Chromosome Interaction Biomarker Detection for Therapy Response

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Solution Overview

Problem

Current methods fail to accurately predict patient responses to therapies due to the complexity of disease processes and the variability in molecular biomarkers, making it challenging to stratify patient cohorts effectively.

Innovation Solution

The development of a process to determine immunoresponsiveness by identifying specific chromosome interactions using the EpiSwitch system, which generates ligated nucleic acids from cross-linked chromosomal regions, allowing for the detection of binary 'yes or no' biomarkers that reflect a patient's responsiveness to therapies like anti-PD-1 or anti-PD-L1 treatments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If continuum read-out methods (DNA methylation, histone modifications, non-coding RNAs) are used to measure molecular biomarkers, then comprehensive molecular information is obtained, but data analysis becomes challenging due to varying magnitudes of change between patients

Engineering Contradiction:
Improvemolecular informationVSAvoiddata classification accuracy
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The invention transforms the measurement parameter from continuous (magnitude of biomarker expression) to discrete (binary presence/absence of chromosome conformation). This parameter change resolves the data analysis challenge by converting variable-magnitude continuous data into standardized binary states that are easier to classify and compare across patients.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a simplified binary copy of the complex continuous biomarker data. Instead of analyzing the full continuum of biomarker expression levels, the method captures the essential diagnostic information in a binary format (chromosome interaction present/absent), which preserves the phenotypic distinction while eliminating the complexity of varying magnitudes.

Inventive Principle:
Principle #26Copying

2Measurement precision

If chromosome conformation interactions are used as binary biomarkers, then data classification is simplified, but the method complexity increases due to chromosome conformation detection

Engineering Contradiction:
Improvebinary classification accuracyVSAvoidchromosome detection system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts the essential diagnostic information from complex chromosome conformation data by focusing on specific binary outcomes (presence/absence of interaction). This extraction approach simplifies the overall system by isolating the critical diagnostic feature while eliminating the need to process and interpret the full complexity of chromosome conformation dynamics.

Inventive Principle:
Principle #2Taking out (Extraction)

3Loss of information

If traditional biomarker methods are used to predict therapy response, then existing molecular data is utilized, but prediction accuracy fails due to disease complexity and patient variability

Engineering Contradiction:
Improveprediction accuracyVSAvoidpatient stratification capability
Core Design Contradiction:
Loss of informationVSAdaptability or versatility

Solution Approach 1:

The invention changes the fundamental parameter being measured from molecular expression levels to three-dimensional chromosome conformation states. This parameter change enables more accurate prediction of therapy response by capturing the functional organizational state of the genome, which directly regulates gene expression programs relevant to disease and therapy response.

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach provides a personalized and accurate assessment of a patient's responsiveness to cancer therapies, enabling tailored treatment strategies by identifying stable chromosome interactions that are less variable between individuals within the same subgroup, thus improving treatment efficacy.

Implementation Method 1

generates ligated nucleic acids from cross-linked chromosomal regions

Methodology Applied
Scientific EffectCross-linking:

Data Source

PatentEP3704274B1Genetic regulation of immunoresponse by chromosome interactions
Publication Date: 2024.04.17 OXFORD BIODYNAMICS PLC
  • EP3704274B1 patent drawingFigure 1
  • EP3704274B1 patent drawingFigure 2
  • EP3704274B1 patent drawingFigure 3

AI summary

A process for analysing chromosome regions and interactions relating to immunoresponsiveness.