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The article is a summary of the research done in GIS. It touches on the focus on systems and integrative biology and GIS's efforts in collaborating with international organizations.

High-throughput single nucleotide polymorphism (SNP) genotyping systems provide two kinds of fluorescent signals detected from different alleles. In current technologies, the process of genotype discrimination requires subjective judgments by expert operators, even when using clustering algorithms. Here, we propose two evaluation measures to manage fluorescent scatter data with nonclear plot aggregation. The first is the marker ranking measure, which provides a ranking system for the SNP markers based on the distance between the scatter plot distribution and a user-defined ideal distribution. The second measure, called individual genotype membership, uses the membership probability of each genotype related to an individual plot in the scatter data. In verification experiments, the marker ranking measure determined the ranking of SNP markers correlated with the subjective order of SNP markers judged by an expert operator. The experiment using the individual genotype membership measure clarified that the total number of unclassified individuals was remarkably reduced compared to that of manually unclassified ones. These two evaluation measures were implemented as the GTAssist software. GTAssist provides objective standards and avoids subjective biases in SNP genotyping workflows.

Current genotype-calling methods such as Robust Linear Model with Mahalanobis Distance Classifier (RLMM) and Corrected Robust Linear Model with Maximum Likelihood Classification (CRLMM) provide accurate calling results for Affymetrix Single Nucleotide Polymorphisms (SNP) chips. However, these methods are computationally expensive as they employ preprocess procedures, including chip data normalization and other sophisticated statistical techniques. In the small sample case the accuracy rate may drop significantly. We develop a new genotype calling method for Affymetrix 100 k and 500 k SNP chips. A two-stage classification scheme is proposed to obtain a fast genotype calling algorithm. The first stage uses unsupervised classification to quickly discriminate genotypes with high accuracy for the majority of the SNPs. And the second stage employs a supervised classification method to incorporate allele frequency information either from the HapMap data or from a self-training scheme. Confidence score is provided for every genotype call. The overall performance is shown to be comparable to that of CRLMM as verified by the known gold standard HapMap data and is superior in small sample cases. The new algorithm is computationally simple and standalone in the sense that a self-training scheme can be used without employing any other training data. A package implementing the calling algorithm is freely available at .

We report the development of a homogenous assay for the genotyping of single-nucleotide polymorphisms (SNPs), utilizing a fluorescent dsDNA-binding dye. Termed T_M-shift genotyping, this method combines multiplex allele-specific PCR with sequence differentiation based on the melting temperatures of amplification products. Allele-specific primers differing in length were used with a common reverse primer in a single-tube assay. PCR amplification followed by melt curve analysis was performed with a fluorescent dsDNA-binding dye on a real-time capillary thermocycler. Genotyping was carried out in a single-tube homogeneous assay in 25 minutes. We compared the accuracy and efficiency of this T_M genotyping method with conventional restriction fragment genotyping of a novel single nucleotide polymorphism in the Jagged1 (JAG1) gene. The flexibility, economy and accuracy of this new method for genotyping polymorphisms could make it useful for a variety of research and diagnostic applications.

Polymorphic acetylation of drug and xenobiotics is a known cause of interindividual variability in drug pharmacokinetics and in the risk of developing adverse drug events. Acetylation ability is strongly linked to variations in the arylamine N-acetyltransferase 2 (NAT2) gene, and several procedures have been developed to predict acetylation phenotypes based on genetic tests. This chapter analyses the most salient issues inherent to NAT2 genotyping, haplotype reconstruction and phenotype inference, as well as the clinical implications of the polymorphic acetylation of drugs such as aminoglutethimide, amonafide, caffeine, clonazepam, dapsone, hydralazine, isoniazid, metamizole, nitrazepam, phenelzine, phenytoin, procainamide, sulfamethazine, sulfamethoxazole and sulfasalazine. These drugs and/or their metabolites are polymorphically acetylated, and for many of these drugs, acetylation status (either phenotype or genotype) causes pharmacokinetic changes and often adverse drug events. We identify potential areas needing additional research before NAT2 genetic testing can be used for the development of clinical practice pharmacogenomics guidelines.

The aim of this study was to evaluate the susceptibility to antibiotics and quaternary ammonium disinfectants of Acinetobacter baumannii strains isolated from patients with nosocomial infections and the environment of the ICU and Neonatal Service (NS) at the Caracas University Hospital. Resistance to 15 antibiotics was determined. To evaluate the disinfectant resistance phenotypes tests recommended by the AOAC were used. ERIC-PCR and REP-PCR were used for genotyping. We analyzed 74 A. baumannii, 14 and 1 from ICU and NS patients, respectively; and 42 and 17 from its corresponding environments. 44.6% of the isolates showed resistance to at least 7 antibiotics. 54% of isolates tested exhibited the resistance phenotypes to the quaternary ammonium hospital disinfectant evaluated. 73% of the isolates from patients were closely related clones, 28.8% of the environmental isolates were grouped in 7 indistinguishable clones groups. The multiple antibiotic and disinfectant resistance profiles and the presence of related bacterial clones demonstrate the need for antibiotic usage surveillance and alternative cleaning methods in this hospital.