Abstract: Methods comprising an integrated, multiscale artificial intelligence-based system that reconstructs drug-specific pharmacogenomic networks and their constituent functional sub-networks are described. The system uses features of the functional topology of the three-dimensional architecture of drug-modulated spatial contacts in chromatin space. Discovery of a drug pharmacogenomic network is made through the selection of candidate SNPs by imputation, determination of the predicted causality of the SNPs using machine learning and deep learning, use of the causal SNPs to probe the spatial genome as determined by chromosome conformation capture analysis, combining targeted genes controlled by the same cell and tissue-specific enhancers, and reconstruction of the pharmacogenomic network using diverse data sources and metrics based on the results of genome-wide association studies.

Abstract: Methods comprising an integrated, multiscale artificial intelligence-based system that reconstructs drug-specific pharmacogenomic networks and their constituent functional sub-networks are described. The system uses features of the functional topology of the three-dimensional architecture of drug-modulated spatial contacts in chromatin space. Discovery of a drug pharmacogenomic network is made through the selection of candidate SNPs by imputation, determination of the predicted causality of the SNPs using machine learning and deep learning, use of the causal SNPs to probe the spatial genome as determined by chromosome conformation capture analysis, combining targeted genes controlled by the same cell and tissue-specific enhancers, and reconstruction of the pharmacogenomic network using diverse data sources and metrics based on the results of genome-wide association studies.

Abstract: The ability to automate the processes of specimen collection, image acquisition, data pre-processing, computation of derived biomarkers, modeling, classification and analysis can significantly impact clinical decision-making and fundamental investigation of cell deformation. This disclosure combine 3D cell nuclear shape modeling by robust smooth surface reconstruction and extraction of shape morphometry measure into a highly parallel pipeline workflow protocol for end-to-end morphological analysis of thousands of nuclei and nucleoli in 3D. This approach allows efficient and informative evaluation of cell shapes in the imaging data and represents a reproducible technique that can be validated, modified, and repurposed by the biomedical community. This facilitates result reproducibility, collaborative method validation, and broad knowledge dissemination.

Abstract: For patients who exhibit or may exhibit primary or comorbid disease, pharmacological phenotypes may be predicted through the collection of panomic data over a period of time. A machine learning engine may generate a statistical model based on training data from training patients to predict pharmacological phenotypes, including drug response and dosing, drug adverse events, disease and comorbid disease risk, drug-gene, drug-drug, and polypharmacy interactions. Then the model may be applied to data for new patients to predict their pharmacological phenotypes, and enable decision making in clinical and research contexts, including drug selection and dosage, changes in drug regimens, polypharmacy optimization, monitoring, etc., to benefit from additional predictive power, resulting in adverse event and substance abuse avoidance, improved drug response, better patient outcomes, lower treatment costs, public health benefits, and increases in the effectiveness of research in pharmacology and other biomedical fields.

Abstract: Methods comprising an integrated, multiscale artificial intelligence-based system that reconstructs drug-specific pharmacogenomic networks and their constituent functional sub-networks are described. The system uses features of the functional topology of the three-dimensional architecture of drug-modulated spatial contacts in chromatin space. Discovery of a drug pharmacogenomic network is made through the selection of candidate SNPs by imputation, determination of the predicted causality of the SNPs using machine learning and deep learning, use of the causal SNPs to probe the spatial genome as determined by chromosome conformation capture analysis, combining targeted genes controlled by the same cell and tissue-specific enhancers, and reconstruction of the pharmacogenomic network using diverse data sources and metrics based on the results of genome-wide association studies.

Abstract: Methods for identifying patients diagnosed with treatment resistant or refractory depression, pain or other clinical indications who are eligible to receive N-methyl-D-aspartate receptor antagonist, glycine receptor beta (GLRB) modulator, or ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-based therapies to include determining the appropriate medication, an optimal dose for each patient, and determining which patients are not eligible to receive the therapy. The pharmacogenomic clinical decision support assays include targeted single nucleotide polymorphisms and clinical values or a combination of targeted single nucleotide polymorphisms, targeted ketamine-specific expansion and contraction of topologically associated domains, and clinical values. The methods described herein allow for a more effective determination of which patients will experience drug efficacy and which patients will experience adverse drug events.

