Mutation Mapping of Distal Nucleic Acids for Source Localization
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Solution Overview
Problem
Existing diagnostic methods struggle to accurately determine the source of nucleic acids detected distal from their origin in the body, leading to limited sensitivity and difficulty in detecting and monitoring diseases, especially when nucleic acids from multiple sources combine, obscuring signals from specific body locations.
Innovation Solution
The method involves separating blood samples into cell-free and surface-bound nucleic acid components, sequencing them independently, and using a programmed computer processor to compare and identify differential mutations, generating a mutation map that relates mutations to their sources, enabling spatial localization and improved sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If nucleic acids are sampled distal from their source in the body, then easier access for detection is achieved, but the ability to determine the source tissue is lost
Solution Approach 1:
The patent creates a mutation map beforehand by sequencing nucleic acids from multiple tissue types and recording their unique mutation profiles. When distal nucleic acids are later detected, the pre-existing mutation map enables source identification without requiring direct tissue access, thus resolving the contradiction between easy sampling and source determination.
2Ease of operation
If nucleic acids from multiple sources are combined in bodily fluids, then easier non-invasive detection is enabled, but sensitivity to detect signals from any single source is limited
Solution Approach 1:
The patent segments the combined nucleic acid signal by identifying unique mutation profiles that distinguish nucleic acids from different tissue sources. This segmentation allows the detection system to resolve individual source signals within the combined mixture, thereby maintaining detection sensitivity despite the presence of multiple sources in non-invasive samples.
Solution Approach 2:
The patent uses mutation profiles as unique identifiers (analogous to color changes) to distinguish nucleic acid signals from different sources. By detecting specific mutation patterns, the system can identify and quantify signals from individual tissue types even when they are mixed together in bodily fluids, thus preserving sensitivity in non-invasive detection.
3Adaptability or versatility
If nucleic acid signals from multiple body parts are combined, then comprehensive health monitoring is achieved, but the ability to localize disease sources is lost
Solution Approach 1:
The patent performs preliminary sequencing of nucleic acids from multiple known tissue sources to create a reference mutation map. This pre-established spatial reference allows the system to maintain comprehensive monitoring capabilities while simultaneously preserving the ability to localize disease sources by matching detected mutations to their geographic origins in the mutation map.
Solution Approach 2:
The patent applies the principle of local quality by assigning unique mutation characteristics to specific tissue locations. Each tissue type's nucleic acids carry distinctive mutation signatures that reflect their local origin, enabling the system to maintain spatial localization information even when nucleic acids from multiple body parts are combined in distal samples.
Data Source
AI summary
Disclosed herein are methods for improving detection and monitoring of human diseases. The methods can be used to provide spatial and/or developmental localization of the source of each differential mutation within the body. The methods can also be used to generate a mutation map of a subject. And the mutation map can be used to monitoring state(s) of health of one or more tissues of a subject.