Whole genome tiling arrays

			Personnel Ron W. Davis (PI) Ted Jones Jochen Kumm Curtis Palm

Whole genome tiling arrays (WGA) use array-based hybridyzation to scan the entire genome of an organism. This is achieved by using a set of overlapping oligonucleotide probes representing the whole genome. This new technology has many applications, such as novel gene discovery, gene expression studies, and discovery of transcription binding sites. WGAs are available for Arabidopsis thaliana and E.coli, and other WGAs, namely yeast and human, are under development. Through use in model organisms and then in humans WGAs will likely be a powerful new tool in biomedical research.

Experience with these WGA arrays coupled with a strong knowledge base and technical expertise at the Stanford Genome Technology Center provide an opportunity to develop bioinformatics tools for several applications of this new technology. We will also develop user interfaces to allow biologists to manage and visualize the WGA data together with public annotation sources or curated genomic information. The software, written in JAVA, will be freely distributed through a web interface. The amount and complexity of data produced by these arrays requires computational software to analyze the results. We propose to develop software applications that use WGA probe intensity data to reliably and reproducibly measure the presence or absence of signals, and by inference target sequences, in a sample. Using this as a starting point, we will apply it to exon prediction and annotation validation. Arabidopsis thaliana will be used as the main model system for development of this software, since whole genome arrays for this species has been designed, fabricated and tested (Yamada et al. Science, Vol 302, Issue 5646, 842-846, 31 October 2003) and are available to us.

In the second stage of the project we will analyze WGA data for the yeast S. cervisiae. The transfer of tools to another organism will be used to test and improve portability of the software and analysis tools to different species. We will prioritize possible migration of the software to a human WGA by incorporating human genome annotation in the prototype. We will validate the software at the Stanford Genome Technology Center, in the laboratory of Sakis (at UC Berkeley) and in the functional genomics group of Dr. Steinmetz at the EMBL in Germany. This will enable us to establish that the software works on a variety of platforms.