Tagged Nucleic Acid Analysis for Sensitive Liquid Biopsy Sequencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing liquid biopsy assays for cancer detection face challenges in sensitivity due to low amounts and heterogeneity of nucleic acids in body fluids, such as RNA and DNA, which are often lost during processing.
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 and assaying sequence data to distinguish and decode the forms, and enriching for specific forms to enhance sensitivity and reduce loss.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid biopsy assays are used to detect cancer from cell-free nucleic acids in body fluids, then noninvasive detection is achieved, but sensitivity is reduced due to low amounts and heterogeneity of nucleic acids
Solution Approach 1:
The patent segments the heterogeneous nucleic acid population into distinct groups based on form (double-stranded DNA, single-stranded DNA, single-stranded RNA) by linking each form with specific tags. This segmentation allows for targeted amplification and analysis of each nucleic acid form, improving sensitivity while maintaining the noninvasive liquid biopsy approach.
Solution Approach 2:
The patent introduces tag nucleic acids as intermediaries that link to different forms of cell-free nucleic acids. These tags serve as mediators that enable selective amplification and identification of specific nucleic acid forms, thereby enhancing detection sensitivity without compromising the noninvasive nature of the assay.
2Measurement precision
If amplification is performed on heterogeneous nucleic acid forms, then sensitivity is improved, but loss of original nucleic acid material increases
Solution Approach 1:
By segmenting the nucleic acid population into distinct tagged groups, the patent enables selective amplification of only those forms that are present and detectable. This reduces unnecessary amplification cycles and minimizes loss of original nucleic acid material while still achieving the sensitivity needed for detection.
Solution Approach 2:
The patent changes the physical-chemical parameters of the nucleic acids by introducing tags that enable form-specific amplification. This allows for optimized amplification conditions for each nucleic acid form, improving sensitivity while reducing overall material loss through more efficient amplification strategies.
3Adaptability or versatility
If different forms of nucleic acids are analyzed together, then comprehensive cancer detection is achieved, but complexity of the assay increases
Solution Approach 1:
The patent segments the analysis into distinct tagged groups for different nucleic acid forms, allowing for systematic and organized processing. This segmentation reduces assay complexity by providing clear protocols for each form while maintaining comprehensive detection capabilities across all nucleic acid types.
Solution Approach 2:
The patent employs universal tagging strategies and amplification protocols that can be applied across different nucleic acid forms. This multi-functional approach allows comprehensive detection of DNA and RNA while using a unified assay framework, thereby reducing overall complexity despite the versatility of detection.
4Measurement precision
If tagging is used to distinguish nucleic acid forms, then sensitivity and specificity are improved, but device complexity increases
Solution Approach 1:
The patent uses tag nucleic acids as intermediaries that provide form-specific identification. These tags enable sensitive and specific detection of different nucleic acid forms while using a relatively simple tagging mechanism that does not overly complicate the overall assay design or required equipment.
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
Enhances the sensitivity of nucleic acid analysis in liquid biopsies by effectively distinguishing and amplifying different forms of nucleic acids, allowing for better detection of somatic variants, copy number variations, and other genetic markers.
Implementation Method 1
linking at least one of the forms of nucleic acid with at least one tag nucleic acid to distinguish the forms from one another
Implementation Method 2
amplifying the forms of nucleic acid at least one of which is linked to at least one nucleic acid tag, wherein the nucleic acids and linked nucleic acid tag, if present, are amplified
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.