Biomedical subjects

Kaman Chan

Publications and source records attributed to Kaman Chan.

4 recordsLinked to original sources

PubMed2003

Genomic comparison of Salmonella enterica serovars and Salmonella bongori by use of an S. enterica serovar typhimurium DNA microarray.

The genus Salmonella consists of over 2,200 serovars that differ in their host range and ability to cause disease despite their close genetic relatedness. The genetic factors that influence each serovar's level of host adaptation, how they evolved or were acquired, their influence on the evolution of each serovar, and the phylogenic relationships between the serovars are of great interest as they provide insight into the mechanisms behind these differences in host range and disease progression. We have used an Salmonella enterica serovar Typhimurium spotted DNA microarray to perform genomic hybridizations of various serovars and strains of both S. enterica (subspecies I and IIIa) and Salmonella bongori to gain insight into the genetic organization of the serovars. Our results are generally consistent with previously published DNA association and multilocus enzyme electrophoresis data. Our findings also reveal novel information. We observe a more distant relationship of serovar Arizona (subspecies IIIa) from the subspecies I serovars than previously measured. We also observe variability in the Arizona SPI-2 pathogenicity island, indicating that it has evolved in a manner distinct from the other serovars. In addition, we identify shared genetic features of S. enterica serovars Typhi, Paratyphi A, and Sendai that parallel their unique ability to cause enteric fever in humans. Therefore, whereas the taxonomic organization of Salmonella into serogroups provides a good first approximation of genetic relatedness, we show that it does not account for genomic changes that contribute to a serovar's degree of host adaptation.

Bacterial Proteins↗

PubMed2002

Improved analytical methods for microarray-based genome-composition analysis.

BACKGROUND: Whereas genome sequencing has given us high-resolution pictures of many different species of bacteria, microarrays provide a means of obtaining information on genome composition for many strains of a given species. Genome-composition analysis using microarrays, or 'genomotyping', can be used to categorize genes into 'present' and 'divergent' categories based on the level of hybridization signal. This typically involves selecting a signal value that is used as a cutoff to discriminate present (high signal) and divergent (low signal) genes. Current methodology uses empirical determination of cutoffs for classification into these categories, but this methodology is subject to several problems that can result in the misclassification of many genes. RESULTS: We describe a method that depends on the shape of the signal-ratio distribution and does not require empirical determination of a cutoff. Moreover, the cutoff is determined on an array-to-array basis, accounting for variation in strain composition and hybridization quality. The algorithm also provides an estimate of the probability that any given gene is present, which provides a measure of confidence in the categorical assignments. CONCLUSIONS: Many genes previously classified as present using static methods are in fact divergent on the basis of microarray signal; this is corrected by our algorithm. We have reassigned hundreds of genes from previous genomotyping studies of Helicobacter pylori and Campylobacter jejuni strains, and expect that the algorithm should be widely applicable to genomotyping data.

Algorithms↗

PubMed2002

Complex pattern of Mycobacterium marinum gene expression during long-term granulomatous infection.

During latent infection of humans with Mycobacterium tuberculosis, bacteria persist in the asymptomatic host within granulomas, organized collections of differentiated macrophages, and other immune cells. The mechanisms for persistence remain poorly understood, as is the metabolic and replicative state of the microbes within granulomas. We analyzed the gene expression profile of Mycobacterium marinum, the cause of fish and amphibian tuberculosis, during its persistence in granulomas. We identified genes expressed specifically when M. marinum persists within granulomas. These granuloma-activated genes were not activated in vitro in response to various conditions postulated to be operant in tuberculous granulomas, suggesting that their granuloma-specific activation was caused by complex conditions that could not be mimicked in vitro. In addition to the granuloma-activated genes, the bacteria resident in granulomas expressed a wide range of metabolic and synthetic genes that are expressed during logarithmic growth in laboratory medium. Our results suggest a dynamic host-pathogen interaction in the granuloma, where metabolically active bacteria are kept in check by the host immune system and where the products of granuloma-specific bacterial genes may thwart the host's attempt to completely eradicate the bacteria.

Acids↗

PubMed2002

Redefining bacterial populations: a post-genomic reformation.

Sexual reproduction and recombination are essential for the survival of most eukaryotic populations. Until recently, the impact of these processes on the structure of bacterial populations has been largely overlooked. The advent of large-scale whole-genome sequencing and the concomitant development of molecular tools, such as microarray technology, facilitate the sensitive detection of recombination events in bacteria. These techniques are revealing that bacterial populations are comprised of isolates that show a surprisingly wide spectrum of genetic diversity at the DNA level. Our new awareness of this genetic diversity is increasing our understanding of population structures and of how these affect host pathogen relationships.

Bacteria↗