Systems and methods for characterizing a biological conditions or agent using selected gene expression profiles

Abstract

Methods are provided for evaluating a biological condition of a subject using a calibrated profile data set derived from a data set having a plurality of members, each member being a quantitative measure of the amount of a subject's RNA or protein as distinct constituents in a panel of constituents. The biological condition may be a naturally occurring physiological state or may be responsive to treatment of the subject with one or more agents. Calibrated profile data sets may be used as a descriptive record for an agent.

We claim:  
     
         1 . A method, for evaluating a biological condition of a subject, based on a sample from the subject, the sample providing a source of RNAs, the method comprising: 
 deriving from the sample a first profile data set, the first profile dataset 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 enables evaluation of the biological condition wherein such measure for each constituent is obtained under measurement conditions that are substantially reproducible; and    producing a calibrated profile data set for the panel, wherein each member of the calibrated profile data set is a function of a corresponding member of the first profile data set and a corresponding member of a baseline profile data set for the panel, and wherein the baseline profile data set is related to the biological condition to be evaluated,    the calibrated profile data set being a comparison between the first profile data set and the baseline profile data set, thereby providing an evaluation of the biological condition of the subject.    
     
     
         2 . A method according to  claim 1 , wherein the measurement conditions are such that the coefficient of variation, on repeatedly obtaining such measure, is less than approximately 3 percent.  
     
     
         3 . A method according to  claim 1 , wherein the measurement conditions are such that the coefficient of variation, on repeatedly obtaining such measure, is less than approximately 2 percent.  
     
     
         4 . A method according to  claim 1 , wherein the baseline profile data set is derived from one or more other samples from the same subject taken under circumstances different from those of the sample.  
     
     
         5 . A method according to  claim 4 , wherein the circumstances are selected from the group consisting of (i) the time at which a given sample is taken, (ii) the site from which a given sample is taken, (iii) the biological condition of the subject when a given sample is taken.  
     
     
         6 . A method according to  claim 4 , wherein the one or more other samples are taken over an interval of time between an initial sample and the sample.  
     
     
         7 . A method according to  claim 4 , wherein the one or more other samples are taken over an interval of time that is at least twelve months between an initial sample and the sample.  
     
     
         8 . A method according to  claim 4 , wherein the one or more other samples are taken over an interval of time that is at least one month between an initial sample and the sample.  
     
     
         9 . A method according to  claim 1 , wherein the sample is derived from blood and the baseline profile data set is derived from tissue or body fluid of the subject other than blood.  
     
     
         10 . A method according to  claim 4 , wherein the baseline profile data set is derived from one or more other samples from the same subject, taken when the subject is in a biological condition different from that in which the subject was at the time the sample was taken, with respect to at least one of age, diet, medication, and environmental exposure.  
     
     
         11 . A method according to  claim 1 , wherein the baseline profile data set is derived from one or more other samples from one or more different subjects.  
     
     
         12 . A method according to  claim 11 , wherein the one or more different subjects have in common with the subject at least one of age group, gender, ethnicity, geographic location, diet, medical disorder, clinical indicator, medication, physical activity, body mass, and environmental exposure.  
     
     
         13 . A method according to  claim 12  wherein a clinical indicator has been used to assess biological condition of the one or more different subjects, further comprising: interpreting the calibrated profile data set in the context of at least one other clinical indicator  
     
     
         14 . A method according to  claim 13 , wherein the at least one other clinical indicator is selected from the group consisting of blood chemistry, urinalysis, X-ray, other chemical assays, and physical findings.  
     
     
         15 . A method according to  claim 1 , wherein the biological condition is a complex disease process, involving multiple genes, the disease being of a type involving at least one of inflammation, auto-immune disease, degenerative disease, allergy, vascular disease, ischemia, cancer, developmental disease, hormonal condition, aging and infectious diseases.  
     
     
         16 . A method according to  claim 15 , wherein the biological condition is one of arthritis, asthma, multiple sclerosis, and perimenopausal change.  
     
