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2006 Scientific Report

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Van Andel Research

Van Andel Research Institute | Scientific Report Kyle A. Furge, Ph.D. Laboratory of Computational Biology 24 Dr. Furge received his Ph.D. in biochemistry from the Vanderbilt University School of Medicine in 2000. Prior to obtaining his degree, he worked as a software engineer at YSI, Inc., where he wrote operating systems for embedded computer devices. Dr. Furge did his postdoctoral work in the laboratory of Dr. George Vande Woude. He became a Bioinformatics Scientist at VARI in June of 2001 and a Scientific Investigator in May of 2005. Staff Laboratory Staff Karl Dykema, B.A.

VARI | 2006 Research Interests As high-throughput technologies such as DNA sequencing, gene expression microarrays, and genotyping become more available to researchers, analyzing the large amount of data produced by these technologies becomes difficult. Computational disciplines such as bioinformatics and computational biology have emerged to develop methods that assist in the storage, distribution, integration, and analysis of these large data sets. The Computational Biology laboratory at VARI currently focuses on using mathematical and computer science approaches to analyze and integrate complex data sets in order to develop a better understanding of how cancer cells differ from normal cells at the molecular level. In addition, members of the lab provide assistance in data analysis and other computational projects on a collaborative and/or fee-for-service basis. In the past year the laboratory has worked on many projects to further the research efforts at VARI. For example, we continue to work closely with the Microarray Technology laboratory (MT) on the analysis and management of gene expression microarray chips and data sets. The MT lab manages more than 100,000 unique DNA fragments that are used to monitor gene expression in organisms including canines, rats, mice, and humans. As the knowledge of the sequence information from each species evolves, our group helps provide up-to-date information for each of these fragments. In addition, we constructed a quality assurance program to help the MT lab monitor the gene expression data that is being generated by their group. In another project, we assisted VARI’s Michael Weinreich in performing sequence analysis across multiple species to identify a potentially new protein-binding domain. We also continue our active involvement in larger projects that have resulted in collaborative grants with Jim Resau, Nick Duesbury, and Bin Teh. 25 Providing assistance to other investigators is one focus of the laboratory. We also have a special research focus on understanding how cytogenetic abnormalities influence cancer development and progression. Many cancer types are associated with defined sets of DNA gains and losses. For example, the majority of hepatocellular carcinomas contain extra copies of chromosome 1p and lack copies of chromosome 4q. In contrast, the majority of clear cell renal cell carcinomas contain an extra copy of chromosome 5q and lack a copy of chromosome 3p. Because of the recurrent appearance of certain chromosomal gains and losses, it is reasonable to hypothesize that those disruptions are important to tumor development and progression. Over the past years, we have developed and evaluated computational methods to indirectly identify the chromosomal gains and losses that occur in tumor samples by examining the gene expression data. Then we examine regions of chromosomal gain or loss for misregulation of single genes within the region of abnormality. In addition, we are developing and evaluating methods to determine if a large number of genes that are associated with a particular oncogenic pathway show changes in expression following a chromosomal abnormality. From this type of analysis, we then infer which pathways may be affected by the abnormality.

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