IDENTIFICATION, MONITORING AND TREATMENT OF INFECTIOUS DISEASE AND CHARACTERIZATION OF INFLAMMATORY CONDITIONS RELATED TO INFECTIOUS DISEASE USING GENE EXPRESSION PROFILES
A method is provided in various embodiments for determining a profile data set for a subject with infectious disease or inflammatory conditions related to infectious disease based on a sample from the subject, wherein the sample provides a source of RNAs. The method includes using amplification for measuring the amount of RNA corresponding to at least 2 constituents from Table 1. The profile data set comprises the measure of each constituent, and amplification is performed under measurement conditions that are substantially repeatable.
1 . A method for determining a profile data set for a subject with infectious disease or inflammatory conditions related to infectious disease based on a sample from the subject, the sample providing a source of RNAs, the method comprising:
using amplification for measuring the amount of RNA corresponding to at least 2 constituents from Table I and
arriving at a measure of each constituent,
wherein the profile data set comprises the measure of each constituent and wherein amplification is performed under measurement conditions that are substantially repeatable.
2 - 3 . (canceled)
4 . The method for determining a profile data set according to claim 1 , wherein the measurement conditions that are substantially repeatable are within a degree of repeatability of better than five percent.
5 . The method for determining a profile data set according to claim 1 , wherein the measurement conditions that are substantially repeatable are within a degree of repeatability of better than three percent.
6 . The method for determining a profile data set according to claim 1 , wherein efficiencies of amplification for all constituents are substantially similar.
7 . The method for determining a profile data set according to claim 6 , wherein the efficiency of amplification for all constituents is within two percent.
8 . The method for determining a profile data set according to claim 6 , wherein the efficiency of amplification for all constituents is less than one percent.
9 . The method according to claim 1 wherein the sample is selected from the group consisting of blood, a blood fraction, body fluid, a population of cells and tissue from the subject.
10 . A method of characterizing infectious disease or inflammatory conditions related to infectious disease in a subject, based on a sample from the subject, the sample providing a source of RNAs, the method comprising:
assessing a profile data set of a plurality of members, each member being a quantitative measure of the amount of a distinct RNA constituent in a panel of constituents selected so that measurement of the constituents enables characterization of the presumptive signs of a systemic infection, wherein such measure for each constituent is obtained under measurement conditions that are substantially repeatable.
11 . The method according to claim 10 , wherein the subject has presumptive signs of a systemic infection including at least one of: elevated white blood cell count, elevated temperature, elevated heart rate, and elevated or reduced blood pressure, relative to medical standards.
12 . The method according to claim 10 , wherein the subject has presumptive signs of a systemic infection that are related to inflammatory conditions arising from at least one of: blunt or penetrating trauma, surgery, endocarditis, urinary tract infection, pneumonia, or dental or gynecological examinations or treatments.
13 . The method for characterizing infectious disease or inflammatory conditions related to infectious disease in a subject according to claim 10 , wherein assessing further comprises:
comparing the profile data set to a baseline profile data set for the panel, wherein the baseline profile data set is related to the infectious disease or inflammatory conditions related to infectious disease to be characterized.
14 . The method for characterizing infectious disease or inflammatory conditions related to infectious disease in a subject according to claim 10 , wherein efficiencies of amplification for all constituents are substantially similar.
15 . The method according claim 10 , wherein the infectious disease or inflammatory conditions related to infectious disease are from a microbial infection.
16 - 21 . (canceled)
22 . The method according to claim 10 , wherein the infectious disease or inflammatory conditions related to infectious disease are from septicemia due to any class of microbe.
23 . The method according to claim 10 , wherein the infectious disease or inflammatory conditions related to infectious disease are with respect to a localized tissue of the subject and the sample is derived from a tissue of fluid of a type distinct from that of the localized tissue.
24 - 220 . (canceled)
221 . A method of providing an index that is indicative of an inflammatory condition of a subject with presumptive signs of a systemic infection, based on a first sample from the subject, the first sample providing a source of RNAs, the method comprising:
deriving from the first 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 constituent in a panel of constituents selected so that measurement of the constituents is indicative of the inflammatory condition, the panel including at least two of the constituents of the Gene Expression Panel of Table 1; and in deriving the profile data set,
achieving such measure for each constituent under measurement conditions that are substantially repeatable;
applying at least one measure from the profile data set to an index function that provides a mapping from at least one measure of the profile data set into at least one measure of the inflammatory condition, so as to produce an index pertinent to the inflammatory condition of the sample;
wherein the index function uses data from a baseline profile data set for the panel, each member of the baseline data set being a normative measure, determined with respect to a relevant set of subjects, of the amount of one of the constituents in the panel, wherein the baseline data set is related to the inflammatory condition to be evaluated.
222 - 225 . (canceled)
226 . The method of providing an index according to claim 221 , wherein the index function has 4 components including disease status, disease severity, or disease course.
227 . The method of providing an index according to claim 221 , wherein the index function has 5 components including disease status, disease severity, or disease course.
228 . The method of providing an index according to claim 221 , wherein the index function is constructed as a linear sum of terms having the form:
I=ΣCiMiP ( i ),
wherein I is the index, Mi is the value of the member i of the profile data set, Ci is a constant, and P(i) is a power to which Mi is raised, the sum being formed for all integral values of i up to the number of members in the data set.
229 . The method of providing an index according to claim 228 , wherein the values Ci and P(i) are determined using statistical techniques, such as latent class modeling, to correlate data, including clinical, experimentally derived, and any other data pertinent to the presumptive signs of a systemic infection.
230 - 262 . (canceled)