The present invention provides methods for enhanced detection of
biological response patterns. In one embodiment of the invention, genes
are grouped into basis genesets according to the co-regulation of their
expression. Expression of individual genes within a geneset is indicated
with a single gene expression value for the geneset by a projection
process. The expression values of genesets, rather than the expression of
individual genes, are then used as the basis for comparison and detection
of biological response with greatly enhanced sensitivity. In another
embodiment of the invention, biological responses are grouped according
to the similarity of their biological profile.The methods of the
invention have many useful applications, particularly in the fields of
drug development and discovery. For example, the methods of the invention
may be used to compare biological responses with greatly enhanced
sensitivity. The biological responses that may be compared according to
these methods include responses to single perturbations, such as a
biological response to a mutation or temperature change, as well as
graded perturbations such as titration with a particular drug. The
methods are also useful to identify cellular constituents, particularly
genes, associated with a particular type of biological response. Further,
the methods may also be used to identify perturbations, such as novel
drugs or mutations, which effect one or more particular genesets. The
methods may still further be used to remove experimental artifacts in
biological response data.