Multi-Species Nucleic Acid Sequencing via Hybridization Capture
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Solution Overview
Problem
Current whole genome and exome sequencing methods are costly and inefficient, particularly in capturing biomedically important variants, and struggle with high CG content regions and repetitive elements in genomes, failing to provide adequate and cost-effective sequencing.
Innovation Solution
A method involving specialized sequencing protocols that generate nucleic acid subsets using probes targeting human and non-human genomes, allowing for concurrent sequencing of human and non-human nucleic acids from a single biological sample, using hybridization reactions and alignment with reference sequences to identify sources and produce biomedical reports.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If whole genome and exome sequencing is performed using standard methods, then comprehensive genomic coverage is achieved, but cost increases and sequencing efficiency decreases
Solution Approach 1:
The invention segments the genomic sequencing task by dividing it into targeted regions of interest versus the rest of the genome. Capturing probes are designed to specifically bind to and enrich only the relevant genomic regions (e.g., cancer-associated genes, specific pathways), thereby segmenting the sequencing workload to improve efficiency while maintaining comprehensive coverage of biologically important areas.
Solution Approach 2:
The invention extracts and isolates specific genomic regions of interest from the entire genome using hybridization capture technology. By designing probes that selectively bind to target sequences, the method extracts only the relevant portions of DNA for sequencing, removing unnecessary genomic material that would consume sequencing capacity without contributing to biomedical insights.
2Measurement precision
If standard exome enrichment kits are used, then exomic regions are captured, but biomedically interesting non-exomic and exomic regions are missed
Solution Approach 1:
The invention creates a universal probe design platform that can target multiple types of genomic regions simultaneously - both exomic and non-exomic regions. The capture probe technology is designed to be flexible and adaptable, allowing researchers to construct custom probe sets that can enrich for coding regions, non-coding regulatory elements, structural variant regions, and other biomedically important sequences in a single assay, making the system multi-functional rather than limited to exomes only.
Solution Approach 2:
The invention applies local quality by allowing different regions of the genome to be captured with region-specific optimization. Probe designs can be tailored to account for local genomic characteristics such as GC content, repetitive element density, and mappability variations in different genomic contexts, ensuring high capture efficiency and sequencing quality for each specific region of interest rather than applying a uniform approach throughout the genome.
3Measurement precision
If whole genome sequencing is performed, then comprehensive genomic data is obtained, but regions with very high CG content (>70%) sequence poorly
Solution Approach 1:
The invention addresses high CG content regions by modifying sequencing parameters and probe design strategies specifically for these difficult-to-sequence regions. This may include using specialized probe chemistries, adjusting hybridization conditions, or employing multiple sequencing technologies with different strengths to overcome the inherent difficulties of capturing and sequencing high GC content regions, thereby improving both completeness and reliability.
4Measurement precision
If separate assays are used for human and non-human nucleic acid sequencing, then comprehensive multi-species analysis is achieved, but cost and complexity increase
Solution Approach 1:
The invention merges multiple sequencing assays into a single unified platform by designing a universal probe system that can simultaneously capture and sequence nucleic acids from multiple species including human and non-human pathogens. This consolidation eliminates the need for separate assay workflows, reducing complexity while maintaining the ability to accurately detect and analyze multiple species concurrently from a single clinical sample.
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 efficient and cost-effective sequencing of both human and non-human nucleic acids from a single sample, improving the detection of biomedically relevant variants and reducing the need for separate assays, while minimizing human DNA content to optimize sensitivity to microbial targets.
Implementation Method 1
generating a subset of nucleic acid molecules from the biological sample using a pool of nucleic acid probes... conducting one or more hybridization reactions
Data Source
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.