Microbial Cell-Free Nucleic Acid Enrichment Through Mammalian Depletion
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Solution Overview
Problem
The detection of circulating microbial cell-free nucleic acid molecules for disease diagnosis and prognosis is challenging due to their presence in small quantities and being overshadowed by mammalian cell-free nucleic acids.
Innovation Solution
A method involving the depletion of mammalian cell-free nucleic acids using affinity agents, such as anti-nucleosome antibodies, followed by sequencing and enrichment of microbial nucleic acids to generate a microbial metagenomic feature set for disease differentiation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If direct sequencing of total cell-free nucleic acids is performed, then all nucleic acid molecules are captured, but microbial nucleic acids are overwhelmed by mammalian nucleic acid background
Solution Approach 1:
The patent extracts and removes mammalian nucleic acid molecules from the complex mixture of cell-free nucleic acids using affinity capture reagents. This extraction principle isolates the target microbial nucleic acids from the overwhelming mammalian background, enabling their detection despite their low relative abundance in the original sample.
Solution Approach 2:
The patent introduces affinity capture reagents as intermediary substances that selectively bind to mammalian nucleic acids. These reagents act as mediators to facilitate the separation of mammalian and microbial nucleic acids, allowing the microbial targets to be enriched without direct manipulation of the microbial molecules themselves.
2Measurement precision
If affinity capture reagents are used to remove mammalian nucleic acids, then microbial nucleic acid enrichment is achieved, but additional processing steps are required
Solution Approach 1:
The patent combines multiple functions into the affinity capture reagents, which simultaneously serve as selective binding agents for mammalian nucleic acids and as capture vehicles for enrichment. By integrating the removal and enrichment functions into a single reagent system, the patent reduces the need for separate processing steps while achieving both mammalian nucleic acid removal and microbial nucleic acid enrichment.
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 detection and enrichment of microbial nucleic acids, allowing for accurate differentiation between cancer and non-oncologic diseases through the generation of microbial metagenomic features.
Implementation Method 1
affinity agents, configured to selectively bind to one or more mammalian cell-free nucleic acid molecules
Data Source
AI summary
Provided are systems and methods for enriching cell-free microbial nucleic acids from one or more subjects' samples.