Multi-Species Nucleic Acid Probe Panels for Targeted Sequencing Coverage
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Solution Overview
Problem
Current whole genome and/or exome sequencing methods are costly and fail to capture biomedically important variants, particularly in regions with high CG content and repetitive elements, and do not provide adequate sequencing of non-exomic and exomic regions.
Innovation Solution
A method involving a pool of nucleic acid probes targeting human and non-human genomes, including probes for human V(D)J rearrangement and non-human sequences like human papilloma virus E6/E7 genes and bacterial 16S ribosomal RNA, followed by hybridization and sequencing to yield sequence information.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If standard whole genome or exome sequencing methods are used, then sequencing can be performed, but costly and fail to capture biomedically important variants in high CG content regions and repetitive elements
Solution Approach 1:
The patent applies local quality by designing specialized probes with different properties for different genomic regions. Specifically, it uses probes with modified chemical compositions and structures tailored for high CG content regions and repetitive elements, allowing each probe to optimize its binding properties for its specific target region rather than using a uniform probe design throughout the genome.
Solution Approach 2:
The patent employs composite materials by creating hybrid probe structures that combine different chemical moieties. The probes incorporate modified nucleic acid backbones, diverse chemical modifications, and composite structures that integrate multiple functional components to enhance binding affinity and specificity for difficult-to-sequence regions while maintaining overall sequencing capability.
2Adaptability or versatility
If exome enrichment kits are used, then exomic regions can be targeted, but biomedically interesting non-exomic and exomic regions are not captured
Solution Approach 1:
The patent implements universality by designing a multi-functional probe system that can simultaneously target multiple types of genomic regions including exomic, non-exomic, high CG content, and repetitive elements. The probe pool is constructed to perform multiple functions: capturing coding regions, capturing immune receptor rearrangements, capturing viral sequences, and capturing difficult genomic regions, all within a single sequencing assay.
Solution Approach 2:
The patent applies dynamics by creating an adaptable probe system that can be configured for different applications. The probe pool composition can be dynamically adjusted based on the specific biomedical question being asked, allowing the same basic platform to be optimized for cancer genomics, infectious disease, immunology, or other applications by modifying which probes are included or emphasized.
3Quantity of substance
If whole genome sequencing is performed, then comprehensive genomic data can be obtained, but inadequate and cost-effective sequencing of repetitive elements is achieved
Solution Approach 1:
The patent applies the extraction principle by selectively isolating and enriching specific genomic regions of interest from the complex whole genome. Instead of attempting to sequence the entire genome uniformly, the method extracts and concentrates signals from particular regions including repetitive elements, high CG content areas, and other medically important regions that would be difficult to detect in a standard whole genome sequencing approach.
Solution Approach 2:
The patent implements preliminary action by performing targeted enrichment of specific genomic regions before the actual sequencing step. The probe-based capture method pre-concentrates the DNA fragments from regions of interest, ensuring that these difficult-to-sequence regions are adequately represented in the sequencing library before the sequencing reaction occurs, thereby improving both efficiency and coverage.
4Measurement precision
If multiple separate assays are used for human and non-human sequences, then comprehensive detection can be achieved, but increased complexity and cost are incurred
Solution Approach 1:
The patent applies merging by combining multiple detection capabilities into a single unified assay. The probe pool integrates human-specific probes, non-human pathogen probes, and probes for other targets, allowing simultaneous detection of human genomic variants, viral sequences, bacterial sequences, and other elements in a single sequencing reaction, thereby reducing complexity while maintaining comprehensive detection accuracy.
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
Enables concurrent detection of human and non-human genetic data from a single sample, improving sequencing efficiency and coverage of medically relevant regions.
Implementation Method 1
generating the subset of nucleic acid molecules from the biological sample using a pool of nucleic acid probes
Data Source
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AI summary
Provided herein are compositions, methods, and systems for sample processing and/or data analysis. Sample processing may include nucleic acid sample processing and subsequent sequencing. Methods and systems of the present disclosure can be used, for example, for the analysis of a nucleic acid sample from a human, non-human, and combinations thereof.