Systems and methods for characterizing a biological condition 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 affected by a first agent based on a first sample obtained from a target population of cells to which the first agent has been administered, the first sample providing a source of RNAs, the method comprising: 
 deriving from the first sample a first profile data set, the first 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 affected by the first agent, wherein such measure for each constituent is obtained under measurement conditions that are substantially similar; 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 first baseline profile data set for the panel, and wherein the first baseline profile is related to the biological condition to be evaluated affected by the first agent,    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 affected by the agent.    
     
     
         4 . 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.  
     
     
         5 . 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.  
     
     
         6 . A method according to  claim 1 , wherein the first sample is obtained from blood and the baseline profile data set is derived from one or more other samples obtained from tissue or body fluid of the subject other than blood.  
     
     
         7 . A method according to  claim 1 , wherein the baseline profile data set is derived from one or more other samples obtained from the same population of cells under circumstances different from those of the first sample.  
     
     
         8 . A method according to  claim 7 , wherein the circumstances are selected from the group consisting of (i) the time at which a given sample is obtained and (ii) the biological condition of the population when a given sample is obtained.  
     
     
         9 . A method according to  claim 10 , wherein the one or more other samples are obtained over an interval of time between the obtaining of the first sample and the obtaining of the one or more other samples.  
     
     
         10 . A method according to  claim 7 , wherein the one or more other samples are obtained over an interval of time that is at least twelve months between the obtaining of the first sample and the obtaining of the one or more other samples.  
     
     
         11 . A method according to  claim 7 , wherein the one or more other samples are obtained over an interval of time that is at least one month between the obtaining of the first sample and the obtaining of the one or more other samples.  
     
     
         12 . A method according to  claim 7 , wherein the first sample is derived from blood and the one or more other samples for the baseline profile data set are derived from tissue or body fluid of the subject other than blood.  
     
     
         13 . A method according to  claim 8 , wherein the baseline profile data set is derived from one or more other samples of the same population associated with a common subject, the one or more other samples 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.  
     
     
         14 . A method according to  claim 1 , wherein the baseline profile data set is derived from one or more other samples from one or more cell populations associated with different subjects.  
     
     
         15 . A method according to  claim 14 , wherein the 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.  
     
     
         16 . A method according to  claim 15 , wherein a clinical indicator has been used to assess biological condition for the different subjects, further comprising: interpreting the calibrated profile data set in the context of at least one other clinical indicator.  
     
     
         17 . A method according to  claim 16 , 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.  
     
     
         18 . 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.  
     
     
         19 . A method according to  claim 18 , wherein the biological condition is one of arthritis, asthma, multiple sclerosis, and premenopausal change.  
     
     
         20 . A method according to  claim 1 , wherein the population of cells is human cells.  
     
     
         21 . A method according to  claim 1 , wherein the population of cells is mammalian cells.  
     
     
         22 . A method according to  claim 1 , wherein the sample is derived from one or more of body fluid and tissue.  
     
     
         23 . A method according to  claim 1 , wherein the sample is derived from blood.  
     
     
         24 . 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.  
     
     
         25 . 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.  
     
     
         26 . 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.  
     
     
         27 . A method according to  claim 1 , wherein the function is other than a simple difference.  
     
     
         28 . A method according to  claim 27 , 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.  
     
     
         29 . A method according to  claim 28 , wherein the function is a logarithmic function.  
     
     
         30 . A method according to  claim 28 , 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.  
     
     
         31 . 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.  
     
     
         32 . A method according to  claim 1 , wherein the population of cells is derived from a subject and 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.  
     
     
         33 . A method according to  claim 32  and the panel includes at least half of the constituents of the Inflammation Precision Panel.  
     
     
         34 . A method according to  claim 32  and the panel includes at least eighty percent of the constituents of the Inflammation Precision Panel.  
     
     
         35 . A method according to  claim 32  and the panel includes at least half of the constituents of the Cell Growth and Differentiation Precision Panel.  
     
     
         36 . A method according to  claim 32  and the panel includes at least eighty percent of the constituents of the Cell Growth and Differentiation Precision Panel.  
     
     
         37 . A method according to  claim 32  and the panel includes at least half of the constituents of a Metabolism and Toxicity Precision Panel.  
     
     
         38 . A method according to  claim 32  and the panel includes at least eighty percent of the constituents of a Metabolism and Toxicity Precision Panel.  
     
     
         39 . A method according to  claim 1 , wherein the number of constituents in the panel is at least three but less than 100.  
     
     
         40 . A method according to  claim 1 , wherein the number of constituents in the panel is at least four but less than 100.  
     
     
         41 . A method according to  claim 1 , wherein the number of constituents in the panel is at least at least five but less than 100.  
     
     
         42 . A method according to  claim 1 , wherein the number of constituents in the panel is at least is at least six.  
     
     
         43 . A method according to  claim 1 , wherein the number of constituents in the panel is at least 4.  
     
