MODELING miRNA INDUCED SILENCING IN BREAST CANCER WITH PARADIGM
AssigneeMantomics, LLC
InventorsAndrew SEDGEWICK, Shahrooz RABIZADEH, Patrick SOON-SHIONG, Charles Joseph VASKE
Life of this patent
Estimating the term…
Abstract
A probabilistic graphical pathway model is modified to include miRNA regulation by adding RISC as a regulatory factor. Most preferably, the pathway model is built using factor graphs, and the RISC includes DICER, TARBP2, and AGO2 or AGO1/3/4. So constructed pathway models can be used to infer RISC activity, which can be associated with various clinically relevant parameters to build various predictors or diagnostic tests.
Claims25
A method of quantifying RNA-induced silencing complex (RISC) activity in a tumor tissue of a patient, comprising:
- obtaining omics data from a tumor tissue of the patient, wherein the tumor tissue is subtype luminal A breast cancer tissue;
- quantifying the RISC activity from the omics data using a probabilistic graphical pathway model having a plurality of pathway elements;
- wherein each of the pathway elements in the probabilistic graphical pathway model is represented by respective factor graphs;
- and
- wherein at least one of the factor graphs models the RISC and comprises at least one of AGO1, AGO2, AGO3, and AGO4.
A method of detecting RNA-induced silencing complex (RISC) activity in a tumor tissue of a patient, comprising:
- obtaining omics data from the tumor tissue of the patient;
- and
- detecting the RISC activity in the patient by inputting the omics into a probabilistic graphical pathway model, wherein the probabilistic graphical pathway model uses a priori known miRNA and respective miRNA targets;
- and
- calculating from the omics data in the pathway model a RISC activity.
A method of predicting overall survival of a patient having subtype luminal A breast cancer, comprising:
- obtaining omics data from a tumor tissue of the patient;
- quantifying the RISC activity from the omics data using a probabilistic graphical pathway model having a plurality of pathway elements;
- wherein each of the pathway elements in the probabilistic graphical pathway model is represented by respective factor graphs, and wherein at least one of the factor graphs models the RISC with AGO2;
- and
- diagnosing the patient as having a decreased overall survival when decreased RISC-AGO2 activity is detected.
A computer system for omics analysis, comprising:
- an omics database informationally coupled to an analysis engine;
- wherein the omics database stores omics data of a patient;
- wherein the analysis engine is programmed to:
- (a) receive the omics data from the omics database;
- (b) calculate, using the omics data and a probabilistic graphical pathway model a RISC activity;
- (c) wherein the probabilistic graphical pathway model has a plurality of pathway elements, and wherein each of the pathway elements in the probabilistic graphical pathway model is represented by respective factor graphs;
- and
- (d) wherein at least one of the factor graphs models the RISC and comprises at least one of AGO1, AGO2, AGO3, and AGO4.
Dependencies are inferred from the claim text.