In a boost to cancer research, Princeton scientists have invented a fast and reliable method for identifying alterations to chromosomes that occur when cells become malignant. The technique helps to show how cells modify their own genetic makeup and may allow cancer treatments to be tailored more precisely to a patient's disease.
Cancer cells are known among biologists for their remarkable ability to disable some genes and overuse others, allowing their unchecked growth into tumors. The most aggressive of these distortions occurs when cells delete or multiply chunks of their own chromosomes. Cells can simply snip strings of genes from the chromosome, or make many extra copies of the string and reinsert it into the chromosome.
Until now, scientists had no routine way to detect these alterations except for very large-scale deletions or additions. Finding small, but critical additions or deletions to chromosomes required painstaking, gene-by-gene searches. Combining computer science and biology, Princeton scientist Olga Troyanskaya, graduate student Chad Myers and other colleagues invented a method for quickly analyzing an entire genome -- all the genes contained in a cell -- and producing a reliable list of chromosome sections that have been either deleted or added.
"The problem is similar to finding typos in a very large book written in a language you don't fully understand," said Troyanskaya, an assistant professor in the Department of Computer Science and the Lewis-Sigler Institute for Integrative Genomics. "All you know are some general rules of grammar and syntax. It would take you years to do by hand, and it's even very hard with a computer."
Troyanskaya and Myers started with data from genomics tools that identify thousands of genes at once and show how actively they are being used. They used advanced statistical techniques to analyze this data and accurately detect deletions and additions -- some as small as four or five genes -- among tens of thousands of genes.
The achievement illustrates the value of the interdisciplinary environment fostered by the Lewis-Sigler Institute for Integrative Genomics, said Troyanskaya. "For this kind of problem you need people who understand computer science, statistics and biology," she said. "Neither side could do it alone."
Their findings will be published in an upcoming edition of the journal Bioinformatics and were posted to the journal's Web site July 29. Troyanskaya and Myers wrote the paper in collaboration with Lewis-Sigler fellow Maitreya Dunham and professor of electrical engineering Sun-Yuan Kung.
The researchers applied their technique to yeast cells as well as human breast cancer cells and found many previously unknown additions and deletions. The results support an idea proposed by some biologists that chromosome additions and deletions are more common than previously believed.
"If a cell really wants to change its behavior drastically -- if it is a cancer cell or something has changed in its environment -- the fastest way is just to amplify or delete a chunk of chromosome," said Troyanskaya. "We needed a way to identify these deletions and amplifications very accurately."