     
         44 . A method according to  claim 1 , wherein the number of constituents in the panel is at least 3.  
     
     
         45 . A method according to  claim 1 , wherein the number of constituents in the panel is at least 2.  
     
     
         46 . A method according to  claim 1 , wherein the agent is selected from the group consisting of a drug, a mixture of compounds, a functional food, a nutraceutical, a therapeutic agent, an allergen, and a toxin.  
     
     
         47 . 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.  
     
     
         48 . A method according to  claim 47 , wherein the probes are attached to an insoluble matrix and the sample is applied to the matrix.  
     
     
         49 . A method according to  claim 1 , wherein evaluating the condition affected by the agent includes evaluating the interaction of the agent with a second agent administered to the population of cells.  
     
     
         50 . A method according to  claim 49 , wherein the interaction is neutral.  
     
     
         51 . A method according to  claim 49 , wherein the interaction is interference.  
     
     
         52 . A method according to  claim 49 , wherein the interaction is cumulative.  
     
     
         53 . A method according to  claim 49 , wherein the interaction is synergistic.  
     
     
         54 . A method according to  claim 49 , wherein the first agent is a pharmaceutical.  
     
     
         55 . A method according to  claim 1 , further comprising evaluating the effect on a biological condition by a first agent in relation to the effect on the biological condition by a second agent based on a second sample obtained from a second target population of cells to which the second agent has been administered, the method further comprising: 
 deriving a second profile data set from the second sample, the second 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 affected by the second agent, wherein such measure for each constituent is obtained under measurement conditions that are substantially similar; and    producing a second calibrated data set for the panel, wherein each member of the second calibrated profile data set is a function of a corresponding member of the second profile data set and a corresponding member of a second baseline profile data set for the panel, and wherein the second baseline profile data set is related to the biological condition to be evaluated affected by the second agent,    the first and second calibrated profile data sets being comparisons between the first and second profile data sets and the first and second baseline data sets, respectively, thereby providing an evaluation of the effect by the first agent on the biological condition in relation to the effect by the second agent.    
     
     
         56 . A method according to  claim 55 , wherein the first agent is a drug and the second agent is a complex mixture.  
     
     
         57 . A method according to  claim 55 , wherein the first agent is a drug and the second agent is a nutraceutical.  
     
     
         58 . A method according to  claim 1 , wherein deriving the first profile data set is performed at a first location, and producing the calibrated profile data set is performed at a second location and includes using a network to access a database stored on a digital storage medium.  
     
     
         59 . A method according to  claim 58 , further comprising updating the database to reflect the first profile data set derived from the sample.  
     
     
         60 . A method according to  claim 58 , wherein using a network includes accessing a global computer network.  
     
     
         61 . 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.  
     
     
         62 . 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.  
     
     
         63 . 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.  
     
     
         64 . 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.    
     
     
         65 . A method according to  claim 64 , wherein accessing the condition database includes accessing the condition database over a network.  
     
     
         66 . A method according to  claim 65 , wherein the network is a global computer network.  
     
     
         67 . A method according to  claim 65 , further comprising supplementing the condition database based on data associated with the first instance of the calibrated profile data set.  
     
     
         68 . A method according to  claim 65 , 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.  
     
     
         69 . A method according to  claim 65 , 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.  
     
     
         70 . A method according to  claim 65 , wherein the characteristic includes a clinical indicator.  
     
     
         71 . A method according to  claim 70 , wherein the function is a logarithmic function.  
     
     
         72 . A method according to  claim 70 , wherein the graphical format is a bar graph for each member of the calibrated profile data set.  
     
     
         73 . 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.  
     
     
         74 . A method according to  claim 73 , wherein the panel includes at least eighty percent of the constituents of the Inflammation Precision Panel of Table 1.  
     
     
         75 . 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.  
     
     
         76 . A method according to  claim 75 , wherein the panel includes at least eighty percent of the constituents of the Cell Growth and Differentiation Precision Panel of Table 2.  
     
     
         77 . 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.  
     
     
         78 . A method according to  claim 77 , wherein the panel includes at least eighty percent of the constituents of the Metabolism and Toxicity Precision Panel of Table 3.  
     
     
         79 . 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.  
     
     
         80 . A method according to  claim 79 , wherein the panel includes at least eighty percent of the constituents of the Skin Response Precision Panel of Table 4.  
     
     
         81 . 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.  
     
     
         82 . A method according to  claim 81 , wherein the panel includes at least eighty percent of the constituents of the Vascular Precision Panel of Table 6.  
     
     
         83 . 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.  
     
     
         84 . A method according to  claim 83 , wherein the panel includes at least eighty percent of the constituents of the Prostate Precision Panel of Table 5.  
     
     
         85 . 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.  
     
     
         86 . A method according to  claim 85 , wherein the panel includes at least eighty percent of the constituents of the Prostate Precision Panel of Table 7.