Triplex Oligonucleotide Affinity Prediction With Pre-Trained Models

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Solution Overview

Problem

Traditional methods for measuring the binding affinity of triplex forming oligonucleotides (TFOs) to triplex target sites (TTSs) in double-stranded DNA are time-consuming and resource-intensive, requiring precise experimental efforts.

Innovation Solution

A method using a pre-trained machine learning model that processes sequence features of TFOs and TTSs to estimate binding affinity, incorporating nucleotide frequencies, structural features, and biophysical measurements to predict binding strength without physical measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional experimental methods are used to measure binding affinity, then measurement precision is improved, but time consumption and resource consumption increase

Engineering Contradiction:
Improvebinding affinity measurement precisionVSAvoidtime consumption
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent creates a computational model that copies and processes sequence information of TFOs and TTSs to predict binding affinity, replacing physical experimental measurements with in silico simulations. This allows rapid prediction without time-consuming laboratory work while maintaining predictive accuracy through trained machine learning algorithms.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent substitutes the mechanical experimental measurement system with a computational information processing system. Instead of physically measuring binding affinity through experiments, the system processes sequence features and structural parameters through machine learning models to generate predictions, eliminating the need for physical measurement apparatus and time-consuming experimental procedures.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If traditional experimental methods are used to measure binding affinity, then measurement precision is improved, but resource consumption increases

Engineering Contradiction:
Improvebinding affinity measurement precisionVSAvoidresource consumption
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent uses computational copying of sequence information and structural features to predict binding affinity, eliminating the need for physical consumption of reagents, materials, and experimental resources. The system processes digital representations of TFO and TTS sequences to generate predictions without requiring physical substances.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent replaces resource-intensive experimental measurement systems with a computational system that processes sequence data and structural parameters. This substitution eliminates consumption of physical resources such as reagents, equipment, and laboratory materials while maintaining the ability to assess binding affinity with high precision.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Loss of time

If computational model is used to estimate binding affinity, then time consumption is reduced, but measurement precision may deteriorate

Engineering Contradiction:
Improvetime consumptionVSAvoidbinding affinity estimation precision
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent performs preliminary training of the machine learning model using experimentally determined binding affinities for many TFO-TTS pairs. This preliminary action creates a trained computational model that can rapidly predict binding affinity for new sequences without requiring time-consuming experimental measurements, while maintaining precision through the learned patterns from training data.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent copies and processes sequence features, structural parameters, and biophysical measurements through the trained machine learning model to generate binding affinity predictions. This computational copying and processing enables rapid estimation while maintaining precision by incorporating multiple relevant features and their interactions into the prediction model.

Inventive Principle:
Principle #26Copying

Data Source

PatentEP4600962A1Method and system for estimating a binding affinity of a triplex forming oligonucleotide
Publication Date: 2025.08.13 UNIVERSITY OF REGENSBURG
  • EP4600962A1 patent drawingFigure 1A~1E
  • EP4600962A1 patent drawingFigure 2A~2D
  • EP4600962A1 patent drawingFigure 3A~3C

AI summary

The present invention provides a method for estimating a binding affinity of a triplex forming oligonucleotide, TFO, at a triplex target site, TTS, of a double-stranded DNA, dsDNA, the method comprising: - obtaining a plurality of TFO features based on sequence information of the TFO and a plurality of TTS features based on sequence information of the TTS, and - processing the plurality of TFO features and the plurality of TTS features in a pre-trained model to estimate the binding affinity.