negative effector of RUF6 ncRNA transcription and show that external stimuli depend on plasmodial Maf1 to trigger lower expression of RNA Pol III-transcribed genes. Our results uncover a TOR-independent unprecedented signaling pathway in a protozoan pathogen that is highly relevant for establishing asymptomatic subclinical parasite persistence in the dry season.

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Transcription profiling of PfSPZ Malaria Vaccine trial subjects in a malaria endemic region

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Transcription profiling of PfSPZ Malaria Vaccine trial subjects receiving a 3-dose regimen in a malaria endemic region

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Genome wide transcriptional profiling of HIV positive and negative children with active tuberculosis, latent TB infection and other diseases from Kenya

Project description:The study aimed to define transcriptional signatures for detection of active TB (TB) compared to latent TB infection (LTBI) as well as to other diseases (OD) with similar clinical phenotypes in patients with and without HIV in a paediatric cohort from Kenya Transcriptional signatures were identified that distinguished active TB from LTBI, active TB from other diseases, and active TB from both LTBI and other diseases in HIV+/- patients. Children were recruited from 2 hospitals in Coast Province, Kenya (n=157) who were either HIV+ or HIV - with either active TB (culture confirmed), active TB (culture negative), LTBI or OD. Blood was collected into PAX gene tubes (PreAnalytiX). Total RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA). Labeled cRNA was hybridized to Illumina Human HT-12 Beadchips. Data were analysed in R.

2014-05-01 | E-GEOD-39939 | biostudies-arrayexpress

Transcription profiling by array of pyrethroid resistance in field populations of Anopheles funestus

Project description:Transcriptome profiling of pyrethroid resistant field populations of Anopheles funestus across Uganda and neighboring Kenya from Uganda and Kenya compared to a susceptible lab strain FANG

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Novel insights into the metabolic and biochemical underpinnings assisting dry-season survival in female malaria mosquitoes of the Anopheles gambiae complex

Project description:The mechanisms by which mosquitoes survive the desiccating conditions of the dry season in West African savannahs and are able to readily transmit malaria as soon as the rains start remain largely unknown. Thus, we examined the degree to which the physiology of 1 h- and 24 h-old female An. gambiae M and S is altered at the onset of the dry season (“ods”) by examining their metabolic fingerprints and protein expression, which were compared to those of females exposed to the rainy season (“rs”) conditions. Three amino acids (phenylalanine, tyrosine and valine) that play a pivotal role in cuticle hardness were significantly decreased from the 1 h- to 24 h-old females, regardless of the experimental conditions. These amino acids were present in higher amounts in 1 h-old female An. gambiae M reared under “ods”; such a seasonal difference was not reported in the female S molecular form. Together with the increased expression of cuticular proteins 70 and 117(spots 67 and 65, respectively), our data suggest that the cuticle thickness, rigidity and permeability were adjusted at the onset of the dry season. Evident signs of energetic metabolism adjustments were found in both of the molecular forms at the onset of the dry season. Moreover, 1 h-old females of An. gambiae S were characterised by elevated amounts of glycogen phosphorylase, isocitrate dehydrogenase and citrate synthase, suggesting an increase of their metabolic activity at the onset of the dry season. This study presents novel insights into drought resistance in the mosquitoes of utmost medical importance.

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Long non-coding RNAs detected in Plasmodium falciparum malaria using high-resolution DNA tiling microarray technology.

Project description:Survey of transcriptional activity across 22.6% of the P. falciparum strain 3D7 genome. 872 protein coding genes and 60 putative P. falciparum lncRNAs identified under developmental regulation during the parasite's pathogenic human blood stage. Total RNA was isolated from synchronous in vitro parasite cultures at 18, 24, 30, and 36 hours post invasion (hpi) of red blood cells. 1 μg of total RNA was then subjected to poly-A selective amplification using Message Amp II (Ambion), substituting biased dNTP/NTP mixes (2A/T/U:1C/G). The resulting aRNA was labeled with Superscript II reverse transcriptase (Invitrogen), using random hexamers, and either Cy3- or Cy5-dUTPs (Amersham).

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