     
         17 . A method according to  claim 1 , wherein the subject is a living organism.  
     
     
         18 . A method according to  claim 17 , wherein the subject is a mammal.  
     
     
         19 . A method according to  claim 1 , wherein the sample is derived from one or more of body fluid and tissue.  
     
     
         20 . A method according to  claim 1 , wherein the sample is derived from blood.  
     
     
         21 . A method according to  claim 1 , wherein the sample is derived from one of a biopsy, a needle aspirate, a lavage specimen, a scraping, and a surgical specimen.  
     
     
         22 . A method according to  claim 1 , wherein the sample is derived from tissue or fluid of a type distinct from that with respect to which the condition is clinically manifested.  
     
     
         23 . A method according to  claim 1 , wherein the condition is a disease and the sample is derived from tissue or fluid of a type distinct from that which is a primary target of the disease.  
     
     
         24 . A method according to  claim 1 , wherein the function is other than a simple difference.  
     
     
         25 . A method according to  claim 24 , wherein the function is a second function of the ratio of the corresponding member of first profile data set to the corresponding member of the baseline profile data set.  
     
     
         26 . A method according to  claim 25 , wherein the function is a logarithmic function.  
     
     
         27 . A method according to  claim 25 , wherein each member of the calibrated profile data set has biological significance if it has a value differing by more than an amount D, where D=F(1.1)-F(0.9), and F is the second function.  
     
     
         28 . A method according to  claim 1 , wherein the biological condition concerns an organ and the panel of constituents enables measurement of the condition in relation to the organ.  
     
     
         29 . A method according to  claim 1 , wherein the biological condition concerns a system of the subject, the system selected from the group consisting of respiratory, vascular, nervous, metabolic, urinary, reproductive, structural, and immunological systems, and the panel of constituents enables measurement of the condition of the subject in relation to the system.  
     
     
         30 . A method according to  claim 1 , wherein the number of constituents in the panel is at least three but less than 100.  
     
     
         31 . A method according to  claim 1 , wherein the number of constituents in the panel is at least four but less than 100.  
     
     
         32 . A method according to  claim 1 , wherein the number of constituents in the panel is at least at least five but less than 100.  
     
     
         33 . A method according to  claim 1 , wherein the number of constituents in the panel is at least is at least six.  
     
     
         34 . A method according to  claim 1 , wherein the number of constituents in the panel is at least 4.  
     
     
         35 . A method according to  claim 1 , wherein the number of constituents in the panel is at least 3.  
     
     
         36 . A method according to  claim 1 , wherein the number of constituents in the panel is at least 2.  
     
     
         37 . A method according to  claim 1 , wherein deriving the first profile data set from the sample includes hybridizing the sample with a set of nucleic acid probes.  
     
     
         38 . A method according to  claim 37 , wherein the probes are attached to an insoluble matrix and the sample is applied to the matrix.  
     
     
         39 . A method according to  claim 1 , wherein obtaining the sample and quantifying the first profile data set are performed at a first location, and producing the calibrated profile data set includes using a network to access a database stored on a digital storage medium in a second location.  
     
     
         40 . A method according to  claim 39 , further comprising updating the database to reflect the first profile data set quantified from the sample.  
     
     
         41 . A method according to  claim 39 , wherein using a network includes accessing a global computer network.  
     
     
         42 . A method according to  claim 1 , wherein the quantitative measure is determined by amplification, and the measurement conditions are such that efficiencies of amplification for all constituents differ by less than approximately ten percent.  
     
     
         43 . A method according to  claim 1 , wherein the quantitative measure is determined by amplification, and the measurement conditions are such that efficiencies of amplification for all constituents differ by less than approximately 2 percent.  
     
     
         44 . A method according to  claim 1 , wherein the quantitative measure is determined by amplification, and the measurement conditions are such that efficiencies of amplification for all constituents differ by less than approximately 1 percent.  
     
