Target Enrichment via Preliminary Fragmentation and Probe Hybridization

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Solution Overview

Problem

Current methods for analyzing genes require the creation of a DNA library, which is time-consuming, results in sample loss, and generates fragments with undefined locations, making it inefficient for enriching target sequences.

Innovation Solution

The method involves randomly fragmenting nucleic acids, adding target probes and enzymes to isolate specific sequences, and creating a target-enriched library by removing non-target nucleic acids, allowing for unbiased coverage of target regions for further studies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a DNA library is created prior to enrichment with target probes, then target sequences can be enriched, but the process is time-consuming and results in sample loss

Engineering Contradiction:
Improvetarget sequence enrichmentVSAvoidlibrary creation time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The method performs preliminary fragmentation of the nucleic acid sample before library creation and enrichment steps. By fragmenting the sample first and then using target probes to capture and enrich specific sequences directly from the fragmented pool, the workflow eliminates the time-consuming step of creating a complete library before enrichment, while still achieving reliable target sequence enrichment

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention extracts only the necessary components for target enrichment by using target probes to selectively capture and isolate specific nucleic acid sequences from the fragmented sample pool. This extraction approach avoids the need to process and store complete libraries, reducing time and sample loss while maintaining enrichment effectiveness

Inventive Principle:
Principle #2Taking out (Extraction)

2Reliability

If a DNA library is created prior to enrichment, then target sequences can be captured, but sample loss occurs and amplification is required

Engineering Contradiction:
Improvetarget sequence captureVSAvoidnucleic acid sample
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The method extracts and isolates only the target sequences of interest from the fragmented nucleic acid sample using complementary target probes. By directly capturing specific sequences from the fragmented pool without creating a complete library first, the process minimizes sample loss and eliminates the need for extensive amplification steps

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Target probes serve as intermediaries that mediate the selective capture and enrichment of specific nucleic acid sequences from the fragmented sample. These probes hybridize to complementary target sequences, enabling specific isolation and concentration of target regions without requiring library construction and reducing overall sample consumption

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If a DNA library is created with target probes, then enrichment can occur, but target regions are at undefined locations within fragments

Engineering Contradiction:
Improvetarget sequence enrichmentVSAvoidtarget location definition
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The method performs preliminary fragmentation of the nucleic acid sample into smaller pieces before applying target probes for enrichment. This preliminary fragmentation, combined with subsequent target-specific capture, ensures that target sequences are present in defined, recoverable fragments rather than at undefined locations within large library constructs, facilitating precise isolation and downstream analysis

Inventive Principle:
Principle #10Preliminary action

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 efficiently enriches target DNA/RNA sequences, reducing sample loss and time, while ensuring target sequences are isolated and amplified accurately, suitable for gene expression studies and disease-specific transcript identification.

Implementation Method 1

The nucleic acid sample is randomly fragmented into a pool of DNA fragments using physical or enzymatic methods

Methodology Applied
Scientific EffectPhysical fragmentation:

Implementation Method 2

The nucleic acid sample is randomly fragmented into a pool of DNA fragments using physical or enzymatic methods

Methodology Applied
Scientific EffectEnzymatic fragmentation: Enzyme

Implementation Method 3

The fragmented nucleic acid pool is hybridized with target probes or baits to capture and enrich the target sequences

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS9315807B1Genome selection and conversion method
Publication Date: 2016.04.19 NEW ENGLAND BIOLABS INC

AI summary

The present disclosure provides a method and a kit for selecting and enriching target sequences specific for one or more genomic regions of interest or a subset of a transcriptome using a target-capturing library of probes. The target-enriched library is generated from a random pool of deoxyribonucleic acid (DNA) fragments. The present disclosure provides an efficient and cost-effective method of target selection for targeted genome sequencing, targeted nucleic acid library creation and gene expression studies.