At recent years, I put my focuses on following important issues, (1) Deciphering the protein network in the approach in Network biology and Systems Biology (2) Developing value-added databases and web applications for biomedical research communities, (3) Metagenomics.
        (1) Network analysis of human protein interactions for Tumorigenesis and infectious diseases in the approach of systems biology: Advances in molecular biology, analytical and computational technologies are enabling us to investigate systematically on complicate molecular processes through protein interaction networks underlying biological phenotypes. In this study, we are going to construct the eukaryotic proteinprotein interaction network from recently high though-put interactome studies from various species. All the interactions will be converted into domain-domain interactions and then the conserved network motifs will be extracted to infer protein interactome related to human diseases. Using this model, we will build a powerful tool to discover unknown interacting protein pairs with a probability score. According to the conserved network model with spatiotemporal information, the interactions between pathogens and human and the procession of carcinogenesis will be deciphered. The critical target proteins in those networks will be unrevealed by the topological analysis of protein network. The interaction network will provide potential candidates for developing new therapeutic strategies of human cancer and infectious diseases. Objectives of this study are to improve our understanding of the puzzle during development stage, carcinogenesis and infectious mechanism, and to furthermore introduce a new paradigm for the diagnosis and treatment of human disease to revolutionize current medical services delivered. Our previous works on protein networks were published (Please see publication list) including integration networks in Helicobacter pylori (http://dpi.nhri.org.tw/hp) and Dosophila melanogaster (http://fly.nhri.org.tw/) on Bioinformatics and BMC Bioinformatics, respectively. Based on the strategy of evolutionary conservation, our team has conducted an algorithm to infer the interaction of human protein pairs. The predicted human proteinprotein interactions associated with confidence scores are derived from six eukaryotic organisms – rat, mouse, fly, worm, Arabidopsis thaliana and baker’s yeast. This work was published and marked with “Highly Accessed” by BMC Bioinformatics since May 2007. The web database for representation of human interactome is under construction.
        (2) Developing value-added databases and web applications for biomedical research communities: We have published several web applications and databases related with bioinformatics for biomedical research community. For example, the web application, Primer Design Assistant (PDA, http://dbb.nhri.org.tw/primer/, Nucleic Acid Res. 2004), can be helpful to large scale PCR for high throughput experiments like microarray experiments. From July 2003 to Mar 2008, the accumulated visits and processed sequences are 100,000 and 550,000, respectively. PDA is not only served for research groups, but also was used to develop the rapid diagnostic kit for SARS for Central of Disease Control (CDC), Taiwan in 2004. Until now, there are several diagnostic kits developed by PDA. Based on similar idea, we have implemented a platform for unique probe design for various uses in hybridization, like microarray and blots. This system named as “Unique Probe Selector, UPS” can be accessed freely at http://array.iis.sinica.edu.tw/ups and published on BMC Bioinformatics (2008).
        We also implemented a statistical model into our protein interaction database for validation of two-hybrid assays of Helicobacter pylori , and prediction of putative protein interactions not yet discovered experimentally. By this approach, we can compare the interacting network of various strains with different virulence to decipher the secret between hosts and pathogens. This work was published on Bioinformatics, 2005 and can be accessed on http://dpi.nhri.org.tw/hp/. Using the more sophisticated statistical method with expression profile, we integrated a database named as flydpi for the interactome of Drosophila Melanogaster(http://flydpi.nhri.org.tw, BMC Bioinformatics, 2006). In 2005, we have implemented a phylogenetic platform for topology construction and visualization. This website can be found on http://power.nhri.org.tw and published on Nucleic Acid Research, 2005. We are working on the best model selection in automatic way and try to integrate two systems for biomedical research groups.
        (3) Metagenomics: According to the advance in sequencing technology, time for sequencing large genome like human genome would not take several months/years but weeks/days. By using “shotgun” Sanger sequencing or chip-based pyrosequencing to get(mostly) unbiased samples of all genes from all membersof sampled communities, we can start to under the genetic material recovered directly from environmental samples. Such kind of work can’t be done in traditional microbiology and microbial genome sequencing relied upon cultivated clonal cultures. Several shotgun sequencing projects of various communities have been completed and started. Following the flood of massive sequence data, there are several interesting computational problems that arise from WGS sequencing of communities. Those issues related with how to compare communities, how to separate sequence from different organisms in silico, and how to model population structures using WGS assembly statistics, will be new challenges in the field of bioinformatics. Our approach here is to integrate various databases, gene expression analysis, proteomic results and phylogenetic reconstruction to achieve a comprehensive view of microbial communities.