Optical Mapping for Genome-Wide Haplotype Sequences
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Solution Overview
Problem
Current optical mapping methods have not been used for generating genome-wide haplotype sequences, despite their effectiveness in creating genome-wide restriction maps for prokaryotic and eukaryotic genomes.
Innovation Solution
The use of optical mapping techniques to generate genome-wide probe maps, which can be analyzed in conjunction with genome-wide restriction maps to produce genome-wide haplotype sequences, employing detectable oligonucleotide probes with specific nucleotide patterns and hybridization protocols to determine probe locations and restriction sites.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical mapping methods are used to generate genome-wide restriction maps, then the ability to map restriction sites is improved, but the ability to generate haplotype sequences is insufficient
Solution Approach 1:
The patent applies universality by making the optical mapping system multi-functional. The same optical mapping infrastructure is used to generate both restriction maps and probe maps, which are then integrated to produce haplotype sequences. This allows a single system to perform multiple functions (restriction mapping, probe mapping, and haplotype assembly) that were previously required from separate methods
Solution Approach 2:
The patent merges restriction mapping data with probe mapping data to generate haplotype sequences. By combining these two types of mapping information in an integrated computational framework, the system overcomes the limitation of using either method alone, enabling haplotype sequence generation while maintaining restriction site mapping precision
2Measurement precision
If traditional sequencing methods are used to generate haplotype sequences, then sequence accuracy is improved, but the genome-wide coverage and efficiency are insufficient
Solution Approach 1:
The patent segments the genome into manageable units by using restriction enzymes to define restriction maps and oligonucleotide probes to define probe maps. These segmented maps are then assembled computationally to reconstruct genome-wide haplotype sequences, enabling efficient processing while maintaining accuracy
Solution Approach 2:
The patent replaces traditional mechanical sequencing approaches with an optical mapping-based system. Instead of using conventional sequencing chemistry and assembly, the system uses optical detection of restriction sites and probe hybridization positions, followed by computational integration, achieving both genome-wide coverage and high 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
This approach enables the generation of genome-wide haplotype sequences, allowing for the analysis of genomic variations and applications in disease prediction, diagnosis, and other biomedical and agricultural fields, while overcoming the limitations of existing methods.
Implementation Method 1
employing detectable oligonucleotide probes with specific nucleotide patterns and hybridization protocols to determine probe locations and restriction sites
Implementation Method 2
stained with a dye (e.g., a fluorescent dye). The restriction enzyme cleavage sites appear as breakages in the DNA under e.g., a fluorescent microscope
Data Source
AI summary
Methods, computer-accessible medium, and systems for generating a genome wide probe map and/or a genome wide haplotype sequence are provided. In particular, a genome wide probe map can be generated by obtaining a plurality of detectable oligonucleotide probes hybridized to at least one double stranded nucleic acid molecule cleaved with at least one restriction enzyme, and detecting the location of the detectable oligonucleotide probes. For example, genome wide haplotype sequence can be generated by analyzing at least one genome wide restriction map in conjunction with at least one genome wide probe map to determine distances between restriction sites of the genome wide restriction map(s) and locations of detectable oligonucleotide probes of the genome wide probe map(s) and defining a consensus map indicating restriction sites based on the genome wide restriction map(s) and/or locations of detectable oligonucleotide probes based on each of the genome wide probe map(s).