This SuperSeries is composed of the SubSeries listed below.
Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination.
Disease, Disease stage
View SamplesPatients with oncogene driven tumors are currently treated with targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors. The inhibited oncogenic pathway often interacts with other signaling pathways and alters predicted therapeutic response. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates pervasive molecular alterations to EGFR, MAPK, and PI3K signaling in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to infer the complex pathway interactions that result from EGFR inhibitor use in cancer cells that contain these these common EGFR network genetic alterations. To do this, we modified the HaCaT keratinocyte cell line model of premalignancy to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background. We then measured gene expression after treating modified HaCaT cells with three EGFR targeted agents (gefitinib, afatinib, and cetuximab) for 24 hours.
CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.
Cell line, Treatment
View SamplesTo determine the expression AP2-alpha target genes, global gene expression of 7 HNSCC cell lines with and without cetuximab treatment (100 nM, 24 hrs) and the HaCaT keratinocyte cell line was performed.
CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.
Specimen part, Cell line
View SamplesThis study integrated Affymetrix SNPchip data for CNV estimation, Affymetrix HuEx1.0 data for gene expression estimation, and Illumina HumanMethylation27k BeadChip data for promoter methylation to estimate pathway activity
Activation of the NOTCH pathway in head and neck cancer.
Disease, Disease stage
View SamplesStudies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders.
Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesPolycomb repressive complex 2 (PRC2) catalyzes histone H3K27me3, which characterizes many silenced genes including those on the inactive X-chromosome. Here we interrogate the role of core PRC2 protein EED in X-linked gene silencing by assessing allele-specific X-linked gene expression in WT and Eed-/- hybrid mouse trophoblast stem cells (TSCs) harboring a 129/S1-derived maternal X-chromosome and a JF1/Ms-derived paternal X-chromosome. This study generates mRNA-seq data for WT and Eed-/- TSCs, which undergo imprinted inactivation of the paternal X-chromosome. RNA-seq data was mapped allele-specifically to in silico strain-specific maternal and paternal reference genomes, generated based on known single nucleotide polymorphisms. We find that EED loss abrogates H3K27me3 and expression of Xist lncRNA, which is required for X-inactivation, however, despite the absence of H3K27me3 and Xist, only a subset of PRC2 target genes are derepressed in Eed-/- TSCs. Overall design: RNA-seq profiles of four WT (Eed +/+ and Eed fl/fl) and three EED null (Eed -/-) female TS cell lines were generated through strand-specific 100 bp paired-end sequencing on the Illumina HiSeq2000
PRC2 represses transcribed genes on the imprinted inactive X chromosome in mice.
Specimen part, Subject
View SamplesThe objective of the experiment is to determine the genes differentially expressed in the liver of the chromogranin A knockout mouse (Mahapatra et al., 2005).
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesThe objective of the experiment is to determine the genes differentially expressed in the adrenal gland of the chromogranin A knockout mouse (Mahapatra et al., 2005).
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesTBX5 is hypomethylated in Rheumatoid Arthritis synovial fibroblasts (RASF). Hypomethylation increased the TBX5 expression in RASF.
Epigenome analysis reveals TBX5 as a novel transcription factor involved in the activation of rheumatoid arthritis synovial fibroblasts.
Specimen part
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