     
         45 . A method according to  claim 1 , further comprising: 
 accessing a data in a condition database, the condition database having a plurality of records relating to a population of subjects, each record corresponding to a distinct instance of the calibrated profile data set; and    evaluating the first instance of the calibrated profile data set in relation to data in the condition database.    
     
     
         46 . A method according to  claim 44 , wherein accessing the condition database includes accessing the condition database over a network.  
     
     
         47 . A method according to  claim 46 , wherein the network is a global computer network.  
     
     
         48 . A method according to  claim 46 , further comprising supplementing the condition database based on data associated with the first instance of the calibrated profile data set.  
     
     
         49 . A method according to  claim 46 , wherein the biological condition concerns a system of the subject, the system selected from the group consisting of respiratory, vascular, nervous, metabolic, urinary, reproductive, structural, and immunological systems and the panel of constituents enables measurement of the condition of the subject in relation to the system.  
     
     
         50 . A method according to  claim 46 , wherein each record also references a characteristic of the population relative to the record, the characteristic being at least one of age group, gender, ethnicity, geographic location, diet, medical disorder, medication, physical activity, body mass, and environmental exposure.  
     
     
         51 . A method according to  claim 46 , wherein the characteristic includes a clinical indicator.  
     
     
         52 . A method according to  claim 51 , wherein the function is a logarithmic function.  
     
     
         53 . A method according to  claim 51 , wherein the graphical format is a bar graph for each member of the calibrated profile data set.  
     
     
         54 . A method according to  claim 1  wherein the biological condition to be evaluated relates to inflammation and the panel includes at least half of the constituents of the Inflammation Precision Panel of Table 1.  
     
     
         55 . A method according to  claim 54 , wherein the panel includes at least eighty percent of the constituents of the Inflammation Precision Panel of Table 1.  
     
     
         56 . A method according to  claim 1  wherein the biological condition to be evaluated relates to cell growth and differentiation and the panel includes at least half of the constituents of the Cell Growth and Differentiation Precision Panel of Table 2.  
     
     
         57 . A method according to  claim 56 , wherein the panel includes at least eighty percent of the constituents of the Cell Growth and Differentiation Precision Panel of Table 2.  
     
     
         58 . A method according to  claim 1  wherein the biological condition to be evaluated relates to metabolism and toxicity and the panel includes at least half of the constituents of the Liver Metabolism and Toxicity Precision Panel of Table 3.  
     
     
         59 . A method according to  claim 58 , wherein the panel includes at least eighty percent of the constituents of the Metabolism and Toxicity Precision Panel of Table 3.  
     
     
         60 . A method according to  claim 1  wherein the biological condition to be evaluated relates to skin response and the panel includes at least half of the constituents of the Skin Response Precision Panel.  
     
     
         61 . A method according to  claim 60 , wherein the panel includes at least eighty percent of the constituents of the Skin Response Precision Panel of Table 4.  
     
     
         62 . A method according to  claim 1  wherein the biological condition to be evaluated relates to the vascular system and the panel includes at least half of the constituents of the Vascular Precision Panel of Table 6.  
     
     
         63 . A method according to  claim 62 , wherein the panel includes at least eighty percent of the constituents of the Vascular Precision Panel of Table 6.  
     
     
         64 . A method according to  claim 1  wherein the biological condition to be evaluated relates to the prostate health and disease and the panel includes at least half of the constituents of the Prostate Precision Panel of Table 5.  
     
     
         65 . A method according to  claim 64 , wherein the panel includes at least eighty percent of the constituents of the Prostate Precision Panel of Table 5.  
     
     
         66 . A method according to  claim 1  wherein the biological condition to be evaluated relates to the prostate health and disease and the panel includes at least half of the constituents of the Prostate Precision Panel of Table 7.  
     
     
         67 . A method according to  claim 66 , wherein the panel includes at least eighty percent of the constituents of the Prostate Precision Panel of Table 7.