Error-Correcting Barcode Codewords for Multiplexed Sequencing Accuracy
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Solution Overview
Problem
Current sequencing technologies face challenges in efficiently preparing and identifying samples of high complexity, particularly in multiplexed sequencing where errors in barcode reading can lead to incorrect sample identification.
Innovation Solution
The method involves introducing nucleotides to a polynucleotide sample according to a predetermined order of nucleotide flows, obtaining signals, and resolving them to render a flowspace string that is a codeword of an error-correcting code. This code is designed to distinguish any codeword from others in the presence of zero, one, and two errors, facilitating accurate sample identification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional barcode reading methods are used in multiplexed sequencing, then sample identification can be performed, but errors in barcode reading lead to incorrect sample identification
Solution Approach 1:
The patent applies preliminary action by designing error-correcting codes in advance that can detect and correct errors before they lead to incorrect sample identification. The barcode sequences are pre-designed with error-correcting properties, allowing the system to anticipate and handle potential reading errors without compromising identification accuracy.
Solution Approach 2:
The patent implements feedback mechanisms through error-detecting and error-correcting codes that provide verification of barcode reading accuracy. The system uses checksums and validation algorithms to detect errors in real-time and correct them, ensuring that the final sample identification is accurate even if individual reading attempts contain errors.
2Productivity
If multiplexed sequencing is performed to increase throughput, then productivity improves, but the complexity of sample preparation and identification increases
Solution Approach 1:
The patent applies universality by designing a standardized error-correcting code system that can be applied across all multiplexed sequencing samples. The same barcode design principles and error-correction algorithms are universally applied to all samples in the multiplexed run, simplifying the overall process despite handling multiple samples simultaneously.
Solution Approach 2:
The patent uses parameter changes by modifying barcode sequence parameters to incorporate error-correcting features. The barcode sequences are designed with specific length, composition, and structural parameters that enable error detection and correction, allowing the system to maintain high throughput while managing complexity through optimized sequence parameters.
3Reliability
If error-correcting codes are implemented to improve barcode reading accuracy, then sample identification reliability improves, but the complexity of the coding system increases
Solution Approach 1:
The patent applies this principle by using simple, standardized error-correcting code structures that can be easily generated and processed. The error-correcting mechanisms use straightforward algorithms and data structures that, while adding some complexity, remain computationally efficient and easy to implement, comparable to using simple disposable components that are easy to replace and process.
Data Source
AI summary
A method for sequencing a polynucleotide sample having a barcode sequence includes: introducing a series of nucleotides to the polynucleotide sample according to a predetermined order of nucleotide flows; obtaining a series of signals resulting from the introducing of nucleotides to the polynucleotide sample; and resolving the series of signals over the barcode sequence to render a flowspace string, wherein the flowspace string is a codeword of an error-correcting code that is (i) designed based on and adapted for use with the predetermined order of nucleotide flows, and (ii) capable of distinguishing any codeword in the error-correcting code from the other codewords in the error-correcting code in the presence of zero, one, and two errors.