Determining if genetic mutations are a side effect of certain cancers rather than a cause will require further investigation, as will identifying which of the 118 genes that do not cycle in cancer cells are most significant.
These genes seem to be important, but we dont yet know which ones play key roles or might be targets for drug therapy, Simon said. We have narrowed down the field of candidates. Instead of looking at thousands of genes, now we can concentrate on about 100.
Using conventional techniques even to identify a full complement of human cell cycle genes has been problematic. Molecular biologists have found cell cycle genes in yeast, plants and mice, as well as in a human cancer cell line known as HeLa. But a study that purported to identify cell cycle genes in normal human cells proved flawed and invalid.
The problem that molecular biologists encountered in studying human cells has to do with the fact that the cell development must be arrested so that micro array technology can be used to measure which genes are expressed at each stage of the cell cycle. When the cells are released from arrest, Simon said, some dont resume cycling at all, while others resume at different intervals.
Why this is a problem in humans and not other species is not understood, Simon noted. But the result is that the cells and these studies require millions of them end up scattered among different stages of the cell cycle. Measurements of these unsynchronized cells are hopelessly noisy.
People said you couldnt solve this problem, Bar-Joseph said. But a computer science method called deconvolution, which is widely used in such fields as image processing and signal processing, proved effective in eliminating noise from the data.
In experiments, the team arrested and released cells in culture and then measured DNA content to determine which ones had stopped cyclin
|Contact: Byron Spice|
Carnegie Mellon University