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Careful inspection of these genes reveals some that may have relevance to acute lymphoblastic leukemia, and so drugs for [http://gwilymgold.com/vanilla/discussion/1400557/discussion-the-epidermal-growth-factor-receptor-family-is-of-tremen-dous-biological-and-clinical-imp Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors] which these are targets provide potential can didates for repurposing. [http://www.health-style.ru/vanilla/discussion/2992/discussion-the-epidermal-growth-factor-receptor-family-is-of-tremen-dous-biological-and-clinical-imp Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors] FGFR1 is the drug target of Palifer min, a recombinant human keratinocyte growth factor for the treatment of oral mucositis associated with chemotherapy and radiation therapy. Its also the target for several experimental [http://gwilymgold.com/vanilla/discussion/1400535/discussion-the-epidermal-growth-factor-receptor-family-is-of-tremen-dous-biological-and-clinical-imp Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors] drugs. Thus, one of the high scoring ALL potential drug targets has now been approved for use for use with a new drug. Methods Connecting GWAS reported genes with drug targets using drug indication information from Drugbank GWAS reported genes The GWAS catalog was down loaded from. txt in January 2012. Non disease traits were removed by hand and multiple studies for each disease were com bined into unique sets. Reported genes were extracted to provide the list of GWAS genes for each disease. Drug targets Drugbank data were downloaded from in January 2012. Drugs for each disease in the GWAS list were identified by searching the indication information for all drugs in Drugbank. Then for each of these drugs, we extract all of the corresponding target genes. Verified drug targets Drug targets with the entry Pharmacological action labeled as Yes in the Drugbank. All 4013 GWAS reported genes and 1463 drug targets were mapped to NCBI gene IDs to provide unique identi fiers for comparison.  
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Characterization of the Pol IIII transcriptome in AC16 cells To further characterize the non Pol II transcriptome in AC16 cells, we mapped 739 non Pol II [http://www.jibwiskatsaca.org/discussion-forum/index.php?p=/discussion/101397/discussion-the-epidermal-growth-factor-receptor-family-is-of-tremen-dous-biological-and-clinical-imp Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors] transcripts from GRO seq data generated amanitin. This [http://amongthedead.com/atdtalk/index.php?p=/discussion/44040/discussion-the-epidermal-growth-factor-receptor-family-is-of-tremen-dous-biological-and-clinical-imp Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors] set of non Pol II transcripts includes mainly tRNAs, rRNAs, some snRNAs, and transcripts generated from SINE repeat elements, as well as 172 novel, previously unan notated transcripts. The lengths of the majority of the [http://sikap.purwakartakab.go.id/app/discussion/98732/discussion-the-epidermal-growth-factor-receptor-family-is-of-tremen-dous-biological-and-clinical-imp Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors] 739 primary non Pol II transcripts are 400 nucleotides, which indicates that they are short, non coding RNAs. The biological functions associated with the up and down regulated gene sets are closely related to cardiac function. For example motor protein and myosin related muscle functions are directly related to the elec trophysiology of heart muscle. fibroblast prolif eration and endothelial to mesenchymal transition contribute to cardiac fibrosis. and mitochon drial function and lipid oxidation are closely related to normal cardiac physiology. These dynamic transcriptome changes reflect the time dependent shift ing of biological processes in cardiomyocytes in re sponse to TNF. Interestingly, genes related to muscle function and inflammation are upregulated immediately, whereas genes related to mitochondrial function and metabolism are downregulated first and upregulated later in the time course. These results highlight the sequential transcriptional responses that underlie shifting cellular responses in cardiomyo cytes in response to TNF treatment. We augmented this analysis using a database from the Cardiovascular Gene Ontology Annotation Initiative project, which contains more than 4,278 genes critical for cardiac physiology and pathology. A large fraction of both up and downregulated genes are in the cardiac associated gene list and 20% are regulated by TNF treatment. Interestingly, 166 of the 1,146 enhancers predicted by GRO seq are located near genes critical for cardiac physiology. Collectively, our analyses of the TNF altered transcrip tome indicate that the AC16 cellular state switches from maintenance of basal housekeeping functions to defense against inflammatory stress. TNF induced transcriptome changes result in corresponding alterations in the steady state levels of mRNAs and proteins As expected, the TNF induced changes in the AC16 transcriptome result in corresponding changes in mature mRNA and protein levels in a similar manner, but with delayed kinetics. For example, the robust up regulated transcription of key TNF target genes is followed by corresponding changes in the steady state levels of the cognate mRNAs and proteins, with a delay of approxi mately 20 to 100 minutes for mRNA and 120 to 240 mi nutes for proteins. These results clearly illustrate how the dynamically regulated transcriptome alters the cellu lar proteome.  
  
