T Cell Balance Gene Expression Regulatory Network

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Solution Overview

Problem

The molecular circuits controlling T cell balance, including Th17 cell differentiation, maintenance, and function, remain poorly understood, limiting the development of effective therapeutic and diagnostic methods.

Innovation Solution

Development of T cell modulating agents that target specific genes and gene products associated with Th17 cell regulation, allowing for modulation of T cell balance through up-regulation, down-regulation, or inhibition of gene expression and activity to influence T cell differentiation, maintenance, and function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If perturbation-based approaches are used to reconstruct regulatory networks, then short-term responses can be studied, but the approach cannot be readily applied to primary T cells

Engineering Contradiction:
Improveregulatory network reconstructionVSAvoidapplicability to primary T cells
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent uses computational algorithms as intermediaries to analyze gene expression data from primary T cells without requiring direct perturbation of the cells. The CEMRA and ICMRA algorithms process transcriptomic data to reconstruct regulatory networks, allowing indirect study of T cell regulation while maintaining cell integrity and physiological relevance.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of time

If existing regulatory network methods are applied, then short-term responses can be analyzed, but dynamic long-term T cell balance modulation cannot be understood

Engineering Contradiction:
Improveresponse time scaleVSAvoiddynamic regulatory network information
Core Design Contradiction:
Loss of timeVSLoss of information

Solution Approach 1:

The patent employs dynamic regulatory network analysis methods that track gene expression changes over extended periods. The computational algorithms model temporal relationships between transcription factors and target genes, enabling reconstruction of both short-term and long-term regulatory dynamics in T cell differentiation and balance.

Inventive Principle:
Principle #15Dynamics

3Productivity

If molecular circuits controlling T cell balance are not understood, then therapeutic development is limited, but researching these circuits increases complexity

Engineering Contradiction:
Improvetherapeutic development efficiencyVSAvoidresearch methodology complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent segments the complex regulatory network into manageable components by identifying key transcription factors, target genes, and regulatory modules. This modular approach breaks down the intricate molecular circuits into discrete functional units that can be individually analyzed and targeted for therapeutic development.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP3514246B1T cell balance gene expression and methods of use thereof
Publication Date: 2021.11.17 THE BROAD INST INC
  • EP3514246B1 patent drawingFigure 1A
  • EP3514246B1 patent drawingFigure 1B
  • EP3514246B1 patent drawingFigure 1C

AI summary

This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences T cell balance, for example, Th17 cell differentiation, maintenance and/or function, as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences T cell balance in a variety of therapeutic and/or diagnostic indications. This invention also relates generally to identifying and exploiting target genes and/or target gene products that modulate, control or otherwise influence T cell balance in a variety of therapeutic and/or diagnostic indications.