Machine Learning Biomarker Prediction in Digital Pathology

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Solution Overview

Problem

Current digital pathology methods require costly and time-consuming staining processes to identify biomarkers in tissue samples, limiting high-throughput screenings due to the expense and scarcity of tissue samples and staining materials.

Innovation Solution

A machine learning-based method that uses trained logic to identify biomarkers in tissue samples from images acquired through autofluorescence, X-ray, or non-biomarker specific stains, allowing for the prediction of biomarker presence without the need for additional staining, thereby reducing costs and time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If biomarker-specific staining is performed to identify biomarkers in tissue samples, then measurement precision is improved, but loss of time and loss of substance worsen due to the time-consuming and expensive staining process

Engineering Contradiction:
Improvebiomarker identification accuracyVSAvoidstaining process time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by performing biomarker-specific staining only on a subset of training images during the machine learning model training phase, rather than staining all images. The trained model then predicts biomarker presence in additional images without requiring actual staining, thus eliminating the time-consuming staining step for the majority of samples while maintaining identification accuracy.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses copying by creating virtual staining results through machine learning predictions. Instead of physically staining each tissue sample, the trained model generates predicted staining patterns that replicate the appearance and information of actual biomarker-specific stains, allowing multiple copies of staining information to be obtained from a single physical staining process.

Inventive Principle:
Principle #26Copying

2Measurement precision

If multiple biomarker-specific stains are applied to tissue samples, then measurement precision is improved, but loss of substance worsens due to the scarcity and expense of tissue samples and staining materials

Engineering Contradiction:
Improvebiomarker detection accuracyVSAvoidtissue sample and staining material consumption
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The patent applies universality by training a single machine learning model to predict multiple different biomarkers simultaneously. The model learns to identify patterns associated with various biomarkers from training images stained with different biomarker-specific stains, then applies this learned knowledge to predict the presence of any of these biomarkers in new images without requiring actual multiple staining processes, thus making one model serve multiple detection functions.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent uses copying by generating virtual staining results for multiple biomarkers through the trained model. Instead of consuming expensive tissue samples and staining materials for each biomarker detection, the model creates multiple copies of staining information predictions from a single input image, eliminating the need for multiple physical staining processes on the same scarce tissue sample.

Inventive Principle:
Principle #26Copying

3Reliability

If conventional image analysis methods are used to identify biomarkers, then reliability is maintained, but productivity worsens due to the inability to perform high-throughput screenings

Engineering Contradiction:
Improvediagnosis accuracyVSAvoidscreening throughput
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies mechanics substitution by replacing the mechanical staining process with a computational machine learning prediction system. The trained model processes images computationally to predict biomarker presence, substituting the physical chemistry-based staining mechanism with an information-processing approach that can handle large volumes of images rapidly while maintaining diagnostic reliability through the model's learned patterns.

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

Solution Approach 2:

The patent uses preliminary action by performing the computationally intensive model training phase in advance using a relatively small set of stained training images. Once trained, the model can rapidly process numerous additional images without requiring the time-consuming staining process, thus enabling high-throughput screening while maintaining the reliability established during the preliminary training phase.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS11482320B2Transformation of digital pathology images
Publication Date: 2022.10.25 F HOFFMANN LA ROCHE INC
  • US11482320B2 patent drawing
  • US11482320B2 patent drawing
  • US11482320B2 patent drawing

AI summary

The invention relates to a method of identifying a biomarker in a tissue sample. The method comprises receiving an acquired image depicting a tissue sample, the pixel intensity values of the acquired image correlating with an autofluorescence signal or of an X-ray induced signal or a signal of a non-biomarker specific stain or a signal of a first biomarker specific stain adapted to selectively stain a first biomarker. The acquired image is input into a trained machine learning logic—MLL which automatically transforms the acquired image into an output image highlighting tissue regions predicted to comprise a second biomarker.