Comparative Computing for Microbial Genome Design – Abstract

Chuan-Hsiung Chang

With the advent of genomics, currently there are totally around 1386 complete and ongoing genome sequencing projects around the world. Near two hundred and fifty microbial genomes have already been completely sequenced and other five hundreds more are currently underway. The availability of the tremendous amount of microbial whole genome sequences has no doubt opened up new avenues for genome-wide innovative and efficient industrial research. Genomes, particularly microbial genomes, are a rich, diverse model system from which fundamental biochemical and biophysical rules for cell proliferation and differentiation can be inferred and applied to the design of engineered genomes. We are establishing a Microbial Genome Design & Engineering (MGDE) framework that could decompose bacterial chromosome sequences into functional and dispensable modules according their genome organization through genome comparison analysis for genome engineering research. The motivation for this study is two-fold. First, to attain a better understanding of the extent of generality of the “genome blueprint” paradigm, by asking the question, “Can any well-designed genome that has a specific set of gene groups perform a specific programmed cellular function?” Second, the investigation of the application of engineered genomes as tools for improving agricultural products. Genome engineering can modify an organism to become more productive, more suitable for abominable environment, or even have special capabilities. In the past, to obtain such well-functioned species requires massive screening or mutations. Today, we have the possibility to engineer a genome like playing jigsaws or puzzles, or like putting electronic parts together and make them work as an electric engineer. The future success of many areas of biological study will depend greatly upon the ability to capitalize on the wealth of genetic and biochemical information currently being generated from the field of genomics. The engineering analysis of genome information will play a key role in these developments. The outcomes would include a genome comparison platform, data mining system and databases to discover and store the rules for genome organization and functional/dispensable modules; and ultimately rules for reorganization modules will be also generated. A rapid, semi-automated pipeline to annotate microbial genomes will be used, incorporating information from sequence similarity, patterns, and structures (including also the experimental results from literatures). The predictive and exploratory capability of our method will find applications in the biotechnological industry, such as bioprocess design, metabolic engineering, and application target identification. Additionally, emphasis will be placed on the concept of utilizing genome information to gain an understanding of cellular physiology. The entire hereditary blueprint of an organism can be determined, and a deep transition into genome-enabled biotechnological industry is occurring. Genome design and engineering will become the new genetics for deciphering the blueprint of life.