Nucleic Acid Tagging and Amplification for Low-Input Form Analysis
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Solution Overview
Problem
Existing liquid biopsy assays for cancer detection face challenges due to low amounts of nucleic acids in body fluids and the heterogeneity of nucleic acid forms, leading to sensitivity issues and loss of data during analysis.
Innovation Solution
A method involving linking different forms of nucleic acids (e.g., double-stranded DNA, single-stranded DNA, single-stranded RNA) with specific tags, amplifying these tagged nucleic acids, and decoding the tags to reveal their forms, allowing for enhanced sensitivity and specificity in detecting somatic or germline variants, copy number variations, and other genetic markers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If nucleic acids are amplified to increase detection sensitivity, then sensitivity is improved, but loss of original material and data increases
Solution Approach 1:
The patent segments the nucleic acid population into different forms (single-stranded DNA, double-stranded DNA, single-stranded RNA) and applies form-specific tagging strategies. This segmentation allows selective amplification of relevant forms while preserving information about the original heterogeneous population structure, thereby reducing unnecessary amplification of all forms and minimizing material loss.
Solution Approach 2:
The patent introduces nucleic acid tags as intermediary molecules that link to specific forms of nucleic acids. These tags serve as mediators that enable differentiation and selective amplification without requiring complete conversion or loss of the original nucleic acid forms. The tags preserve information about the original forms while enabling targeted detection and amplification.
2Adaptability or versatility
If all nucleic acid forms are analyzed together, then comprehensive detection is achieved, but analysis complexity and data loss increase
Solution Approach 1:
The patent divides the complex heterogeneous nucleic acid population into distinct form-based groups, each tagged with specific nucleic acid tags. This segmentation simplifies the analysis process by enabling form-specific processing strategies while maintaining comprehensive detection capability through multiplexed tagging and decoding of all forms.
Solution Approach 2:
The patent applies different tagging strategies and processing conditions to different forms of nucleic acids based on their local characteristics. Single-stranded nucleic acids receive different treatment than double-stranded nucleic acids, optimizing detection for each form while reducing overall complexity by avoiding uniform processing of all forms.
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
The method significantly improves the sensitivity of detecting genetic variations by distinguishing and amplifying different nucleic acid forms, enabling accurate detection of cancer-related markers from low quantities of nucleic acids in bodily fluids.
Implementation Method 1
linking at least one of the forms of nucleic acid with at least one tag nucleic acid
Implementation Method 2
amplifying the forms of nucleic acid at least one of which is linked to at least one nucleic acid tag
Data Source
AI summary
The disclosure provides methods for processing nucleic acid populations containing different forms (e.g., RNA and DNA, single-stranded or double-stranded) and/or extents of modification (e.g., cytosine methylation, association with proteins). These methods accommodate multiple forms and/or modifications of nucleic acid in a sample, such that sequence information can be obtained for multiple forms. The methods also preserve the identity of multiple forms or modified states through processing and analysis, such that analysis of sequence can be combined with epigenetic analysis.