Biomedical subjects

Jer-Ming Chia

Publications and source records attributed to Jer-Ming Chia.

7 recordsLinked to original sources

PubMed2005

A population-based LD map of the human chromosome 6p.

The recent publication of the complete sequence of human chromosome 6 provides a platform from which to investigate genomic sequence variation. We report here a detailed linkage disequilibrium (LD) pattern map across the entire human chromosome 6p by using a set of 1152 single nucleotide polymorphisms (SNPs) in a population of 198 Singaporean Chinese, with 326 SNPs focused in the major histocompatibility complex (MHC) region. Our analysis shows some unexpectedly high segments of strong LD in a 10-Mb region that includes the extremely polymorphic and gene-rich MHC loci and many non-MHC genes. These include the telomeric peri-MHC region that harbors olfactory receptors, histones and zinc finger clusters, and the centromeric peri-MHC region that contains several unknown open reading frames. The data also help refine a human-mouse synteny break in the region between 28.6 and 29.4 Mb. The population-based LD map presented here will provide an essential resource for understanding the genomic sequence variation of chromosome 6p and LD mapping of disease genes of complex genetic traits.

Chromosome Mapping↗

PubMed2004

Implications for domain fusion protein-protein interactions based on structural information.

BACKGROUND: Several in silico methods exist that were developed to predict protein interactions from the copious amount of genomic and proteomic data. One of these methods is Domain Fusion, which has proven to be effective in predicting functional links between proteins. RESULTS: Analyzing the structures of multi-domain single-chain peptides, we found that domain pairs located less than 30 residues apart on a chain are almost certain to share a physical interface. The majority of these interactions are also conserved across separate chains. We make use of this observation to improve domain fusion based protein interaction predictions, and demonstrate this by implementing it on a set of Saccharomyces cerevisiae proteins. CONCLUSION: We show that existing structural data supports the domain fusion hypothesis. Empirical information from structural data also enables us to refine and assess domain fusion based protein interaction predictions. These interactions can then be integrated with downstream biochemical and genetic assays to generate more reliable protein interaction data sets.

Amino Acids↗

PubMed2004

A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection.

BACKGROUND: The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. METHODS: PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. RESULTS: We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. CONCLUSIONS: The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis.

Animals↗

PubMed2004

Fugu genome analysis provides evidence for a whole-genome duplication early during the evolution of ray-finned fishes.

With about 24,000 extant species, teleosts are the largest group of vertebrates. They constitute more than 99% of the ray-finned fishes (Actinopterygii) that diverged from the lobe-finned fish lineage (Sarcopterygii) about 450 MYA. Although the role of genome duplication in the evolution of vertebrates is now established, its role in structuring the teleost genomes has been controversial. At least two hypotheses have been proposed: a whole-genome duplication in an ancient ray-finned fish and independent gene duplications in different lineages. These hypotheses are, however, based on small data sets and lack adequate statistical and phylogenetic support. In this study, we have made a systematic comparison of the draft genome sequences of Fugu and humans to identify paralogous chromosomal regions ("paralogons") in the Fugu that arose in the ray-finned fish lineage ("fish-specific"). We identified duplicate genes in the Fugu by phylogenetic analyses of the Fugu, human, and invertebrate sequences. Our analyses provide evidence for 425 fish-specific duplicate genes in the Fugu and show that at least 6.6% of the genome is represented by fish-specific paralogons. We estimated the ages of Fugu duplicate genes and paralogons using the molecular clock. Remarkably, the ages of duplicate genes and paralogons are clustered, with a peak around 350 MYA. These data strongly suggest a whole-genome duplication event early during the evolution of ray-finned fishes, probably before the origin of teleosts.

Animals↗

PubMed2003

Biopipe: a flexible framework for protocol-based bioinformatics analysis.

We identify several challenges facing bioinformatics analysis today. Firstly, to fulfill the promise of comparative studies, bioinformatics analysis will need to accommodate different sources of data residing in a federation of databases that, in turn, come in different formats and modes of accessibility. Secondly, the tsunami of data to be handled will require robust systems that enable bioinformatics analysis to be carried out in a parallel fashion. Thirdly, the ever-evolving state of bioinformatics presents new algorithms and paradigms in conducting analysis. This means that any bioinformatics framework must be flexible and generic enough to accommodate such changes. In addition, we identify the need for introducing an explicit protocol-based approach to bioinformatics analysis that will lend rigorousness to the analysis. This makes it easier for experimentation and replication of results by external parties. Biopipe is designed in an effort to meet these goals. It aims to allow researchers to focus on protocol design. At the same time, it is designed to work over a compute farm and thus provides high-throughput performance. A common exchange format that encapsulates the entire protocol in terms of the analysis modules, parameters, and data versions has been developed to provide a powerful way in which to distribute and reproduce results. This will enable researchers to discuss and interpret the data better as the once implicit assumptions are now explicitly defined within the Biopipe framework.

Amino Acid Sequence↗

PubMed2003

Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection.

BACKGROUND: The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis of various isolates might provide an indication of potential strain differences of this new virus. Moreover, mutation analysis will help to develop effective vaccines. METHODS: We sequenced the entire SARS viral genome of cultured isolates from the index case (SIN2500) presenting in Singapore, from three primary contacts (SIN2774, SIN2748, and SIN2677), and one secondary contact (SIN2679). These sequences were compared with the isolates from Canada (TOR2), Hong Kong (CUHK-W1 and HKU39849), Hanoi (URBANI), Guangzhou (GZ01), and Beijing (BJ01, BJ02, BJ03, BJ04). FINDINGS: We identified 129 sequence variations among the 14 isolates, with 16 recurrent variant sequences. Common variant sequences at four loci define two distinct genotypes of the SARS virus. One genotype was linked with infections originating in Hotel M in Hong Kong, the second contained isolates from Hong Kong, Guangzhou, and Beijing with no association with Hotel M (p<0.0001). Moreover, other common sequence variants further distinguished the geographical origins of the isolates, especially between Singapore and Beijing. INTERPRETATION: Despite the recent onset of the SARS epidemic, genetic signatures are emerging that partition the worldwide SARS viral isolates into groups on the basis of contact source history and geography. These signatures can be used to trace sources of infection. In addition, a common variant associated with a non-conservative aminoacid change in the S1 region of the spike protein, suggests that immunological pressures might be starting to influence the evolution of the SARS virus in human populations.

Amino Acid Sequence↗

PubMed2002

Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes.

The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some "giant" genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match to Fugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.

Animals↗