Analysis of DNA Sequences Generated with Next-Gen Technology

James Knowles is a professor and associate chair of research psychiatry and the behavioral sciences at the Zilkha Neurogenetic Institute of the USC Keck School of Medicine. His research interests include the genetic factors that predispose individuals to psychiatric illnesses, such as schizophrenia, bipolar disorder, and early-onset major depression.

Peter Laird is an associate professor of surgery, biochemistry, and molecular biology and the director of the USC Epigenome Center. His research focuses on the role of DNA methylation and other epigenetic mechanisms in cancer.

Knowles and Laird have teamed up to research the genetic and epigenetic basis of a range of diseases, including colorectal, ovarian, prostate, and esophageal cancers, as well as schizophrenia, bipolar disorder, and major depression. The focus of their research is on DNA sequence variations, which are known to predispose individuals to thousands of diseases, and epigenetic alterations, which mark areas of the genome for repression or active use.

Using a next-generation DNA sequencing machine that is capable of producing one billion pairs of DNA sequences every 48 hours, Knowles and Laird generate sample DNA sequences. HPCC resources allow them to map each of the generated sample DNA sequences to locations in the human reference DNA sequence.

Knowles uses this technology to determine whether the sample DNA sequences that do not exactly match the human reference DNA sequence represent DNA sequence variations that predispose individuals to disease. Locating these variations would represent a medical breakthrough that could lead to an enhanced understanding of the causes of disease and to focused research on possible cures.

Under the direction of Laird, the Epigenome Center uses HPCC resources for epigenetic analysis by counting the number of sequences found at different parts of the genome, after enrichment, for particular epigenetic marks. This allows researchers to identify epigenetic changes that have arisen in cancer tissues. Support for this research comes from the National Institute of Mental Health and the National Cancer Institute.