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Biomedical subjects

Z Q Tang

Publications and source records attributed to Z Q Tang.

7 recordsLinked to original sources

PharmGED: Pharmacogenetic Effect Database.

Prediction and elucidation of pharmacogenetic effects is important for facilitating the development of personalized medicines. Knowledge of polymorphism-induced and other types of drug-response variations is needed for facilitating such studies. Although databases of pharmacogenetic knowledge, polymorphism and toxicogenomic information have appeared, some of the relevant data are provided in separate web-pages and in terms of relatively long descriptions quoted from literatures. To facilitate easy and quick assessment of the relevant information, it is helpful to develop databases that provide all of the information related to a pharmacogenetic effect in the same web-page and in brief descriptions. We developed a database, Pharmacogenetic Effect Database (PharmGED), for providing sequence, function, polymorphism, affected drugs and pharmacogenetic effects. PharmGED can be accessed at http://bidd.cz3.nus.edu.sg/phg/ free of charge for academic use. It currently contains 1825 entries covering 108 disease conditions, 266 distinct proteins, 693 polymorphisms, 414 drugs/ligands cited from 856 references.

Animals↗

Prediction of MHC-binding peptides of flexible lengths from sequence-derived structural and physicochemical properties.

Peptide binding to MHC is critical for antigen recognition by T-cells. To facilitate vaccine design, computational methods have been developed for predicting MHC-binding peptides, which achieve impressive prediction accuracies of 70-90% for binders and 40-80% for non-binders. These methods have been developed for peptides of fixed lengths, for a limited number of alleles, trained from small number of non-binders, and in some cases based straightforwardly on sequence. These limit prediction coverage and accuracy particularly for non-binders. It is desirable to explore methods that predict binders of flexible lengths from sequence-derived physicochemical properties and trained from diverse sets of non-binders. This work explores support vector machines (SVM) as such a method for developing prediction systems of 18 MHC class I and 12 class II alleles by using 4208-3252 binders and 234,333-168,793 non-binders, and evaluated by an independent set of 545-476 binders and 110,564-84,430 non-binders. Binder accuracies are 86-99% for 25 and 70-80% for 5 alleles, non-binder accuracies are 96-99% for 30 alleles. Binder accuracies are comparable and non-binder accuracies substantially improved against other results. Our method correctly predicts 73.3% of the 15 newly-published epitopes in the last 4 months of 2005. Of the 251 recently-published HLA-A*0201 non-epitopes predicted as binders by other methods, 63 are predicted as binders by our method. Screening of HIV-1 genome shows that, compared to other methods, a comparable percentage (75-100%) of its known epitopes is correctly predicted, while a lower percentage (0.01-5% for 24 and 5-8% for 6 alleles) of its constituent peptides are predicted as binders. Our software can be accessed at .

Alleles↗

An evaluation of para toluene-sulfonamide metabolism and effect with regard to CYP isoforms, P-glycoprotein, and drug interactions.

Aim of this study was to investigate liver metabolism of with regard to para toluene-sulfonamide (PTS), CYP isoforms, P-glycoprotein (P-gp), and drug interactions. Known substrates, inducers and inhibitors of CYP and inhibitor of P-gp were employed and metabolites were determined with HPLC. Male Wistar rats were pretreated with ip phenobarbital (PB), ketoconazole (Ket), or verapamil (Ver) for 3 days and in situ liver perfusion of PTS was conducted in a recirculation system. Rats were also pretreated with ip PTS (33 mg x kg(-1) x d(-1) or PTS 99 mg x kg(-1) x d(-1)) for 4 days before liver perfusions with dextromethorphan (Dex) and phenacetin (Phe) preparations were conducted. Microsome incubation was used to investigate PTS effect on five CYP isoforms and PTS-drug interactions probability with phyllotoxin and 5-fluorouracil (5-FU) in vitro. PTS at 60 min perfusates had areas of 61.4% and 133.6% of the blank control in PB group and Ket group, respectively. The result that PTS metabolism was enhanced by PB and inhibited by Ket treatments suggested liver CYP was attributed to PTS metabolism. PTS 99 mg x kg(-1) x d(-1) pretreatment slowed down the metabolism of Dex and Phe while in vitro incubations did not show a PTS (0-160 micromol/L) effect on CYP activities. PTS metabolite formation when co-incubated with phyllotoxin was 50.7% of the negative control. The potent inhibitory ability of phyllotoxin to PTS requires further clinical investigation regarding in concomitant administration.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prediction of functional class of novel plant proteins by a statistical learning method.

In plant genomes, the function of a substantial percentage of the putative protein-coding open reading frames (ORFs) is unknown. These ORFs have no significant sequence similarity to known proteins, which complicates the task of functional study of these proteins. Efforts are being made to explore methods that are complementary to, or may be used in combination with, sequence alignment and clustering methods. A web-based protein functional class prediction software, SVMProt, has shown some capability for predicting functional class of distantly related proteins. Here the usefulness of SVMProt for functional study of novel plant proteins is evaluated. To test SVMProt, 49 plant proteins (without a sequence homolog in the Swiss-Prot protein database, not in the SVMProt training set, and with functional indications provided in the literature) were selected from a comprehensive search of MEDLINE abstracts and Swiss-Prot databases in 1999-2004. These represent unique proteins the function of which, at present, cannot be confidently predicted by sequence alignment and clustering methods. The predicted functional class of 31 proteins was consistent, and that of four other proteins was weakly consistent, with published functions. Overall, the functional class of 71.4% of these proteins was consistent, or weakly consistent, with functional indications described in the literature. SVMProt shows a certain level of ability to provide useful hints about the functions of novel plant proteins with no similarity to known proteins.

Artificial Intelligence↗