RESUMO
The development of the HUPO-PSI's (Proteomics Standards Initiative) standard data formats and MIAPE (Minimum Information About a Proteomics Experiment) guidelines should improve proteomics data sharing within the scientific community. Proteomics journals have encouraged the use of these standards and guidelines to improve the quality of experimental reporting and ease the evaluation and publication of manuscripts. However, there is an evident lack of bioinformatics tools specifically designed to create and edit standard file formats and reports, or embed them within proteomics workflows. In this article, we describe a new web-based software suite (The ProteoRed MIAPE web toolkit) that performs several complementary roles related to proteomic data standards. First, it can verify that the reports fulfill the minimum information requirements of the corresponding MIAPE modules, highlighting inconsistencies or missing information. Second, the toolkit can convert several XML-based data standards directly into human readable MIAPE reports stored within the ProteoRed MIAPE repository. Finally, it can also perform the reverse operation, allowing users to export from MIAPE reports into XML files for computational processing, data sharing, or public database submission. The toolkit is thus the first application capable of automatically linking the PSI's MIAPE modules with the corresponding XML data exchange standards, enabling bidirectional conversions. This toolkit is freely available at http://www.proteored.org/MIAPE/.
Assuntos
Proteômica/normas , Software , Estatística como Assunto , Biologia Computacional/normas , Humanos , Disseminação de Informação , Internet , Espectrometria de Massas , Editoração/normasRESUMO
BACKGROUND: Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. METHOD: The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. RESULTS: The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer. The strongest risk factors were found in the AA genotype and allele of SNP rs3892097 from the CYP2D6 gene, followed by the alleles A and T of SNPs rs2740574 and rs2687116, respectively from CYP3A4. The most important concomitance was between homozygous genotype AA of rs3892097 and genotype AA of rs2740574 with 78.3% in drug-resistant epilepsy patients as compared to 14.3% in control patients. CONCLUSION: The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing drug resistance and CYP2D6, CYP2C19 SNPs and haplotypes may affect the response to antiepileptic drugs.
Assuntos
Anticonvulsivantes/administração & dosagem , Citocromo P-450 CYP3A/genética , Epilepsia/tratamento farmacológico , Farmacogenética , Adolescente , Alelos , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/farmacologia , Criança , Pré-Escolar , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2D6/genética , Resistência a Medicamentos , Epilepsia/genética , Feminino , Variação Genética , Genótipo , Humanos , Lactente , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Several factors, including pharmacogenetics, contribute to inter-individual variability in drug response. Many antiepileptic drugs (AEDs) are metabolized by a variety of enzymatic reactions, and the cytochrome P450 (CYP) family has attracted considerable attention. Some of the CYPs exist as genetic (allelic) variants, which may also affect the plasma concentrations or drug exposure. Regarding the metabolism of AEDs, the polymorphic CYP2C9 and CYP2C19 are of particular interest. There have been recent advances in discovering factors such as these, especially those underlying the risk of medication toxicity. This review summarizes the evidence about whether such polymorphisms affect the clinical action of AEDs to facilitate future studies on the pharmacogenetics of epilepsy. We performed Key Words searches in the public databases PubMed, Medscape, and Rxlisty, Pharm GKB for genetic polymorphisms and the NCBI website for the nomenclature of alleles of CYP450, finding that CYP2D6, CYP2C9, CYP3A4, and CYP2D19 were involved in the metabolism of most antiepileptic drugs, given the allele frequency in the population and the associated variability in the clinical response.