Gene Expression Profiling - Use in Hypothesis Generation and Testing

Use in Hypothesis Generation and Testing

Sometimes, a scientist already has an idea what is going on, a hypothesis, and he or she performs an expression profiling experiment with the idea of potentially disproving this hypothesis. In other words, the scientist is making a specific prediction about levels of expression that could turn out to be false.

More commonly, expression profiling takes place before enough is known about how genes interact with experimental conditions for a testable hypothesis to exist. With no hypothesis, there is nothing to disprove, but expression profiling can help to identify a candidate hypothesis for future experiments. Most early expression profiling experiments, and many current ones, have this form which is known as class discovery. A popular approach to class discovery involves grouping similar genes or samples together using k-means or hierarchical clustering. The figure above represents the output of a two dimensional cluster, in which similar samples (rows, above) and similar gene probes (columns) were organized so that they would lie close together. The simplest form of class discovery would be to list all the genes that changed by more than a certain amount between two experimental conditions.

Class prediction is more difficult than class discovery, but it allows one to answer questions of direct clinical significance such as, given this profile, what is the probability that this patient will respond to this drug? This requires many examples of profiles that responded and did not respond, as well as cross-validation techniques to discriminate between them.