Abstract: Methods and apparatus to identify a potential toxicity of a therapy in a biological system are described. In one embodiment, a method uses a computer model that represents a set of biological processes of the biological system. The method includes executing the computer model to identify a first set of biological processes contributing to the occurrence of a toxic state of the biological system. The method also includes identifying a set of biological assays based on the first set of biological processes and testing the therapy in the set of biological assays to identify a second set of biological processes modified by the therapy. The method further includes identifying the potential toxicity of the therapy based on the second set of biological processes.

Abstract: The invention encompasses systems, methods, and apparatus for predicting and monitoring an individual's response to a therapeutic regimen. The invention includes multiple virtual patients, an associating subsystem operable to associate the subject with one or more of the virtual patients, and a simulation engine operable to apply one or more experimental protocols to the one or more virtual patients identified with the subject to generate a set of outputs.

Abstract: Methods and apparatus to identify a potential toxicity of a therapy in a biological system are described. In one embodiment, a method uses a computer model that represents a set of biological processes of the biological system. The method includes executing the computer model to identify a first set of biological processes contributing to the occurrence of a toxic state of the biological system. The method also includes identifying a set of biological assays based on the first set of biological processes and testing the therapy in the set of biological assays to identify a second set of biological processes modified by the therapy. The method further includes identifying the potential toxicity of the therapy based on the second set of biological processes.

Abstract: The present invention includes methods and apparatus for use in rapid testing for and prediction of a PPAR? response (i.e. a response similar to that of PPAR? agonists). The invention includes a PPAR? response signature comprising a set of twenty genes. The invention discloses methods whereby the differential expression of the genes of the PPAR? response signature may be used to predict whether a compound will induce a PPAR? response in a test subject.

Abstract: An apparatus and method for validating a computer model is described. In one embodiment, a computer-readable medium comprises instructions to associate a set of configurations of a computer model with a stimulus-response test, each configuration of the set of configurations representing a different model scenario, the stimulus-response test defining a modification to each configuration of the set of configurations. The computer-readable medium also comprises instructions to apply the stimulus-response test to the set of configurations to produce a simulated response for each configuration of the set of configurations and instructions to compare the simulated responses for the set of configurations with an expected response to the stimulus-response test.

Abstract: The invention also provides methods, apparatuses and reagents useful for predicting future atherosclerosis based on expression levels of genes selected from the set of 68 genes with differential expression in response to pioglitazone and rosiglitazone. The invention also discloses reagent sets and biomarkers for predicting progression of atherosclerosis induced by anti-diabetic therapy in a subject. In one particular embodiment the invention provides a method for predict whether a compound will induce atherosclerosis using gene expression data from sub-acute treatments.

Abstract: Apparatus and methods for assessing metabolic substrate utilization are described. In one embodiment, a processor-readable medium includes code to receive data indicative of a plasma glucose concentration, a plasma free fatty acid concentration, and a respiratory quotient of a subject. The processor-readable medium also includes code to calculate, based on the data, respective values of a set of metabolic parameters. The set of metabolic parameters includes a first metabolic parameter and a second metabolic parameter. The value of the first metabolic parameter is indicative of whether the subject has a predisposition towards oxidation of a first type of metabolic substrate or a second type of metabolic substrate, and the value of the second metabolic parameter is indicative of the subject's responsiveness to a change in availability of the first type of metabolic substrate or the second type of metabolic substrate.

Abstract: The invention discloses reagent sets and gene signatures for predicting onset of renal tubule injury in a subject. The invention also provides a necessary set of 186 genes useful for generating signatures of varying size and performance capable of predicting onset of renal tubule injury. The invention also provides methods, apparatuses and reagents useful for predicting future renal tubule injury based on expression levels of genes in the signatures. In one particular embodiment the invention provides a method for predict whether a compound will induce renal tubule injury using gene expression data from sub-acute treatments.

Abstract: The invention encompasses systems, methods, and apparatus for predicting clinical outcomes and monitoring an individual's response to a therapeutic regimen. The invention further encompasses methods for predicting cardiovascular risk based a genetic marker status and methods for modifying a computer to reflect genetic data and for incorporating genetic markers into a virtual population.

