Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29333 | GEO | 2012/01/01
SECONDARY ACCESSION(S): PRJNA140133
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE29312: Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1) - train set GSE29332: Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1) - test set Refer to individual Series
2012-01-01 | E-GEOD-29333 | biostudies-arrayexpress
Project description:Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In this study we tested the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. Here, we compare unstimulated whole blood gene expression profiles of 20 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 9 uninfected healthy control subjects to (1) identify a transcriptional signature associated with presence of HAM and (2) identify cell types and pathways abnormally regulated in HAM by canonical and modular pathway analysis.
2012-01-01 | GSE29312 | GEO
Project description:Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In a previous study we identified a 80-gene transcriptional signature of HAM based in the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. In this study we wished to validate the 80-gene signature on an independent cohort comprising 17 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 8 uninfected healthy control subjects.
2012-01-01 | GSE29332 | GEO
Project description:Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In a previous study we identified a 80-gene transcriptional signature of HAM based in the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. In this study we wished to validate the 80-gene signature on an independent cohort comprising 17 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 8 uninfected healthy control subjects. Patients attending the HTLV-1 clinic at St Mary’s hospital in London, UK were classified according to their clinical status as asymptomatic HTLV-1 carriers (ACs, n=17), patients with HTLV-1-associated meylopathy (HAM, n=10) or uninfected control subjects (n=8). Three ml of blood were drawn into a Tempus tube (Applied Biosystems, Foster City, CA, USA). Total RNA was extracted, globin mRNA depleted and following cRNA generation samples were analysed on HUmanWG6 v3 Illumina BeadChip arrays.
2012-01-01 | E-GEOD-29332 | biostudies-arrayexpress
Project description:Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In this study we tested the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. Here, we compare unstimulated whole blood gene expression profiles of 20 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 9 uninfected healthy control subjects to (1) identify a transcriptional signature associated with presence of HAM and (2) identify cell types and pathways abnormally regulated in HAM by canonical and modular pathway analysis. Patients attending the HTLV-1 clinic at St Mary’s hospital in London, UK were classified according to their clinical status as asymptomatic HTLV-1 carriers (ACs, n=20), patients with HTLV-1-associated meylopathy (HAM, n=10) or uninfected control subjects (n=9). HTLV-1 proviral load (PVL) can differ among individuals by more than 10-fold and is typically higher in patients with HAM than in ACs, with a 1% PVL cut off generally separating disease from asymptomatic carriage. Thus, ACs were subdivided into AC low PVL (<1% infected PBMCs) and AC high PVL (>1% infected PBMCs). Three ml of blood were drawn into a Tempus tube (Applied Biosystems, Foster City, CA, USA). Total RNA was extracted, globin mRNA depleted and following cRNA generation samples were analysed on HUmanHT12 v3 Illumina BeadChip arrays.
2012-01-01 | E-GEOD-29312 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-11-30 | GSE74591 | GEO
Project description:BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) is the agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), observed in up to 5% of infected individuals. Despite low prevalence, many HTLV-1-infected patients who do not fulfill criteria for HAM/TSP present with neurological complaints related to sensory, motor, urinary, or autonomic manifestations. The aim of this study was to determine the incidence of neurologic manifestations and risk factors associated with these outcomes.MethodsThe incidence of HAM/TSP and new signs and neurologic symptoms were computed in a group of patients enrolled in a cohort study.ResultsOf 414 subjects, 76 had definite HAM/TSP, 87 had possible or probable HAM/TSP, and 251 subjects had no neurologic manifestation and were selected for analysis. Definite HAM/TSP developed in 5 (1.47%) patients. Follow-up of at least 3 years was achieved in 51% of patients. The incidence rate was computed in 1000 person-years (206 for hand numbness, 187 for feet numbness, 130 for nocturia, and 127 for urgency). Average incidence rate in neurological exam was 76 for leg hyperreflexia, 53 for leg weakness, and 37 for Babinski sign. In the applied Expanded Disability Status Scale, the incidence rate of worsening 1 point was 134 per 1000 person-years. Kaplan-Meier curves stratified by sex and proviral load showed that females and patients with proviral load >50,000 copies/10(6) peripheral blood mononuclear cells had a higher risk of progression.ConclusionsDevelopment of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up.
| S-EPMC4542911 | biostudies-literature
Project description:BackgroundHuman T-lymphotropic virus (HTLV) type I is the causative agent of HTLV-associated myelopathy (HAM)/tropical spastic paraparesis, and a number of HAM cases with HTLV-II infection have also been reported. However, despite some reports, it is unclear whether HTLV-I or -II infection is associated with other neurologic manifestations.MethodsAn analysis of medical histories and screening neurologic examinations from a prospective cohort of 153 HTLV-I, 388 HTLV-II, and 810 HTLV-seronegative individuals followed up for means of 11.5, 12.0, and 12.2 years was performed. Participants diagnosed with HAM were excluded. We calculated odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, race or ethnicity, income, educational attainment, body mass index, alcohol and cigarette consumption, injection drug use, diabetes, and hepatitis C virus status, using generalized estimating equations for repeated measures.ResultsHTLV-I and -II participants were more likely than seronegative participants to have leg weakness (ORs 1.67 [95% CI 1.28-2.18] and 1.44 [1.16-1.78]), impaired tandem gait (ORs 1.25 [95% CI 1.07-1.47] and 1.45 [1.27-1.64]), Babinski sign (ORs 1.54 [95% CI 1.13-2.08] and 1.51 [1.18-1.93]), impaired vibration sense (ORs 1.16 [95% CI 1.01-1.33] and 1.27 [1.14-1.42]), and urinary incontinence (ORs 1.45 [95% CI 1.23-1.72] and 1.70 [1.50-1.93]). For both HTLV-I and -II participants, higher odds of sensory neuropathy by monofilament examination were no longer significant after adjustment for confounding.ConclusionsThese results provide strong evidence that human T-lymphotropic virus (HTLV)-I and -II are associated with a spectrum of predominantly motor abnormalities in patients without overt HTLV-associated myelopathy. Further investigation of the clinical course and etiology of these abnormalities is warranted.
| S-EPMC2739606 | biostudies-literature
Project description:Although the analysis of linkage disequilibrium (LD) plays a central role in many areas of population genetics, the sampling variance of LD is known to be very large with high sensitivity to numbers of nucleotide sites and individuals sampled. Here we show that a genome-wide analysis of the distribution of heterozygous sites within a single diploid genome can yield highly informative patterns of LD as a function of physical distance. The proposed statistic, the correlation of zygosity, is closely related to the conventional population-level measure of LD, but is agnostic with respect to allele frequencies and hence likely less prone to outlier artifacts. Application of the method to several vertebrate species leads to the conclusion that >80% of recombination events are typically resolved by gene-conversion-like processes unaccompanied by crossovers, with the average lengths of conversion patches being on the order of one to several kilobases in length. Thus, contrary to common assumptions, the recombination rate between sites does not scale linearly with distance, often even up to distances of 100 kb. In addition, the amount of LD between sites separated by <200 bp is uniformly much greater than can be explained by the conventional neutral model, possibly because of the nonindependent origin of mutations within this spatial scale. These results raise questions about the application of conventional population-genetic interpretations to LD on short spatial scales and also about the use of spatial patterns of LD to infer demographic histories.
| S-EPMC4174938 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-01 | E-GEOD-59843 | biostudies-arrayexpress