Notch Pathway Activity Inference via Target Gene Expression Modeling
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Solution Overview
Problem
Current clinical assays lack the ability to assess the functional state of the Notch cellular signaling pathway, which is crucial for detecting abnormal activity associated with cancer and immune disorders, hindering the selection of appropriate targeted drug treatments.
Innovation Solution
A computer-implemented method inferring Notch cellular signaling pathway activity in a subject by measuring and analyzing the expression levels of specific target genes using a calibrated mathematical model, such as a Bayesian network, to determine the activity level of the Notch transcription factor element, allowing for improved characterization and treatment determination of diseases like breast, cervical, endometrial, ovarian, and prostate cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If clinical assays are developed to assess Notch pathway activity, then diagnostic accuracy and treatment selection improve, but device complexity and measurement difficulty increase
Solution Approach 1:
The patent uses target gene expression levels as intermediary markers to indirectly measure Notch pathway activity. Instead of directly measuring the complex signaling pathway, the assay measures the expression of downstream target genes (HES1, HES5, HEY1, HEY2, MAML1) which are regulated by the Notch pathway, thereby simplifying the measurement while maintaining diagnostic accuracy
Solution Approach 2:
The patent replaces complex functional assays with mathematical modeling and computational analysis. By using calibrated mathematical models to infer pathway activity from gene expression data, the system substitutes direct biochemical measurement with computational prediction, reducing experimental complexity while improving measurement precision
2Reliability
If multiple target genes are measured to improve assessment reliability, then diagnostic reliability improves, but device complexity and analysis burden increase
Solution Approach 1:
The patent divides the Notch pathway assessment into multiple independent gene expression measurements (HES1, HES5, HEY1, HEY2, MAML1). Each gene serves as an independent indicator that can be measured separately using standard qPCR or RNA-seq techniques, allowing the complex pathway assessment to be segmented into manageable, routine molecular biology procedures
Solution Approach 2:
The patent employs a panel of target genes that can be measured using universal, widely-available molecular techniques such as quantitative PCR and RNA sequencing. This multi-gene approach uses standard laboratory methods that are already established in clinical laboratories, thereby increasing reliability without proportionally increasing device complexity
Data Source
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AI summary
The present invention relates to a computer-implemented method for inferring activity of a Notch cellular signaling pathway in a subject based on expression levels of three or more target genes of the Notch cellular signaling pathway measured in a sample of the subject. The present invention further relates to an apparatus, to a non-transitory storage medium, and to a computer program for inferring activity of a Notch cellular signaling pathway in a subject. The present invention further relates to a kit for measuring expression levels of three or more target genes of the Notch cellular signaling pathway in a sample of a subject, to a kit for inferring activity of a Notch cellular signaling pathway in a subject, and to the use of such kits in performing the method.