Gene expression of SLNs (Synthetic Lethal with Nutlin-3) on HCT116 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jihye Kim
PROVIDER: E-GEOD-36593 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Nr4a1 deficient rats (Nr4a1-/-) were developed using the fawn hooded hypertensive rat (FHH), which provided a genetic background susceptible to kidney injury. Both groups of animals were evaluated for blood pressure, proteinuria, renal function, and whole transcriptome gene pathway changes. Gene expression profiling was performed at week 8, 16, and 24 using kidney from FHH and Nr4a1-/- rats. To identify differentially expressed gene between FHH and Nr4a1-/- two statistical methods were utilized: (1) FWER (family-wise error rate) procedure, p<0.05 and fold-change M-BM-11.2 or greater; and/or (2) Benjamani and Hochberg FDR (false discovery rate) using p<0.05, and fold-change M-BM-11.2 or greater. Two-way ANOVA using a p<0.01 or lower was performed to identify strain X time interaction effects between groups. Gene networks and functional analysis were evaluated through the use of Ingenuity Pathways Analysis . FHH and Nr4a1-/- rats were grown to 8, 16, and 24 weeks of age and kidney tissue was harvested for transcriptome analysis (n=3 replicates/ per group/ time)
2014-02-06 | E-GEOD-54714 | biostudies-arrayexpress
Project description:While blood transcriptional profiling has improved diagnosis and understanding of disease pathogenesis of adult tuberculosis (TB), no studies applying gene expression profiling of children with TB have been described so far. In this study, we have compared whole blood gene expression in childhood TB patients, as well as in healthy latently infected (LTBI) and uninfected (HC) children in a cohort of Warao Amerindians in the Delta Amacuro in Venezuela. We identified a 116-gene signature set by means of random forest analysis that showed an average prediction error of 11% for TB vs. LTBI and for TB vs. LTBI vs. HC in our dataset. Furthermore, a minimal set of only 9 genes showed a significant predictive value for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. 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We conclude that our data justify the further exploration of our signature set as biomarkers to diagnose childhood TB. Furthermore, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts. In this study, 27 children 1 to 15 years of age with TB (n=9), LTBI (n=9) and HC (n=9) were recruited between May 2010 and December 2010. Tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assay (QFT-GIT) were performed on all children. A sputum sample was collected from all children with expectoration and a gastric aspirate was taken from all children under 6 years of age. Children with active TB were diagnosed based on culture of M. tuberculosis (n=2) or on the basis of clinical, epidemiological and radiological features (n=7). The latter group were children with a TST = 10 mm or a positive QFT-GIT result who presented all of: persistent fever >38M-BM-0C objectively recorded daily for at least two weeks, persistent cough for more than three weeks, weight loss (>5% reduction in weight compared with the highest weight recorded in last three months) or failure to thrive (documented crossing of percentile lines in the preceding three months), persistent lethargy or decrease in playfulness/activity reported by the parent and absence of clinical response on broad-spectrum antibiotics. Standard antero-posterior and lateral chest radiographs (CXRs) were taken from all children. Two independent experts, blinded to all clinical information, evaluated the CXRs and documented their findings on a standard report form. Where the two objective experts disagreed, a third expert was consulted and final consensus was achieved. 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