Biomedical subjects

Dafu Ding

Publications and source records attributed to Dafu Ding.

4 recordsLinked to original sources

PubMed2006

Increasing synthetic performance of penicillin G acylase from Bacillus megaterium by site-directed mutagenesis.

Site-directed mutagenesis based on predicted modeled structure of pencillin G acylase from Bacillus megaterium (BmPGA) was followed to increase its performance in the kinetically controlled synthesis of cephalexin with high reactant concentrations of 133 mM 7-amino-desaceto-xycephalosporanic acid (7-ADCA) and 267 mM D: -phenylglycine amide (D-PGA). We directed changes in amino acid residues to positions close to the active site that were expected to affect the catalytic performance of penicillin acylase: alpha Y144, alpha F145, and beta V24. Alpha F145 was mutated into tyrosine, alanine, and leucine. Alpha Y144 and beta V24 were mutated into arginine and phenylalanine, respectively. The S/H ratios of three mutants, BmPGAalpha144R, BmPGAbeta24F, and BmPGAbeta24F+alpha144R, were up to 1.3-3.0 times higher values. Compared to the wild-type BmPGA, BmPGAbeta24F+alpha144R showed superior potential of the synthetic performance, allowing the accumulation of up to twofold more cephalexin at significantly higher conversion rates.

Amino Acids↗

PubMed2004

Learning module networks from genome-wide location and expression data.

We develop a systematic algorithm for discovering network of regulatory modules, which identifies regulatory modules and their regulation program by integrating genome-wide location and expression data. Unlike previous approaches [Eisen, M.B., Spellman, P.T., Brown, P.O. and Botstein, D. (1998) Proc. Natl. Acad. Sci. USA 95, 14863-14868; Tavazoie, S., Hughes, J.D., Campbell, M.J., Cho, R.J. and Church, G.M. (1999) Nat. Genet. 22, 281-285; Ihmels, J., Friedlander, G., Bergmann, S., Sarig, O., Ziv, Y. and Barkai, N. (2002) Nat. Genet. 31, 370-377; Segal, E., Shapira, M., Regev, A., Pe'er, D., Botstein, D., Koller, D. and Friedman, N. (2003) Nat. Genet. 34, 166-176] that relied primarily on gene expression data, our algorithm regards the regulator binding data as prior knowledge that provide direct evidence of physical regulatory interactions. We applied the method to a Saccharomyces cerevisiae genome-wide location data [Lee, T.I., Rinaldi, N.J., Robert, F., Odom, D.T., Bar-Joseph, Z., Gerber, G.K., Hannett, N.M., Harbison, C.T., Thompson, C.M., Simon, I., Zeitlinger, J., Jennings, E.G., Murray, H.L. Gordon, D.B., Ren, B., Wyrick, J.J., Tagne, J.B., Volkert, T.L., Fraenkel, E., Gifford, D.K. and Young, R.A. (2002) Science 298, 799-804] for 106 DNA-binding transcription factors and 250 gene expression experiments under the conditions from the cell cycle to responses to various stress conditions. The results show that our method is able to identify functionally coherent modules and their proper regulators. Supplementary materials are available at http://compbio.sibnet.org/projects/module-network/.

Algorithms↗

PubMed2004

MedBlast: searching articles related to a biological sequence.

UNLABELLED: In the genomic era, researchers often want to know more information about a biological sequence by retrieving its related articles. However, there is no available tool yet to achieve conveniently this goal. Here we developed a new literature-mining tool MedBlast, which uses natural language processing techniques, to retrieve the related articles of a given sequence. An online server of this program is also provided. AVAILABILITY: Both online server and the program are available freely at http://medblast.sibsnet.org

Algorithms↗

PubMed2003

Detecting pathogenicity islands and anomalous gene clusters by iterative discriminant analysis.

We present a simple method to detect pathogenicity islands and anomalous gene clusters in bacterial genomes. The method uses iterative discriminant analysis to define genomic regions that deviate most from the rest of the genome in three compositional criteria: G+C content, dinucleotide frequency and codon usage. Using this method, we identify many virulence-related gene islands, e.g. encoding protein secretion systems, adhesins, toxins, and other anomalous gene clusters, such as prophages. The program and the whole dataset, including the catalogs of genes in the detected anomalous segments, are publicly available at http://compbio.sibsnet.org/projects/pai-ida/. This program can be used in searching for virulence-related factors in newly sequenced bacterial genomes.

Algorithms↗