Histone modifications are a key epigenetic mechanism to activate or repress the expression of genes. Data sets of matched microarray expression data and histone modification data measured by ChIP-seq exist, but methods for integrative analysis of both data types are still rare. Here, we present a novel bioinformatic approach to detect genes that are differentially expressed between two conditions putatively caused by alterations in histone modification. We introduce a correlation measure for integrative analysis of ChIP-seq and gene expression data and demonstrate that a proper normalization of the ChIP-seq data is crucial. We suggest applying Bayesian mixture models of different distributions to further study the distribution of the correlation measure. The implicit classification of the mixture models is used to detect genes with differences between two conditions in both gene expression and histone modification. The method is applied to different data sets and its superiority to a naive separate analysis of both data types is demonstrated. This GEO series contains the expression data of the Cebpa example data set.
Integrative analysis of histone ChIP-seq and transcription data using Bayesian mixture models.
No sample metadata fields
View SamplesAcute myeloid leukemia (AML) is a heterogeneous disease and AML with normal karyotype (AML-NK) is categorized as an intermediate-risk group. Over the past years molecular analyses successfully identified biomarkers that will further allow to dissecting clinically meaningful subgroups in this disease. Thus far, somatic mutations were identified which elucidate the disturbance of cellular growth, proliferation, and differentiation processes in hematopoietic progenitor cells. In AML-NK, acquired gene mutations with prognostic relevance were identified for FLT3, CEBPA, and NPM1. FLT3-ITD mutations were associated with short relapse-free and overall survival, while mutations in CEBPA or NPM1 (without concomitant FLT3-ITD) had a more favorable outcome.
Quantitative comparison of microarray experiments with published leukemia related gene expression signatures.
Sex, Age, Disease, Disease stage
View SamplesFull Title: Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: A comparison of 408 cases classified as AML not otherwise specified or AML with myelodysplasia-related changes
Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as "AML not otherwise specified" (AML-NOS) or "AML with myelodysplasia-related changes" (AML-MRC).
No sample metadata fields
View SamplesInterest focuses on genes encoding histone demethylases in hematologic malignancies, such as EZH2 (enhancer of zeste homolog 2). EZH2 mutations were recurrently observed in lymphomas and chronic myeloid malignancies, but data in acute leukemias are limited. We investigated 13 PICALM-MLLT10 (=CALM-AF10) rearranged acute leukemia predominantly of T-lineage (7 m/6 f; 653 years) by deep-sequencing for EZH2mut and identified 3 (23%) EZH2mut carriers: one splice site mutation in exon 14, while two patients had missense mutations in the D1 region of exon 5 which interacts with different DNA methyltransferase genes (but no DNMT3Amut was detected in the 13 PICALM-MLLT10-positive patients).
EZH2 mutations and their association with PICALM-MLLT10 positive acute leukaemia.
Specimen part, Disease, Disease stage
View SamplesGSE2240 contains two different experimental subsets:
Functional profiling of human atrial and ventricular gene expression.
No sample metadata fields
View SamplesCancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. Here, we analyzed genome wide DNA methylation changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer with Reduced Representation Bisulfite Sequencing. DNMT-inhibition by 5-Azacytidine at low concentrations reverted the pro-metastatic phenotype. 5-Azacytidine led to preferential loss of DNA methylation at sites that were DNA hypermethylated during the in vivo selection. Changes in DNA methylation persisted over time.
DNA methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting polycomb target genes.
Cell line
View SamplesHere, we analyzed global gene expression changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer using the Affymetrix microarray platform.
DNA methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting polycomb target genes.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Increased DNA methylation of Dnmt3b targets impairs leukemogenesis.
Specimen part
View SamplesHere, we analyzed global gene expression changes that were associated with over expression of Dnmt3b in MLL-AF9 induced leukemias using the Affymetrix microarray platform.
Increased DNA methylation of Dnmt3b targets impairs leukemogenesis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia.
Cell line, Treatment
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