DNA Sequence Recovery Using Probe Map Alignment
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Solution Overview
Problem
Conventional DNA sequencing methods, such as Sequencing-By-Hybridization (SBH), face challenges in accurate DNA sequencing due to probes not hybridizing correctly, leading to imperfect matches and incomplete recovery of target sequences, especially at polymorphic sites, and fail to consider both directional base sequence orders.
Innovation Solution
A method and apparatus that align probes with a base sequence of a predetermined length onto a target sequence, using a probe map generated from hybridization results, to determine representative values for each aligned position, and recover the target sequence by considering both directions and generating multiple sequence candidates to account for positional errors and polymorphisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional Sequencing-By-Hybridization (SBH) methods are used, then DNA sequencing can be performed, but accurate DNA sequencing cannot be achieved due to probes not hybridizing correctly
Solution Approach 1:
The patent applies partial action by using a subset of probes that show consistent hybridization patterns rather than requiring all probes to hybridize perfectly. By selecting probes that hybridize correctly at most positions and using statistical analysis to identify consistent patterns, the method achieves accurate sequencing without requiring perfect hybridization from every probe, thus resolving the contradiction between sequencing accuracy and hybridization reliability
Solution Approach 2:
The patent implements feedback through iterative refinement of sequence recovery. The system analyzes hybridization results, identifies consistent patterns across multiple probes, refines the recovered sequence, and uses this refined sequence to guide further probe alignment and analysis. This feedback loop allows the system to overcome individual probe hybridization errors and achieve high sequencing accuracy
2Loss of information
If probes are used for DNA sequencing, then base sequence information can be obtained, but incomplete recovery of target sequences occurs at polymorphic sites
Solution Approach 1:
The patent applies local quality by treating different regions of the target sequence differently based on their characteristics. At polymorphic sites where probes may not hybridize consistently, the system uses statistical analysis to identify patterns across multiple probes and applies local refinement algorithms. This allows the system to recover complete sequence information at polymorphic sites without requiring uniform probe behavior across the entire sequence
Solution Approach 2:
The patent changes parameters by using statistical distributions and representative values to describe probe alignment positions rather than requiring exact matches. By transforming the problem from exact probe-target matching to statistical pattern recognition, the system can recover complete sequence information even when individual probes show variability at polymorphic sites
3Measurement precision
If conventional SBH methods are used, then DNA sequencing can be performed, but both directional base sequence orders are not considered
Solution Approach 1:
The patent applies asymmetry by analyzing probe hybridization in both forward and reverse directions independently. Rather than assuming a single directional approach, the system examines alignment patterns from both 5' to 3' and 3' to 5' directions, allowing it to determine the correct base sequence order by comparing results from both directions. This asymmetric analysis resolves the contradiction by providing more comprehensive information without excessive complexity
4Measurement precision
If multiple probes are used to improve sequencing accuracy, then more positional errors and mismatches occur, but this is not adequately addressed
Solution Approach 1:
The patent uses partial action by selecting only the subset of probes that show consistent hybridization patterns across multiple alignments. Rather than using all probes equally, the system identifies probes with representative alignment positions and uses primarily those for sequence recovery. This selective approach maintains high sequencing accuracy while minimizing the impact of positional errors from inconsistent probes
Solution Approach 2:
The patent applies copying by creating multiple candidate sequences based on different probe alignment interpretations and then selecting the most likely correct sequence. The system generates several possible sequence reconstructions from the probe data, compares them against expected patterns, and selects the best match. This copying and comparison approach resolves positional ambiguities and maintains high alignment 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
This approach enhances the accuracy and efficiency of DNA sequencing by minimizing positional errors, accurately recovering target sequences even at mismatched positions and polymorphic sites, and considering both directional base sequence orders, resulting in a more precise and complete DNA sequence recovery.
Implementation Method 1
aligning a probe having a base sequence of a predetermined length onto a target sequence based on a result in which the probe is hybridized in the target sequence
Data Source
AI summary
A method of recovering a nucleic acid sequence using a probe map includes: aligning a probe onto a target sequence based on a result in which the probe is hybridized to the target sequence; determining a representative value representing each aligned position of the probe; and recovering a base sequence of the target sequence by using a probe map to which the determined representative values and base sequence information of the probe are mapped.