Probe Set Optimization for Rapid Pathogen Detection

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Solution Overview

Problem

Current diagnostic methods for infectious diseases in tropical developing countries are inefficient due to the need for extensive probe sets in hybrid selection, leading to resource-intensive and time-consuming processes, and often result in misdiagnoses, as they struggle to detect a broad spectrum of pathogens and emerging threats effectively.

Innovation Solution

A method involving the construction of candidate probes with hybridization patterns along a reference sequence, followed by a set cover solving process to reduce the number of probes, and subsequent synthesis of selected probes for hybridization and sequencing, enabling more rapid and cost-efficient pathogen detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a high number of candidate probes are used for hybrid selection to ensure comprehensive pathogen detection, then the detection coverage is improved, but the resource consumption and time required for analysis increase significantly

Engineering Contradiction:
Improvedetection coverageVSAvoidanalysis speed
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent extracts and removes redundant probes from the candidate probe set through iterative comparison. Probes that are shifted by less than a threshold distance and have mismatches within a threshold are identified as redundant and removed, keeping only the essential probes needed for comprehensive detection.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent designs candidate probes to collectively cover the entire target sequence space, where each probe serves multiple potential target regions. The probe set is constructed to be universally applicable across different pathogen variants while minimizing the total number of probes needed.

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

2Quantity of substance

If candidate probes are compared iteratively to reduce redundancy, then the number of probes is reduced, but the computational complexity and time for probe selection increase

Engineering Contradiction:
Improvenumber of probesVSAvoidprobe selection time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent performs preliminary ordering of candidate probes before the iterative comparison process. By establishing an initial order, the algorithm can efficiently proceed through the probe list in a single pass, comparing each probe only against previously selected probes rather than all possible combinations.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent segments the probe selection process into discrete iterative steps, where in each iteration one probe is selected and redundant probes are removed. This breaks down the complex optimization problem into manageable sequential operations that can be executed efficiently.

Inventive Principle:
Principle #1Segmentation

3Ease of manufacture

If the probe selection depends on candidate probe ordering, then the selection process is simpler, but the output quality and optimality of the selected probe set deteriorates

Engineering Contradiction:
Improveselection process simplicityVSAvoidprobe set optimality
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent implements a dynamic probe selection process where the candidate probe list is reordered in each iteration based on the currently selected probes. This allows the algorithm to adapt to the evolving probe set and make optimally informed selections at each step, improving overall probe set quality while maintaining computational efficiency.

Inventive Principle:
Principle #15Dynamics

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 allows for comprehensive and rapid pathogen detection, reducing the number of probes needed, improving diagnostic accuracy, and enabling early detection of emerging diseases, thereby enhancing healthcare delivery and patient outcomes in resource-limited settings.

Implementation Method 1

contacting the selected probes to the target sequence or a fragment thereof; wherein the target sequence or fragment thereof that hybridizes to one or more of the selected probes is sequenced

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS11332783B2Sample analysis, presence determination of a target sequence
Publication Date: 2022.05.17 THE BROAD INST INC
  • US11332783B2 patent drawing
  • US11332783B2 patent drawing
  • US11332783B2 patent drawing

AI summary

The present invention provides a combination of genomic and computational technologies to provide rapid, portable sample analysis for sequencing or identifying a target sequence involving generating probes for use in analyzing a sample which may comprise a target sequence.