Abstract: An apparatus and method for validating a computer model is described. In one embodiment, a computer-readable medium comprises instructions to associate a set of configurations of a computer model with a stimulus-response test, each configuration of the set of configurations representing a different model scenario, the stimulus-response test defining a modification to each configuration of the set of configurations. The computer-readable medium also comprises instructions to apply the stimulus-response test to the set of configurations to produce a simulated response for each configuration of the set of configurations and instructions to compare the simulated responses for the set of configurations with an expected response to the stimulus-response test.

Abstract: Disclosed is a method for predicting the biological activity of a compound by the similarity of its drug signature score to the scores of a plurality of known drug signatures.

Abstract: The present invention relates to a mathematical and computer model of a joint. The model includes representation of the biological processes related to the synovial tissue and cartilage. In one embodiment, the model represents a human joint afflicted with rheumatoid arthritis.

Abstract: The present invention provides methods and compositions for use in rapid test or prediction of the propensity of a test compound to induce cholesterol reduction in a subject. The invention also includes a cholesterol reduction signature as well as the method of deriving such signature.

Abstract: The invention encompasses a novel method of treating an inflammatory disease, such as rheumatoid arthritis, and novel methods of identifying and screening for drugs useful in the treatment of inflammatory diseases, such as rheumatoid arthritis, and their clinical symptoms. The inventors have made the discovery that the activity of galectin-3, a ?-galactoside-binding lectin known to have an effect on some cancers, has a significant impact on the pathophysiology of rheumatoid arthritis. The symptoms of an inflammatory disease, such as rheumatoid arthritis, may be alleviated by administering a compound that inhibits the activity of galectin-3.

Abstract: The present invention provides methods and compositions for use in rapid test or prediction of the propensity of a test compound to induce cholestasis in a subject. The invention also includes a Cholestasis signature database as well as the method of deriving such database.

Abstract: The present invention relates generally to a mathematical and computer model of diabetes related disorders (e.g., human type 2 diabetes) within the framework of multiple macronutrient metabolism. The model includes a representation of complex physiological control mechanisms directing, for example, fat metabolism, protein metabolism and/or carbohydrate metabolism. In one embodiment, for example, the model can account for the interconversion between macronutrients, as well as their digestion, absorption, storage, mobilization, and adaptive utilization, as well as the endocrine control of these processes. In this embodiment, the model can simulate, for example, a heterogeneous group of diabetes related disorders, from insulin resistant to severe diabetic, and can predict the likely effects of therapeutic interventions.

Abstract: A method of conducting a sequence of linked simulation operations, utilizing a computer-based simulation model, commences with the performance of a first simulation operation to generate an output condition. A further simulation operation, which is defined to sequentially follow the first simulation operation, is then formed utilizing the simulation model. The second simulation operation at least partially and automatically inherits the output condition generated by the first simulation operation as an input condition. In this way, the second simulation operation commences with a configuration captured from a preceding simulation operation as an input condition. Multiple simulation operations may at least partially inherit a configuration from the first simulation operation.

Abstract: A method of conducting a sequence of linked simulation operations, utilizing a computer-based simulation model, commences with the performance of a first simulation operation to generate an output condition. A further simulation operation, which is defined to sequentially follow the first simulation operation, is then formed utilizing the simulation model. The second simulation operation at least partially and automatically inherits the output condition generated by the first simulation operation as an input condition. In this way, the second simulation operation commences with a configuration captured from a preceding simulation operation as an input condition. Multiple simulation operations may at least partially inherit a configuration from the first simulation operation.

Abstract: The invention encompasses novel methods of treating rheumatoid arthritis and its symptoms and novel methods of identifying and screening for drugs useful in the treatment of rheumatoid arthritis and its clinical symptoms. Targeted manipulation of a computer model of a human rheumatic joint provided the surprising result that decreasing the activity of FLIP, an inhibitor of apoptosis, by at least 25% has a significant impact on the pathophysiology of rheumatoid arthritis. Inhibition of the activity of FLIP by at least 25% is predicted to alleviate the symptoms of rheumatoid arthritis.

Abstract: The invention encompasses novel methods of treating rheumatoid arthritis and its symptoms and novel methods of identifying and screening for drugs useful in the treatment of rheumatoid arthritis and its clinical symptoms. Targeted manipulation of a computer model of a human rheumatic joint provided the surprising result that cross-linking soluble Fas-ligand (sFasL) has a significant impact on the pathophysiology of rheumatoid arthritis. The symptoms of rheumatoid arthritis may be alleviated by administering a sFasL-specific cross-linker.