Phenotypic Screening System for Polypharmacological Drug Discovery

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Conventional high throughput screening (HTS) methodologies are inefficient as they require a substantial understanding of the disease etiology to design target-specific assays, making it difficult to identify candidate drugs acting through unknown molecular targets or with complex polypharmacological effects. Additionally, these methods struggle to differentiate between on-target and off-target effects, necessitating separate screens and increasing the cost and time of drug discovery.

Innovation Solution

The development of systems and methods for screening compound libraries in a target-agnostic fashion, utilizing automated biology and machine learning to measure high-dimensional phenotypes across multiple disease models. This approach allows for the identification of compounds that rescue cellular disease phenotypes with minimal off-target effects, facilitating the evaluation of on-target and off-target effects in a single assay.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If target-specific assays are used in conventional HTS, then the screening can identify compounds with known mechanisms of action, but it requires substantial understanding of disease etiology and cannot capture polypharmacological effects or unknown targets

Engineering Contradiction:

Improveability to identify compounds with known mechanismsVSAvoidability to screen for unknown targets and polypharmacological effects

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent implements a universal phenotypic screening platform that can evaluate compounds across multiple disease models and biological contexts simultaneously. Instead of developing separate target-specific assays for different diseases, the system uses high-dimensional phenotype measurements that capture cellular responses across diverse conditions, enabling one assay to serve multiple screening purposes and identify both known and unknown mechanisms of action.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent transitions from low-dimensional target-specific measurements to high-dimensional phenotypic measurements that capture multiple cellular parameters simultaneously. By measuring numerous phenotypic features across different disease models, the system creates a multidimensional characterization of compound effects, enabling detection of polypharmacological effects and unknown mechanisms that would be invisible in traditional single-parameter assays.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Measurement precision

If separate screens are conducted for on-target and off-target effects, then each effect can be evaluated in detail, but the cost and time of drug discovery increases significantly

Engineering Contradiction:

Improveability to evaluate on-target and off-target effects separatelyVSAvoidtime required for multiple separate screens

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent merges the evaluation of on-target and off-target effects into a single integrated phenotypic screening assay. By simultaneously measuring multiple phenotypic parameters across different disease models in one experiment, the system captures both desired on-target effects and unwanted off-target effects without requiring separate screening campaigns, thereby reducing time and resource requirements while maintaining comprehensive evaluation capability.

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If conventional HTS methods are used, then the screening process is well-established, but it is inefficient for diseases with poorly understood etiologies and requires substantial capital, labor, and time investment

Engineering Contradiction:

Improveestablished screening methodologyVSAvoidspeed and cost efficiency of drug discovery

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent replaces the mechanical, step-by-step conventional HTS approach with an automated, high-throughput phenotypic screening system that leverages automated biology and machine learning. This substitution enables rapid evaluation of compounds across multiple disease models simultaneously, dramatically increasing productivity and reducing the capital, labor, and time investment required compared to traditional sequential screening methods.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20250078976A1Systems and methods for evaluating query perturbations

Publication Date: 2025.03.06 RECURSION PHARMACEUTICALS INC

AI summary

Methods and systems for evaluating a query perturbation, in a cell based assay representing a test state, are provided. Control data points having dimensions representing measurements of different features across control cell aliquots are obtained. Test data points having dimensions representing measurements of different features across test cell aliquots are obtained. A composite test vector is computed between measures of central tendency across the control data points and measures of central tendency across the test data points. Query perturbation data points having dimensions representing measurements of different features across perturbation cell aliquots are obtained. A composite query perturbation vector is computed between measures of central tendency across the control data points and measures of central tendency across the plurality of query perturbation data points.