Project Report

Background A genome describes all the genes in an organism. Genes are the ingredients of a cell, describing which proteins will eventually be synthesized by the cell and subsequently used in cellular processes. Recent advances in genome sequencing technologies have enabled the use of whole-genome sequencing for research purposes. Intellectual Merit In this project, we utilized whole-genome sequencing to measure changes in the amount of each gene in the genome, termed gene copy number. It is possible to either lose or gain copies of genes. This occurs when regions of the genome, in particular different parts of chromosomes, are amplified or removed. Chromosomes are the physical organizing centers of the genome. Different genes are located on different chromosomes. By measuring copy number changes across many tumors, we are able to identify patterns of copy number gain or loss that occur across many tumors. Rather than focusing on just a few genes, we considered many genes at once in a multivariate fashion. By doing this, we were able to capture dependencies between different genes that were collectively or independently observed in tumors. Broader Impacts The results from these multivariate approaches were compared between two different cancer types, and in various cancer cell lines. The results suggest shared fundamental mechanisms for how cells transition from a normal state to a cancerous state. These findings improve our understanding of chromosome biology and function, and also have implications for the discovery of cancer therapeutics. As whole-genome sequencing becomes cost effective for individual patients, this work provides a potential framework for identifying patient-specific therapeutic regimens. Results from this work were presented in seminars at the Genome Institute of Singapore and the Massachusetts Institute of Technology. It is anticipated that future results stemming from this work will be presented at national conferences. This work has fostered an international collaboration between Singapore and the US. It has exposed researchers in Singapore to the computational methods used by the PI, and it has exposed the PI to the experimental methods and data studied in Singapore. Moving forward, contacts and relationships established during this program will continue to foster research progress, especially as the PI intends to continue studying this research topic after completing his PhD. Acknowledgements This eight-week project was carried out as part of the East Asia and Pacific Summer Institutes (EAPSI) program in Singapore, in collaboration with the National University of Singapore and the Genome Institute of Singapore. The project was generously supported by the US National Science Foundation and the Singapore National Research Foundation.

Agency
National Science Foundation (NSF)
Institute
Office of International and Integrative Activities (IIA)
Application #
1108282
Program Officer
Carter Kimsey
Project Start
Project End
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
Fiscal Year
2011
Total Cost
$5,700
Indirect Cost
Name
Wagner Joel P
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02138