Nucleotide Sequence Synthesis Error Detection via Metric Segmentation
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Solution Overview
Problem
Existing nucleotide sequence manufacturing processes often result in errors, leading to discrepancies between synthesized nucleic acids and target sequences, which can be due to analytical or biological differences, and current methods lack efficient mechanisms to accurately detect and correct these errors.
Innovation Solution
A method and system that utilize unique molecular indices (UMIs) and processor chips to generate sequencing metrics, allowing for the detection of errors and adjustment of synthesis processes to reduce error rates, including the identification and removal of synthetic adapter sequences and calculation of mismatch rates, thereby improving the accuracy of nucleic acid sequencing and manufacturing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If nucleotide sequence manufacturing processes are used to synthesize nucleic acids, then productivity is improved, but manufacturing precision deteriorates due to errors arising in the manufacturing process
Solution Approach 1:
The patent segments the sequencing process into multiple independent metric evaluations (first metrics and second metrics) that can be applied systematically to sequence data structures. This segmentation allows for comprehensive error detection across different aspects of sequence synthesis without requiring a complete re-run of the manufacturing process, thus maintaining productivity while improving precision through targeted analysis.
Solution Approach 2:
The patent implements feedback mechanisms by generating metric scores from sequence data and using these scores to identify errors in the manufacturing process. The system continuously monitors synthesis quality through multiple metrics and uses this feedback information to detect and correct errors, thereby improving manufacturing precision while maintaining high productivity through automated quality control.
2Manufacturing precision
If multiple metrics are applied to sequence data structures to detect errors, then manufacturing precision is improved, but device complexity increases
Solution Approach 1:
The patent divides the complex metric evaluation system into distinct, modular components: first metrics that evaluate initial sequence data characteristics, and second metrics that evaluate additional characteristics such as unique molecular indices. This segmentation allows each metric to be independently developed, validated, and applied, reducing the overall complexity while maintaining comprehensive error detection capability.
Solution Approach 2:
The patent applies first metrics to sequence data structures before applying second metrics, creating a staged evaluation process. This preliminary action allows the system to quickly filter and assess basic sequence characteristics first, then proceed to more complex evaluations only when necessary, thereby improving error detection accuracy without requiring all complex metrics to be applied simultaneously, thus managing device complexity.
3Manufacturing precision
If unique molecular indices are used to detect and correct errors, then manufacturing precision is improved, but loss of time increases due to additional processing steps
Solution Approach 1:
The patent incorporates unique molecular indices into the sequence data structure during the initial manufacturing process, performing preliminary action to embed error-detection capabilities before synthesis is complete. This allows for rapid error identification and correction during metric evaluation without requiring additional time-consuming processing steps after manufacturing, thus improving precision while minimizing time loss.
Solution Approach 2:
The unique molecular indices enable the sequence data itself to serve as its own error-detection mechanism. The indices are inherently embedded in the manufactured nucleic acids and automatically provide error detection and correction information during metric evaluation, eliminating the need for separate, time-consuming verification processes and thereby improving precision without significant time penalty.
4Manufacturing precision
If synthetic adapter sequences are removed and unique molecular indices are merged, then manufacturing precision is improved, but device complexity increases
Solution Approach 1:
The patent extracts and removes synthetic adapter sequences from the sequence data structure as a distinct processing step. This extraction isolates the adapter sequences that can interfere with accurate mismatch rate calculations, allowing for cleaner, more precise error detection. By taking out these interfering elements, the system improves manufacturing precision without requiring complex algorithms to handle the interference, thus managing processing complexity.
Solution Approach 2:
The patent merges multiple unique molecular indices into a unified set after removing adapter sequences. This merging consolidates the error-detection information from multiple indices into a coherent dataset that can be efficiently evaluated by the metric system. By combining these indices after preliminary processing, the system improves mismatch rate calculation accuracy while avoiding the complexity of evaluating each index separately throughout the entire process.
Data Source
AI summary
Provided in one example is a system that includes one or more processors to receive a sequence data structure; apply at least one first metric of a plurality of metrics to the sequence data structure to generate at least one first metric score; determine that the at least one first metric score satisfies a first condition; apply, responsive to the at least one first metric score satisfying the first condition, at least one second metric of the plurality of metrics to the sequence data structure to generate at least one second metric score; and output an indication of the at least one first metric score and the at least one second metric score.