Abstract: The present disclosure relates to systems and methods for predicting response to cancer therapy, genes useful for predicting the sensitivity of a cancer to an anti-cancer therapy, and methods of treating such cancer.

Abstract: An agent which increases pyrimidine to purine ration in a cell without decreasing pyrimidine synthesis for use in a method of treating a solid tumor in a subject in need thereof, optionally in combination with an immune-modulating drug.

Abstract: Provided herein are methods of identifying gene expression levels in specific cell types based on bulk gene expression levels measured in tissue samples comprising a plurality of cell types.

Abstract: A pharmaceutical composition includes an active agent capable of reducing dihydroorotate dehydrogenase (DHODH) enzyme activity in the central nervous system (CNS), and a pyrimidine nucleobase or an intermediate in the de novo synthesis thereof. A method for treating a disease or disorder associated with cortico-hippocampal hyperactivity in a subject in need thereof, or for preventing or delaying onset of the disease or disorder in a subject diagnosed as suffering from an elevated cortico-hippocampal activity or being at genetic risk for developing the disease or disorder. The method includes administering to the subject a therapeutically effective amount of the pharmaceutical composition above.

Abstract: The present invention provides pharmaceutical compositions and methods for preventing, delaying onset of, or treating diseases or disorders associated with cortico-hippocampal hyperactivity such as epilepsy, using an active agent capable of reducing dihydroorotate dehydrogenase (DHODH) enzyme activity in the central nervous system, optionally together with a pyrimidine nucleobase or an intermediate in the de novo synthesis thereof.

Abstract: The present invention provides pharmaceutical compositions and methods for preventing, delaying onset of, or treating diseases or disorders associated with cortico-hippocampal hyperactivity such as epilepsy, using an active agent capable of reducing dihydroorotate dehydrogenase (DHODH) enzyme activity in the central nervous system, optionally together with a pyrimidine nucleobase or an intermediate in the de novo synthesis thereof.

Abstract: The disclosure comprises methods for predicting survival rates in subjects or populations of subject affected by a disease or disorder. The disclosure relates to methods of predicting the likely effect of and/or likely resistance developed from a treatments or combination of treatments. Software so execute the steps disclosed here and computer-implemented methods are also disclosed.

Abstract: Systems and methods for identifying synthetic lethal (SL) and synthetic dosage lethal (SDL) interactions and networks are provided. Further provided are methods for predicting cancer gene essentiality, drug efficacy and survival of cancer patients using data-driven identification of synthetic lethality in cancer are provided. Novel drug candidates and drug combinations for use in cancer therapy and method for prioritizing existing cancer therapies are also provided.

Abstract: Systems and methods for identifying clinically relevant Synthetic Lethal interactions SLi by analyzing large and diverse cohorts of clinically relevant cancer data, utilizing a data driven approach, termed SLICK, are provided. Further provided are system and methods of utilizing SLICK to uncover therapeutic possibilities in cancer.

Abstract: A method for creating a metabolic map of metabolic reactions by selecting metabolic reactions active in cancer cells. A core set of metabolic reactions occurring in the cancer cells is designated. For each permutation, whether inhibition of the k-th non-core reaction together with inhibition of all previously deleted non-core reactions results in inhibition of any of the core reactions or results in inhibition of the flux of biomass metabolites to biomass is determined. If inhibition of the k-th non-core reaction and inhibition of all previously deleted non-core reactions does not result in inhibition of any core reactions and does not result in inhibition of the flux of biomass metabolites to biomass, then the k-th non-core reaction is deleted from the set of non-core reactions. The number of permutations for which the k-th non-core reaction is not deleted is determined and a metabolic map is then created based on that number.

Abstract: Systems and methods for identifying synthetic lethal (SL) and synthetic dosage lethal (SDL) interactions and networks are provided. Further provided are methods for predicting cancer gene essentiality, drug efficacy and survival of cancer patients using data-driven identification of synthetic lethality in cancer are provided. Novel drug candidates and drug combinations for use in cancer therapy and method for prioritizing existing cancer therapies are also provided.

Abstract: A processor implemented method for personalized metabolic modeling starting from a generic metabolic model. For each reaction Ri in the generic metabolic model, a correlation ?(i) between the expression level of the reaction and the level of a quantifiable phenotype in a population of cells is calculated. A set of highly correlated reactions is identified. An expression matrix, Exp-matrix, is then calculated which is used to generate the personalized metabolic model.

