Targeted Genomic Sequencing via Selective Amplification
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Solution Overview
Problem
Current genome sequencing technologies are economically unfeasible for de novo sequencing and struggle to accurately characterize 5-10% of the human genome, particularly regions with structural features resistant to characterization, such as heterochromatic gaps near centromeres and the HLA complex.
Innovation Solution
A method involving targeted coverage of selected genomic regions through selective amplification and barcoding, allowing for de novo sequence assembly and high-throughput re-sequencing of remaining regions with high accuracy, using techniques like PCR amplification and barcoding to achieve deep coverage and retain molecular context.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If de novo sequencing of the entire genome is performed, then complete genome assembly is achieved, but the cost becomes economically unfeasible
Solution Approach 1:
The genome is divided into two categories: well-characterized regions and poorly characterized regions. The invention applies different sequencing strategies to each segment - targeted deep sequencing for poorly characterized regions and re-sequencing for well-characterized regions, making the overall process economically feasible while maintaining complete genome assembly
Solution Approach 2:
The invention applies different sequencing depths and methods to different genomic regions based on their characterization status. Poorly characterized regions receive targeted deep sequencing (100x-5000x coverage) while well-characterized regions undergo standard re-sequencing, optimizing resource allocation and cost efficiency
2Productivity
If standard sequencing technologies are used, then high throughput is achieved, but accuracy in characterizing structurally complex regions deteriorates
Solution Approach 1:
The invention performs preliminary identification of poorly characterized genomic regions using reference genome comparison. This preliminary action enables targeted enrichment and deep sequencing of specific regions that require high accuracy, while maintaining high throughput for the remainder of the genome through standard re-sequencing methods
Solution Approach 2:
The invention applies excessive sequencing depth (100x-5000x coverage) specifically to poorly characterized regions rather than uniformly across the entire genome. This partial application of excessive action ensures high accuracy for structurally complex regions while maintaining overall high throughput and cost efficiency
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 de novo sequencing of poorly characterized regions while maintaining molecular context, providing sufficient sequence information for assembly and retaining high accuracy across the genome.
Implementation Method 1
amplifying selected portions of at least some of the individual nucleic acid molecules in the discrete partitions to form a population of amplicons
Data Source
AI summary
The present invention is directed to methods, compositions and systems for analyzing sequence information from targeted regions of a genome. Such targeted regions may include regions of the genome that are poorly characterized, highly polymorphic, or divergent from reference genome sequences.