The frequency of druggable targets in localized prostate cancer: Initial analysis from the Decipher GRID.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 98-98
Author(s):  
Nicholas Erho ◽  
Mohammed Alshalalfa ◽  
Penelope J. Wood ◽  
Mandeep Takhar ◽  
Hussam Al-Deen Ashab ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Clinical Relevance ◽  
Expression Patterns ◽  
High Expression ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Resource ◽  
Druggable Targets ◽  
Low Expression

98 Background: Prostate cancers patient management has been enhanced with commercially available genomic prognostic tests such as the Decipher prostate cancer classifier that are useful for making treatment decision-making. In addition to being the most validated predictor of metastasis in prostate cancer, Decipher is also a genome-wide assay that measures the expression of many druggable targets. Methods: Decipher GRID (Genomic Resource Information Database), was queried to assess the expression patterns of 14 genes from 5 biological pathways (Table) in 1,850 patients from previously published Decipher validation studies. The frequency of high (or low) expression of each gene was ascertained using a standard and more conservative thresholds based on the median absolute deviation (MAD) metric. For the standard threshold, genes whose high expression is of clinical relevance, patients with gene expression above the median + 1.48*MAD were annotated as high expression and for genes whose low expression is of clinical relevance, patients with gene expression below the median - 1.48*MAD were annotated as low expression. For the conservative threshold, median +/- 2*1.48*MAD was used. Results: See Table. Conclusions: Since every patient receiving the Decipher test also has a genome-wide expression profile, the Decipher GRID will allow researchers to evaluate on a systematic population-level the expression of genes that may be targeted with existing therapies. Such information may be useful for selection of optimal systemic therapy and inclusion into clinical trials of novel targeted agents. This rich genomic resource is being made available on a research use only basis to prostate cancer researchers and to clinicians seeking to uncover individualized genomic insights for patients to advance precision medicine. [Table: see text]

scholarly journals DNA hypermethylation associated with upregulated gene expression in prostate cancer demonstrates the diversity of epigenetic regulation

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ieva Rauluseviciute ◽  
Finn Drabløs ◽  
Morten Beck Rye
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Normal Tissue ◽  
Expression Profiles ◽  
Expression Data ◽  
Dna Hypermethylation ◽  
Genome Wide ◽  
A Genome

Abstract Background Prostate cancer (PCa) has the highest incidence rates of cancers in men in western countries. Unlike several other types of cancer, PCa has few genetic drivers, which has led researchers to look for additional epigenetic and transcriptomic contributors to PCa development and progression. Especially datasets on DNA methylation, the most commonly studied epigenetic marker, have recently been measured and analysed in several PCa patient cohorts. DNA methylation is most commonly associated with downregulation of gene expression. However, positive associations of DNA methylation to gene expression have also been reported, suggesting a more diverse mechanism of epigenetic regulation. Such additional complexity could have important implications for understanding prostate cancer development but has not been studied at a genome-wide scale. Results In this study, we have compared three sets of genome-wide single-site DNA methylation data from 870 PCa and normal tissue samples with multi-cohort gene expression data from 1117 samples, including 532 samples where DNA methylation and gene expression have been measured on the exact same samples. Genes were classified according to their corresponding methylation and expression profiles. A large group of hypermethylated genes was robustly associated with increased gene expression (UPUP group) in all three methylation datasets. These genes demonstrated distinct patterns of correlation between DNA methylation and gene expression compared to the genes showing the canonical negative association between methylation and expression (UPDOWN group). This indicates a more diversified role of DNA methylation in regulating gene expression than previously appreciated. Moreover, UPUP and UPDOWN genes were associated with different compartments — UPUP genes were related to the structures in nucleus, while UPDOWN genes were linked to extracellular features. Conclusion We identified a robust association between hypermethylation and upregulation of gene expression when comparing samples from prostate cancer and normal tissue. These results challenge the classical view where DNA methylation is always associated with suppression of gene expression, which underlines the importance of considering corresponding expression data when assessing the downstream regulatory effect of DNA methylation.

scholarly journals The Potential Role of Genetic Assimilation during Maize Domestication

2017 ◽  
Author(s):  
Anne Lorant ◽  
Sarah Pedersen ◽  
Irene Holst ◽  
Matthew B. Hufford ◽  
Klaus Winter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zea Mays ◽  
Potential Role ◽  
Expression Patterns ◽  
Genetic Assimilation ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Mechanisms ◽  
Maize Domestication

