Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistance of HIV to antiretroviral drugs was studied in 210 samples taken in the last two years from patients at the Molecular Biology Unit of the Microbiology Department of the Hospital La Fe in Valencia, Spain. Once the viral load in plasma was determined, resistance was detected using complete gene sequencing for protease until position 3464 of the HIV-1 inverse transcriptase gene. The results were analyzed using the programs Omiga 1.2 (Oxford Molecular Group) and HR-ASAP 1.0 (Stanford University). The protease inhibitors the least affected by the presence of mutations leading to resistance were amprenavir (68.96% activity), and lopinavir (70.69% activity), and of the inverse transcriptase inhibitors, tenofovir (94.02% activity), D4T (74.62% activity) and 3TC (76.12% activity). The treatment combination with the greatest activity, based on the different mutations, was D4T + 3TC + NNRTI. To justify the persistence of viremia with relatively low genotypic resistance to antiretroviral drugs other variables must be considered, such as treatment compliance and the pharmacokinetics of the drugs.
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PMID:[Resistance of HIV-1 to antiretroviral drugs in Valencia (Spain): mutations and susceptibility]. 1470 23

Alternative splicing has recently emerged as a major mechanism of regulation in the human genome, occurring in perhaps 40-60% of human genes. Thus, microarray studies of functional regulation could, in principle, be extended to detect not only the changes in the overall expression of a gene, but also changes in its splicing pattern between different tissues. However, since changes in the total expression of a gene and changes in its alternative splicing can be mixed in complex ways among a set of samples, separating these effects can be difficult, and is essential for their accurate assessment. We present a simple and general approach for distinguishing changes in alternative splicing from changes in expression, based on detecting systematic anti-correlation between the log-ratios of two different samples versus a pool containing both samples. We have tested this analysis method on microarray data for five human tissues, generated using a standard microarray platform and experimental protocols shown previously to be sensitive to alternative splicing. Our automatic analysis was able to detect a wide variety of tissue-specific alternative splicing events, such as exon skipping,mutually exclusive exons, alternative 3' and alternative 5' splicing, alternative initiation and alternative termination, all of which were validated by independent reverse-transcriptase PCR experiments, with validation rates of 70-85%. Our analysis method also enables hierarchical clustering of genes and samples by the level of similarity to their alternative splicing patterns, revealing patterns of tissue-specific regulation that are distinct from those obtained by hierarchical clustering of gene expression from the same microarray data. Our data and analysis source code are available from http://www.bioinformatics.ucla.edu/ASAP.
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PMID:Detecting tissue-specific regulation of alternative splicing as a qualitative change in microarray data. 1559 20