Abstract: A searchable protein database is disclosed. The protein database comprises a plurality of entries, each entry having a sufficiently short predicting sequence and a protein classifier corresponding to the predicting sequence. An unclassified protein sequence can be classifiable by the database via searching therein for a motif of amino acids matching a predicting sequence of the database, thereby attributing to the unclassified protein a protein classifier.

Abstract: A computer implemented method for identifying genetic or environmental perturbations that induce a transformation from a source state of an individual to a target state. A flux description of reactions is calculated in the source state and a statistical test is performed on the gene expression levels of the source state versus the target state, to generate a P-value for each on the plurality of genes. Then, for each reaction the flux of the reaction in the source state is fixed and a solution for all of the fluxes that minimize an objective function is found. These perturbations are ranked by the extent by which the perturbation caused a transformation of the source state towards the target state.

Abstract: A method for creating a metabolic map of metabolic reactions by selecting metabolic reactions active in cancer cells. A core set of metabolic reactions occurring in the cancer cells is designated. For each permutation, whether inhibition of the k-th non-core reaction together with inhibition of all previously deleted non-core reactions results in inhibition of any of the core reactions or results in inhibition of the flux of biomass metabolites to biomass is determined. If inhibition of the k-th non-core reaction and inhibition of all previously deleted non-core reactions does not result in inhibition of any core reactions and does not result in inhibition of the flux of biomass metabolites to biomass, then the k-th non-core reaction is deleted from the set of non-core reactions. The number of permutations for which the k-th non-core reaction is not deleted is determined and a metabolic map is then created based on that number.

Abstract: A method and system for scheduling events into a set of opportunities is presented. The method includes 1) dividing a path of an image acquisition device so that there is at least a first portion and a second portion at any given moment, wherein each of the first portion and the second portion includes at least one state and the first portion includes a null state in which no image is taken; 2) combining each state in the first portion with at least one state in the second portion one by one to generate a series of updated sequences; and 3) selecting at least one of the updated sequences based on a merit value associated with each of the updated sequences. The invention uses only two groups out of all the relevant opportunities for most calculations, and is especially applicable to situations like satellite pass scheduling.

Abstract: A method of generalizing a dataset having a plurality of sequences defined over a lexicon of tokens is provided. The method comprises: searching over the dataset for similarity sets, where each similarity set comprises a plurality of segments of size L having L?S common tokens and S uncommon tokens; and defining a plurality of equivalence classes corresponding to uncommon tokens of at least one similarity set. The method may further comprise a step in which a plurality of significant patterns are extracted, where each significant pattern corresponds to a most significant partial overlap between one sequence of the dataset and other sequences of the dataset. In one embodiment, a generalized dataset represented by a graph or a forest is constructed, and can be realized as a context-free grammar. The graph or forest can be used for generating sequences and/or testing grammatical structures.

Abstract: Apparatus for analysis of a complex system comprising elements to determine the effective elements of a system in carrying out a given task, the apparatus comprising: a sampler for carrying out successive silencing operations comprising silencing elements and combinations of elements of the system and measuring results of the given task, a predictor for providing predictions for predicting results for the given task for further element silencing combinations, and a contributions calculator for using said measured results and said predicted results to generate Shapley value predictions for said elements as indicators of an effectiveness of a respective element in carrying out the given task.

Abstract: Apparatus for analysis of a complex system comprising elements to determine the effective elements of a system in carrying out a given task, the apparatus comprising: a sampler for carrying out successive silencing operations comprising silencing elements and combinations of elements of the system and measuring results of the given task, a predictor for providing predictions for predicting results for the given task for further element silencing combinations, and a contributions calculator for using said measured results and said predicted results to generate Shapley value predictions for said elements as indicators of an effectiveness of a respective element in carrying out the given task.

Abstract: A method and system for scheduling events into a set of opportunities is presented. The method includes 1) dividing a path of an image acquisition device so that there is at least a first portion and a second portion at any given moment, wherein each of the first portion and the second portion includes at least one state and the first portion includes a null state in which no image is taken; 2) combining each state in the first portion with at least one state in the second portion one by one to generate a series of updated sequences; and 3) selecting at least one of the updated sequences based on a merit value associated with each of the updated sequences. The invention uses only two groups out of all the relevant opportunities for most calculations, and is especially applicable to situations like satellite pass scheduling.