ABSTRACTDomestication research has largely focused on identification of morphological and genetic differences between extant populations of crops and their wild relatives. Little attention has been paid to the potential effects of environment despite substantial known changes in climate from the time of domestication to modern day. Recent research, in which maize and teosinte (i.e., wild maize) were exposed to environments similar to the time of domestication, resulted in a plastic induction of domesticated phenotypes in teosinte and little response to environment in maize. These results suggest that early agriculturalists may have selected for genetic mechanisms that cemented domestication phenotypes initially induced by a plastic response of teosinte to environment, a process known as genetic assimilation. To better understand this phenomenon and the potential role of environment in maize domestication, we examined differential gene expression in maize (Zea mays ssp. mays) and teosinte (Zea mays ssp. parviglumis) between past and present conditions. We identified a gene set of over 2000 loci showing a change in expression across environmental conditions in teosinte and invariance in maize. In fact, overall we observed both greater plasticity in gene expression and more substantial re-wiring of expression networks in teosinte across environments when compared to maize. While these results suggest genetic assimilation played at least some role in domestication, genes showing expression patterns consistent with assimilation are not significantly enriched for previously identified domestication candidates, indicating assimilation did not have a genome-wide effect.

scholarly journals Genome-Wide Phylogenetic Analysis, Expression Pattern, and Transcriptional Regulatory Network of the Pig C/EBP Gene Family

2021 ◽  
Vol 17 ◽  
pp. 117693432110413
Author(s):  
Chaoxin Zhang ◽  
Tao Wang ◽  
Tongyan Cui ◽  
Shengwei Liu ◽  
Bing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phylogenetic Analysis ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Genome Wide ◽  
A Genome

The CCAAT/enhancer binding protein (C/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification revealed the presence of a total of 99 C/EBP genes in pig and 19 eukaryote genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into 6 subgroups named C/EBPα, C/EBPβ, C/EBPδ, C/EBPε, C/EBPγ, and C/EBPζ. Gene expression analysis showed that the C/EBPα, C/EBPβ, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various pig tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs and miRNAs. A total of 27 feed-forward loop (FFL) motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to FFL sub-network were analyzed in 27 adult pig tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

scholarly journals A genome-wide transcriptional analysis of morphology determination inCandida albicans

2013 ◽  
Vol 24 (3) ◽  
pp. 246-260 ◽  
Author(s):  
Patricia L. Carlisle ◽  
David Kadosh
Keyword(s):  
Gene Expression ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Transcriptional Analysis ◽  
Specific Gene ◽  
Genome Wide ◽  
A Genome ◽  
Genetically Manipulated

Candida albicans, the most common cause of human fungal infections, undergoes a reversible morphological transition from yeast to pseudohyphal and hyphal filaments, which is required for virulence. For many years, the relationship among global gene expression patterns associated with determination of specific C. albicans morphologies has remained obscure. Using a strain that can be genetically manipulated to sequentially transition from yeast to pseudohyphae to hyphae in the absence of complex environmental cues and upstream signaling pathways, we demonstrate by whole-genome transcriptional profiling that genes associated with pseudohyphae represent a subset of those associated with hyphae and are generally expressed at lower levels. Our results also strongly suggest that in addition to dosage, extended duration of filament-specific gene expression is sufficient to drive the C. albicans yeast-pseudohyphal-hyphal transition. Finally, we describe the first transcriptional profile of the C. albicans reverse hyphal-pseudohyphal-yeast transition and demonstrate that this transition involves not only down-regulation of known hyphal-specific, genes but also differential expression of additional genes that have not previously been associated with the forward transition, including many involved in protein synthesis. These findings provide new insight into genome-wide expression patterns important for determining fungal morphology and suggest that in addition to similarities, there are also fundamental differences in global gene expression as pathogenic filamentous fungi undergo forward and reverse morphological transitions.

scholarly journals Genome-wide transcriptional profiling uncovers a similar oligodendrocyte-related transcriptional response to acute and chronic alcohol drinking in the amygdala

2021 ◽  
Author(s):  
Sharvari Narendra ◽  
Claudia Klengel ◽  
Bilal Hamzeh ◽  
Drasti Patel ◽  
Joy Otten ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alcohol Drinking ◽  
Brain Area ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Histone Deacetylation ◽  
Regulatory Pathways ◽  
Genome Wide ◽  
A Genome

