My research interest has been the development of sophisticated computer algorithms to efficiently solve large scale biological research problems. For example, I have developed the automatic DNA sequence clean up programs (LUCY1 & 2) for genomic research, the efficient whole-genome oligo microarray design tool (PICKY) for post-genomic research, and the automatic Perl programming tool (VECT) for biologists. My software tools usually employ novel approaches to computing and provide better results than previous solutions. For example, while most microarray design tools are still based on sequence-level comparison (e.g., BLAST) to screen out nontargets, my PICKY program has embedded a complete suite of thermodynamic equations in its calculations to infer the best oligo candidates based on physics, and it does so orders of magnitude faster than any other comparable microarray design tools with comparable computation depth. My recent research focus is on the computer-aided biological research area. This area differs from computational biology in that the end goals are still the successes in molecular biology, but the approach are greatly improved (both in efficiency and chance of success) by using computer analyses. A good example of this new type of research is the whole-genome siRNA design approach we have conducted using Picky and we have validated (in actual bench experiments) that our computer-aided siRNA design indeed greatly reduces the off-target effects of the experiments.
Ongoing projects: National Science Foundation (NSF) has awarded a grant for the research project entitled "Optimal siRNA Design Based on Whole Genome Thermodynamic Analysis" to start in September 2009. RNA interference (RNAi) is a natural phenomenon in cells where siRNAs guide the recognition, inhibition and potential degradation of target messenger RNAs (mRNAs), resulting in the loss of their gene functions. RNAi is an important molecular biology technology that can be used to perform functional genomic studies. It is also suggested that siRNAs can be used as drugs to stop oncogenes in cancer cells or to fight off viruses. The two main goals of this project are to create novel siRNA design software that can select high quality, gene-specific siRNAs based on the comprehensive thermodynamic analysis of an entire genome and to validate the quality of the designed siRNAs with RNAi experiments.