Identification, monitoring and treatment of disease and characterization of biological condition using gene expression profiles
A method provides an index that is indicative of the state of a subject, as to a biological condition, based on a sample from the subject. An embodiment of this method includes: deriving from the sample a profile data set, the profile data set including a plurality of members, each member being a quantitative measure of the amount of a distinct RNA or protein constituent in a panel of constituents selected so that measurement of the constituents enables evaluation of the biological condition; and in deriving the profile data set, achieving such measure for each constituent under measurement conditions that are substantially repeatable; and applying values from the profile data set to an index function that provides a mapping from an instance of a profile data set into a single-valued measure of biological condition, so as to produce an index pertinent to the biological condition of the subject.
1. A method of predicting change in a biological condition of a subject as a result of exposure to an agent, the method comprising:
a) producing a first index for a sample from the subject in the absence of the agent, the sample providing a source of RNAs comprising:
i) using amplification for quantitatively measuring the amount of RNA of at least two constituents from any one of Tables 1 through 12 from the sample from the subject, wherein a panel of constituents is selected so that measurement conditions of the constituents enables evaluation of said biological condition and wherein the measures of all constituents in the panel form a first profile data set, wherein said amplification for each constituent is under conditions that are (1) within a degree of repeatability of better than five percent; and (2) the efficiencies of amplification are within two percent;
ii) using amplification for quantitatively measuring the amount of RNA of all constituents in said panel wherein the measures of all constituents in the panel are from a relevant population of subjects and form a normative baseline profile data set; and
iii) applying values from the first profile data set to an index function derived using latent class modeling, thereby providing a single-valued measure of the biological condition so as to produce an index pertinent to the biological condition of the subject;
wherein the index function also uses data from the normative baseline profile data set,
b) producing a second index for a second sample from the subject in the presence of the agent, the second index based on the same panel of constituents; and
c) using the first and second indices to predict change in the biological condition of the subject as a result of exposure to the agent.
2. A method according to claim 1 , wherein the agent is a compound.
3. A method according to claim 2 , wherein the compound is therapeutic.