Repeat Sequencing Nucleic Acid Error Reduction
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Solution Overview
Problem
Current nucleic acid sequencing methods, such as sequencing-by-synthesis, face challenges in reducing sequencing errors and improving accuracy, particularly in repeat sequencing processes.
Innovation Solution
The method involves performing a first sequencing process on a nucleic acid template using a predetermined ordering of nucleotides and reagents, followed by a second sequencing process with a different ordering, and determining the sequence of bases using both results, utilizing a system with a processor and machine-readable memory to execute instructions for nucleic acid sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a single predetermined ordering of nucleotides and reagents is used in sequencing-by-synthesis, then the sequencing process is simple and fast, but sequencing errors increase and accuracy decreases
Solution Approach 1:
The patent applies periodic action by performing multiple sequencing runs with alternating reagent flow orderings (e.g., TACG repeated vs. TGAC repeated). This periodic alternation between different ordering patterns allows the system to capture sequence information from multiple perspectives, reducing errors associated with any single ordering while maintaining a systematic and manageable process complexity.
2Measurement precision
If repeat sequencing with different reagent flow orderings is performed, then sequencing accuracy improves, but the time required for sequencing increases
Solution Approach 1:
The patent employs preliminary action by pre-establishing multiple predetermined reagent flow orderings (such as TACG and TGAC patterns) before the sequencing process begins. These orderings are designed in advance to complement each other, allowing the system to perform repeat sequencing with different patterns without requiring real-time decision-making or complex reconfiguration, thus reducing the time penalty associated with repeat sequencing.
3Reliability
If multiple sequencing runs with different orderings are performed, then sequencing errors are reduced, but the complexity of data processing increases
Solution Approach 1:
The patent implements feedback by systematically comparing results from multiple sequencing runs performed with different reagent flow orderings. The system uses this comparative feedback to identify and correct sequencing errors, as errors that appear in one ordering but not in another can be flagged and resolved. This feedback mechanism improves reliability while keeping data processing complexity manageable through structured comparison protocols.
Data Source
AI summary
A method for sequencing a nucleic acid template includes: (a) performing a first sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a first predetermined ordering of nucleotides and/or reagents to obtain a first sequencing result; (b) after the first sequencing process, performing a second sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a second predetermined ordering of nucleotides and/or reagents to obtain a second sequencing result, the second predetermined ordering of nucleotides and/or reagents being different from the first predetermined ordering of nucleotides and/or reagents and at least one of the first and second predetermined orderings of nucleotides and/or reagents being designed for repeat sequencing; and (c) determining a sequence of bases corresponding to at least a portion of the nucleic acid template using both the first sequencing result and the second sequencing result.