Dynamic Pathway Map Generation via Probabilistic Model Integration
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Solution Overview
Problem
Current pathway analysis methods are limited in incorporating multiple types of genome-wide data and fail to account for interdependencies among genes, leading to restricted analytic and predictive value, especially in global analyses, and do not adequately represent the diverse roles of pleiotropic functional nucleic acids.
Innovation Solution
The development of systems and methods that integrate multiple attributes of pathway elements to construct a probabilistic pathway model, allowing for the generation of dynamic pathway maps by cross-correlating and assigning influence levels to elements, using a priori known and assumed attributes, and modifying these models with measured attributes from patient samples to provide reference pathway activity information.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If a single type of genome-wide data is used in pathway analysis, then the analysis method remains simple and computationally manageable, but the analytic and predictive value is highly restricted
Solution Approach 1:
The patent combines multiple types of genome-wide data (gene expression, DNA methylation, somatic mutations, gene copy number, microRNA expression) into a unified pathway analysis framework. This integration allows the system to leverage complementary information from different data types, thereby enhancing predictive accuracy and analytical value while maintaining a coherent analysis structure.
Solution Approach 2:
The patent creates a composite analytical model that integrates multiple data types with different characteristics and information content. Each data type contributes unique biological insights, and their combination produces a more robust and comprehensive pathway analysis that overcomes the limitations of any single data type alone.
2Device complexity
If pathway elements are treated independently without considering interdependencies, then the analysis computation is simpler, but the detection signal for pathway relevance is reduced
Solution Approach 1:
The patent implements feedback mechanisms where pathway element states are updated based on their interactions with other elements. The system iteratively refines pathway activity scores by considering how changes in one element affect others, allowing the detection of emergent pathway-level signals that arise from element interdependencies rather than isolated changes.
Solution Approach 2:
The patent creates a unified pathway analysis model that simultaneously evaluates multiple data types and captures multiple levels of biological organization (individual genes, pathways, and network interactions). This multi-functional approach allows the same framework to detect both individual element alterations and coordinated pathway-level changes.
3Ease of manufacture
If all gene alterations are treated as equal, then the analysis method is simpler to implement, but the biological representation is not representative of most biological systems
Solution Approach 1:
The patent assigns different weights and characteristics to different types of gene alterations based on their biological significance. For example, somatic mutations, gene amplifications, and DNA methylation events are treated with different priorities and influence levels, reflecting their distinct roles in disease pathogenesis and allowing the model to capture nuanced biological realities.
Solution Approach 2:
The patent introduces multiple parameters to characterize gene alterations, including alteration type, magnitude, and biological context. These parameters allow the model to differentiate between various kinds of genetic changes and their differential impacts on pathway activity, providing a more realistic representation of biological systems.
4Device complexity
If pleiotropic functional nucleic acids are not considered to act in multiple pathways, then the analysis model is simpler, but the diverse roles of these molecules are not adequately represented
Solution Approach 1:
The patent explicitly models pleiotropic functional nucleic acids (such as microRNAs) as capable of acting in multiple pathways with different roles. The framework allows a single nucleic acid molecule to have multiple target genes across different pathways, capturing its diverse biological functions and enabling the analysis to reflect the true complexity of molecular networks.
Data Source
AI summary
A method of generating a dynamic pathway map (DPM) is provided. The method includes accessing a model database that stores a probabilistic pathway model that comprises a plurality of pathway elements, a first number of the plurality of pathway elements are cross-correlated and assigned an influence level for at least one pathway on the basis of known attributes, a second number of the plurality of pathway elements are cross-correlated and assigned an influence level for at least one pathway on the basis of assumed attributes. The method includes measuring a patient sample to identify measured attributes of the patient sample and using a plurality of the measured attributes of the patient sample, via an analysis engine, to modify the probabilistic pathway model to obtain the DPM, wherein the DPM has reference pathway activity information for a particular pathway, the reference pathway indicating deviations from the probabilistic pathway model.