Methods for determining therapeutic index from gene expression profiles

A method for monitoring a therapy for a patient, said therapy comprising administering a drug to said patient, said method comprising:

• (a) decomposing a drug response profile into one or a combination of pathway response profiles, wherein the drug response profile comprises measurements of a plurality of cellular constituents in cells of said patient in response to administration of said drug over a plurality of levels of drug exposure, and each said pathway response profile comprises measurements of a plurality of cellular constituents at a plurality of levels of perturbation to a biological pathway;
• and
• (b) comparing, among said one or a combination of pathway response profiles, the pathway response profiles for the one or more biological pathways associated with therapeutic effects of the drug with the pathway response profiles for the one or more biological pathways that are associated with one or more non-therapeutic effects of the drug, thereby comparing activity of said drug on its target pathway (Dtarget) and at least one off-target pathway (Doff-target) and monitoring said therapy in said patient.

A method for monitoring a therapy for a patient, said therapy comprising administering a drug to said patient, said method comprising decomposing a drug response profile into one or a combination of pathway response profiles, wherein said drug response profile comprises measurements of a plurality of cellular constituents in cells of said patient in response to administration of said drug over a plurality of levels of drug dosage, and each said pathway response profile comprises measurements of a plurality of cellular constituents at a plurality of levels of perturbation to a biological pathway, thereby monitoring said therapy.