AbstractAlcohol intake progressively increases after prolonged consumption of alcohol, but relatively few new therapeutics targeting development of alcohol use disorder (AUD) have been validated. Here, we conducted a genome-wide RNA-sequencing (RNA-seq) analysis in mice exposed to different modes (acute vs chronic) of ethanol drinking. We focused on transcriptional profiles in the amygdala including the central and basolateral subnuclei, a brain area previously implicated in alcohol drinking and seeking, demonstrating distinct gene expression patterns and canonical pathways induced by both acute and chronic intake. Surprisingly, both drinking modes triggered similar transcriptional changes, including up-regulation of ribosome-related/translational pathways and myelination pathways, and down-regulation of chromatin binding and histone modification. Notably, multiple genes that were significantly regulated in mouse amygdala with alcohol drinking, including Atp2b1, Slc4a7, Nfkb1, Nts, and Hdac2, among others had previously been associated with human AUD via GWAS or other genomic studies. In addition, analyses of hub genes and upstream regulatory pathways predicted that voluntary ethanol consumption affects epigenetic changes via histone deacetylation pathways, oligodendrocyte and myelin function, and oligodendrocyte-related transcriptional factor, Sox17.Overall, our results suggest that the transcriptional landscape in the central and basolateral subnuclei of the amygdala is sensitive to voluntary alcohol drinking. They provide a unique resource of gene expression data for future translational studies examining transcriptional mechanisms underlying the development of AUD due to alcohol consumption.

scholarly journals H3K4me3 is neither instructive for, nor informed by, transcription

2019 ◽  
Author(s):  
Struan C Murray ◽  
Philipp Lorenz ◽  
Françoise S Howe ◽  
Meredith Wouters ◽  
Thomas Brown ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Environmental Changes ◽  
Expression Patterns ◽  
Gene Activity ◽  
Protein Levels ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Cell Variation

AbstractH3K4me3 is a near-universal histone modification found predominantly at the 5’ region of genes, with a well-documented association with gene activity. H3K4me3 has been ascribed roles as both an instructor of gene expression and also a downstream consequence of expression, yet neither has been convincingly proven on a genome-wide scale. Here we test these relationships using a combination of bioinformatics, modelling and experimental data from budding yeast in which the levels of H3K4me3 have been massively ablated. We find that loss of H3K4me3 has no effect on the levels of nascent transcription or transcript in the population. Moreover, we observe no change in the rates of transcription initiation, elongation, mRNA export or turnover, or in protein levels, or cell-to-cell variation of mRNA. Loss of H3K4me3 also has no effect on the large changes in gene expression patterns that follow galactose induction. Conversely, loss of RNA polymerase from the nucleus has no effect on the pattern of H3K4me3 deposition and little effect on its levels, despite much larger changes to other chromatin features. Furthermore, large genome-wide changes in transcription, both in response to environmental stress and during metabolic cycling, are not accompanied by corresponding changes in H3K4me3. Thus, despite the correlation between H3K4me3 and gene activity, neither appear to be necessary to maintain levels of the other, nor to influence their changes in response to environmental stimuli. When we compare gene classes with very different levels of H3K4me3 but highly similar transcription levels we find that H3K4me3-marked genes are those whose expression is unresponsive to environmental changes, and that their histones are less acetylated and dynamically turned-over. Constitutive genes are generally well-expressed, which may alone explain the correlation between H3K4me3 and gene expression, while the biological role of H3K4me3 may have more to do with this distinction in gene class.

scholarly journals Genome-Wide Analysis of Dof Genes and Their Response to Abiotic Stress in Rose (Rosa chinensis)

2021 ◽  
Vol 12 ◽  
Author(s):  
Hong Nan ◽  
Richard A. Ludlow ◽  
Min Lu ◽  
Huaming An
Keyword(s):  
Gene Expression ◽  
Abiotic Stress ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Functional Characterization ◽  
Stress Conditions ◽  
Genome Wide Analysis ◽  
Rosa Chinensis ◽  
Genome Wide ◽  
A Genome

Dof (DNA binding with one finger) proteins play important roles in plant development and defense regulatory networks. In the present study, we report a genome-wide analysis of rose Dof genes (RchDof), including phylogenetic inferences, gene structures, chromosomal locations, gene duplications, and expression diversity. A total of 24 full-length RchDof genes were identified in Rosa chinensis, which were assigned to nine distinct subgroups. These RchDof genes were unevenly distributed on rose chromosomes. The genome-scale analysis of synteny indicated that segmental duplication events may have played a major role in the evolution of the RchDof gene family. Analysis of cis-acting elements revealed putative functions of Dofs in rose during development as well as under numerous biotic and abiotic stress conditions. Moreover, the expression profiles derived from qRT-PCR experiments demonstrated distinct expression patterns in various tissues, and gene expression divergence existed among the duplicated RchDof genes, suggesting a fundamentally functional divergence of the duplicated Dof paralogs in rose. The gene expression analysis of RchDofs under drought and salt stress conditions was also performed. The present study offered novel insights into the evolution of RchDofs and can aid in the further functional characterization of its candidate genes.

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