Abstract: For patients who exhibit or may exhibit primary or comorbid disease, pharmacological phenotypes may be predicted through the collection of panomic data over a period of time. A machine learning engine may generate a statistical model based on training data from training patients to predict pharmacological phenotypes, including drug response and dosing, drug adverse events, disease and comorbid disease risk, drug-gene, drug-drug, and polypharmacy interactions. Then the model may be applied to data for new patients to predict their pharmacological phenotypes, and enable decision making in clinical and research contexts, including drug selection and dosage, changes in drug regimens, polypharmacy optimization, monitoring, etc., to benefit from additional predictive power, resulting in adverse event and substance abuse avoidance, improved drug response, better patient outcomes, lower treatment costs, public health benefits, and increases in the effectiveness of research in pharmacology and other biomedical fields.

Abstract: For patients who exhibit or may exhibit primary or comorbid disease, pharmacological phenotypes may be predicted through the collection of panomic data over a period of time. A machine learning engine may generate a statistical model based on training data from training patients to predict pharmacological phenotypes, including drug response and dosing, drug adverse events, disease and comorbid disease risk, drug-gene, drug-drug, and polypharmacy interactions. Then the model may be applied to data for new patients to predict their pharmacological phenotypes, and enable decision making in clinical and research contexts, including drug selection and dosage, changes in drug regimens, polypharmacy optimization, monitoring, etc., to benefit from additional predictive power, resulting in adverse event and substance abuse avoidance, improved drug response, better patient outcomes, lower treatment costs, public health benefits, and increases in the effectiveness of research in pharmacology and other biomedical fields.

Abstract: The ability to automate the processes of specimen collection, image acquisition, data pre-processing, computation of derived biomarkers, modeling, classification and analysis can significantly impact clinical decision-making and fundamental investigation of cell deformation. This disclosure combine 3D cell nuclear shape modeling by robust smooth surface reconstruction and extraction of shape morphometry measure into a highly parallel pipeline workflow protocol for end-to-end morphological analysis of thousands of nuclei and nucleoli in 3D. This approach allows efficient and informative evaluation of cell shapes in the imaging data and represents a reproducible technique that can be validated, modified, and repurposed by the biomedical community. This facilitates result reproducibility, collaborative method validation, and broad knowledge dissemination.

Abstract: For patients who exhibit or may exhibit primary or comorbid disease, pharmacological phenotypes may be predicted through the collection of panomic data over a period of time. A machine learning engine may generate a statistical model based on training data from training patients to predict pharmacological phenotypes, including drug response and dosing, drug adverse events, disease and comorbid disease risk, drug-gene, drug-drug, and polypharmacy interactions. Then the model may be applied to data for new patients to predict their pharmacological phenotypes, and enable decision making in clinical and research contexts, including drug selection and dosage, changes in drug regimens, polypharmacy optimization, monitoring, etc., to benefit from additional predictive power, resulting in adverse event and substance abuse avoidance, improved drug response, better patient outcomes, lower treatment costs, public health benefits, and increases in the effectiveness of research in pharmacology and other biomedical fields.

Abstract: For patients who exhibit or may exhibit primary or comorbid disease, pharmacological phenotypes may be predicted through the collection of panomic, physiomic, environmental, sociomic, demographic, and outcome phenotype data over a period of time. A machine learning engine may generate a statistical model based on training data from training patients to predict pharmacological phenotypes, including drug response and dosing, drug adverse events, disease and comorbid disease risk, drug-gene, drug-drug, and polypharmacy interactions. Then the model may be applied to data for new patients to predict their pharmacological phenotypes, and enable decision making in clinical and research contexts, including drug selection and dosage, changes in drug regimens, polypharmacy optimization, monitoring, etc.

Abstract: For patients who exhibit or may exhibit primary or comorbid disease, pharmacological phenotypes may be predicted through the collection of panomic, physiomic, environmental, sociomic, demographic, and outcome phenotype data over a period of time. A machine learning engine may generate a statistical model based on training data from training patients to predict pharmacological phenotypes, including drug response and dosing, drug adverse events, disease and comorbid disease risk, drug-gene, drug-drug, and polypharmacy interactions. Then the model may be applied to data for new patients to predict their pharmacological phenotypes, and enable decision making in clinical and research contexts, including drug selection and dosage, changes in drug regimens, polypharmacy optimization, monitoring, etc.