For the 88 GWAS diseases with drugs in Drugbank, there are 1914 GWAS reported genes and 821 drug targets. The verified drug target set has 353 genes for 81 diseases. For each disease, we compare the list of GWAS reported genes and drug targets and find the overlap between these two lists. Calculating expected overlap between GWAS reported genes and drug targets using a random model We assume there are 20,000 human genes. For a specific disease, if there are m GWAS reported genes, and there are n drug targets for this disease the expected random overlap between the two gene lists for that disease is n m20000. We calculated the expected overlap for each disease and summed these to get the expected total number of overlaps between drug targets and GWAS reported genes for the same disease. SNP impact analysis for GWAS genes and drug target genes 1000 genomes VCF data were downloaded from The 2010 November data set is used. We extracted all non synonymous variants from 1000 genomes data based on Refseq annotation downloaded from the UCSC genome browser in Jan 2012, and calculated the allele frequency for each of the non reference variants by dividing the number of alleles by the number of total possible. We found non synonymous SNPs in the coding regions of 3550 out of the 4013 GWAS reported genes and 1249 out of the 1463 drug targets. The density of common non synonymous SNPs in each gene is calculated by dividing the number of non synon ymous SNPs with frequencies 5% for that gene by the length of that genes protein sequence provided by the UCSC genome browser.
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These results also further support our ob servation that AC16 cardiomyocytes secrete cytokines in response to TNF stimulation. These cyto kines may play an essential role in the overall effects of inflammation in cardiac biology. Role of non coding RNAs and the TNF induced proinflammatory transcriptome Protein coding genes represent only part of the AC16 transcriptome. the functions carried out by the non coding transcripts that we identified may also play critical roles in the inflammatory response in cardiomyocytes.

Version du 27 décembre 2015 à 19:33

Characterization of the Pol IIII transcriptome in AC16 cells To further characterize the non Pol II transcriptome in AC16 cells, we mapped 739 non Pol II Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors transcripts from GRO seq data generated amanitin. This Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors set of non Pol II transcripts includes mainly tRNAs, rRNAs, some snRNAs, and transcripts generated from SINE repeat elements, as well as 172 novel, previously unan notated transcripts. The lengths of the majority of the Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors 739 primary non Pol II transcripts are 400 nucleotides, which indicates that they are short, non coding RNAs. The biological functions associated with the up and down regulated gene sets are closely related to cardiac function. For example motor protein and myosin related muscle functions are directly related to the elec trophysiology of heart muscle. fibroblast prolif eration and endothelial to mesenchymal transition contribute to cardiac fibrosis. and mitochon drial function and lipid oxidation are closely related to normal cardiac physiology. These dynamic transcriptome changes reflect the time dependent shift ing of biological processes in cardiomyocytes in re sponse to TNF. Interestingly, genes related to muscle function and inflammation are upregulated immediately, whereas genes related to mitochondrial function and metabolism are downregulated first and upregulated later in the time course. These results highlight the sequential transcriptional responses that underlie shifting cellular responses in cardiomyo cytes in response to TNF treatment. We augmented this analysis using a database from the Cardiovascular Gene Ontology Annotation Initiative project, which contains more than 4,278 genes critical for cardiac physiology and pathology. A large fraction of both up and downregulated genes are in the cardiac associated gene list and 20% are regulated by TNF treatment. Interestingly, 166 of the 1,146 enhancers predicted by GRO seq are located near genes critical for cardiac physiology. Collectively, our analyses of the TNF altered transcrip tome indicate that the AC16 cellular state switches from maintenance of basal housekeeping functions to defense against inflammatory stress. TNF induced transcriptome changes result in corresponding alterations in the steady state levels of mRNAs and proteins As expected, the TNF induced changes in the AC16 transcriptome result in corresponding changes in mature mRNA and protein levels in a similar manner, but with delayed kinetics. For example, the robust up regulated transcription of key TNF target genes is followed by corresponding changes in the steady state levels of the cognate mRNAs and proteins, with a delay of approxi mately 20 to 100 minutes for mRNA and 120 to 240 mi nutes for proteins. These results clearly illustrate how the dynamically regulated transcriptome alters the cellu lar proteome.

These results also further support our ob servation that AC16 cardiomyocytes secrete cytokines in response to TNF stimulation. These cyto kines may play an essential role in the overall effects of inflammation in cardiac biology. Role of non coding RNAs and the TNF induced proinflammatory transcriptome Protein coding genes represent only part of the AC16 transcriptome. the functions carried out by the non coding transcripts that we identified may also play critical roles in the inflammatory response in cardiomyocytes.

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