Method of profiling diseases
AssigneeAkrivia Biomedics Limited
InventorAmit Gupta
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Abstract
The present invention provides a method of stratifying genomic aberrations associated with a disease and subjects suffering from a disease comprising at least one of the same genomic aberrations. Also provided are methods of determining the prognosis of the subject as well as methods of determining a treatment plan for the subject. In addition, the invention provides computer programs and apparatus, such as a computer, for executing the methods of the invention. Further provided are methods of identifying biomarkers for stratified subjects and databases and/or models for stratifying subject using the methods of the invention.
Claims51
-46. (canceled)
A method of classifying one or more genomic aberrations associated with a disease, the method comprising:
- a. identifying genes in a plurality of control subjects suffering from the disease that undergo a change of expression in response to a first genomic aberration from a plurality of genomic aberrations;
- b. selecting the genes that undergo a change of expression in response to the first genomic aberration to provide a first set of differentially expressed genes (DEGs) associated with the first genomic aberration;
- c. identifying DEGs of the first set of DEGs that overlap with DEGs of a control set of DEGs for a control genomic aberration and selecting the overlapping DEGs to form a first set of overlapping DEGs;
- d. comparing a fold direction of change of expression of each DEG of the first set of overlapping DEGs to a fold direction change of expression of the corresponding DEG of a control set of DEGs;
- e. classifying the first genomic aberration into a first or second group wherein:
- i. the first group comprises at least 51% overlapping DEGs that comprises the fold direction of change of expression that is the same as the fold direction of change of expression as the corresponding DEG of the control genomic aberration (Group A);
- ii. the second group comprises at least 51% overlapping DEGs that comprise a fold direction of change of expression that is inverse to the fold direction of change of expression of the corresponding DEG of the control genomic aberration (Group B).
A computer readable medium having computer executable instructions that when executed by a processor of a computing system causes the computing system to execute the steps of:
- a. generating a classification model for classifying genomic aberrations;
- b. stratify patients into one or more groups;
- c. identify genes in a plurality of control subjects suffering from the disease that undergo a change of expression in response to a first genomic aberration and selecting the genes that undergo a change of expression in response to the first genomic aberration to provide a first set of differentially expressed genes (DEGs) associated with the first genomic aberration;
- d. identify DEGs of the first set of DEGs that overlap with DEGs of a control set of DEGs for a control genomic aberration and selecting the overlapping DEGs to form a first set of overlapping DEGs;
- e. compare the fold direction of change of expression of each DEG of the first set of overlapping DEGs to a fold direction change of expression of the corresponding DEG of the control set of DEGs;
- f. classify the first genomic aberration into a first or second group wherein:
- i. the first group comprises at least 51% overlapping DEGs that comprises a fold direction of change of expression that is the same as the fold direction of change of expression as the corresponding DEG of the control genomic aberration (Group A);
- ii. the second group comprises at least 51% overlapping DEGs that comprise a fold direction of change of expression that is inverse to the fold direction of change of expression of the corresponding DEG of the control genomic aberration (Group B);
- g. generate a model comprising at least one classified genomic aberration;
- h. calculate a risk score for the subject based on the classified genomic aberration, wherein the calculated risk score is indicative of prognosis of the subject;
- and
- i. stratify the subject based on the risk score.
- j. determine one or more group-specific biomarkers for each of a Tier 1, a Tier 2, a Tier 3, a Tier 4, a Tier 5 and/or Tier 6 groups, wherein the group-specific biomarkers are determined by one or more omics-based methods, such as proteomic analysis, transcriptomic analysis, Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), over-representation analysis, pathway/network enrichment analysis, single sample Gene Set Enrichment Analysis (ssGSEA), epigenetic analysis, and/or metabolomic analysis;
- and
- k. predict a prognosis of a subject suffering from a disease comprising:
- i. determining one or more group-specific biomarkers;
- ii. measuring a level of one or more of the group-specific biomarkers in a sample obtained from the subject;
- iii. classifying the subject into one or more of the Tier 1, Tier 2, Tier 3, Tier 4, Tier 5 and/or Tier 6 groups based on the level of the one or more of group-specific biomarkers;
- and
- iv. predicting the prognosis of the subject based on the classification.
Dependencies are inferred from the claim text.