Hybridization Capture Probes for Nucleic Acid Selection
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Solution Overview
Problem
Current nucleic acid selection methods for complex genomic mixtures, such as PCR and rolling circle amplification, often result in sequence distortion and bias, making it difficult to accurately select relevant sequences for medical applications.
Innovation Solution
A method involving hybridization of nucleic acids with capture probes attached to a solid support, allowing for the selection of a representational sample with a complexity of less than 10% but more than 0.001% of the original mixture, ensuring proportional representation of sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If PCR or rolling circle amplification is used to select nucleic acid sequences, then sequence selection capability is improved, but sequence distortion and bias increase
Solution Approach 1:
The patent extracts and removes amplification steps from the nucleic acid selection process. Instead of using PCR or rolling circle amplification to enrich target sequences, the invention directly selects and isolates nucleic acid sequences from complex mixtures using hybridization-based capture methods, thereby eliminating the source of amplification bias and distortion while maintaining sequence selection capability
Solution Approach 2:
The patent introduces capture probes as intermediary molecules that mediate the selection process. These probes hybridize to target nucleic acid sequences in the complex mixture, allowing for specific capture and isolation without requiring amplification. The probes act as intermediaries that enable direct selection while preserving the original sequence representation and avoiding amplification-induced distortion
2Speed
If conventional nucleic acid selection methods are used, then processing speed is improved, but sequence variance and bias increase
Solution Approach 1:
The patent replaces mechanical amplification processes (PCR, rolling circle) with a hybridization-based selection system. This substitution eliminates the mechanical biases inherent in amplification while maintaining efficient processing speeds through parallel hybridization reactions and selective capture, achieving both speed and accuracy
3Productivity
If high throughput nucleic acid analysis is performed on complex mixtures, then productivity is improved, but sequence distortion increases
Solution Approach 1:
The patent segments the complex nucleic acid mixture into discrete selectable units through hybridization with specific capture probes. Each probe-target complex can be independently captured and isolated, enabling high throughput processing while maintaining precise sequence representation. This segmentation allows parallel processing of multiple sequences without the distortion effects of bulk amplification
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 provides an accurate and unbiased selection of nucleic acid sequences, reducing sequence variance and enabling more precise downstream analysis, including diagnostic and therapeutic applications.
Implementation Method 1
contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids to form hybridization complexes
Data Source
AI summary
The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture.