Trace Reconstruction Handling Indeterminant Errors in DNA Sequencing
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Solution Overview
Problem
DNA-based storage systems face challenges in accurately retrieving digital data due to errors introduced during DNA synthesis and sequencing, particularly with 'bursty' errors that current techniques struggle to correct, leading to unusable sequence reads.
Innovation Solution
The implementation of techniques that identify and manage indeterminant errors in polynucleotide sequences by skipping over error-prone regions and using subsequent base calls to determine a consensus output sequence, allowing for the reconstruction of accurate DNA strands from noisy reads.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current decoding techniques are used to correct errors in DNA sequence reads, then substitution errors can be identified and corrected, but bursty errors (multiple errors in localized regions) cannot be corrected and render reads unusable
Solution Approach 1:
The patent segments the DNA sequence read into multiple candidate subsequences by identifying potential error regions. Each candidate subsequence represents a possible correct version of the original sequence, allowing the system to evaluate multiple hypotheses simultaneously rather than attempting to correct the entire read as a single unit.
Solution Approach 2:
The patent introduces a consensus sequence as an intermediary reference derived from multiple sequencing reads. This consensus sequence serves as a mediator to compare against candidate subsequences, enabling the identification of correct sequences even when individual reads contain bursty errors that would otherwise be uncorrectable.
2Measurement precision
If reads with bursty errors are discarded to maintain data quality, then accuracy of recovered data is preserved, but the number of usable reads decreases and data recovery efficiency is reduced
Solution Approach 1:
The patent converts the harmful effect of bursty errors into a beneficial process by using the error patterns themselves as indicators. The presence of bursty errors identifies regions where candidate subsequences should be generated and evaluated, transforming what would normally be discarded data into useful information for reconstruction.
Solution Approach 2:
The patent changes the evaluation parameter from binary acceptance/rejection of entire reads to a more nuanced approach where candidate subsequences within reads are individually evaluated. This parameter change allows the system to salvage useful information from reads that would traditionally be discarded due to containing bursty errors.
3Measurement precision
If multiple candidate subsequences are generated and evaluated to handle indeterminant errors, then accuracy of consensus sequence is improved, but computational complexity and processing time increase
Solution Approach 1:
The patent performs preliminary actions by pre-identifying error-prone regions and generating candidate subsequences before the main consensus building process. This preliminary segmentation organizes the computational work in advance, making the subsequent evaluation more efficient and manageable.
Solution Approach 2:
The patent applies partial action by focusing computational resources only on regions of the sequence where indeterminant errors are likely to occur, rather than uniformly processing the entire sequence. This selective approach generates candidate subsequences only where needed, reducing overall computational complexity while maintaining accuracy.
Data Source
AI summary
Polynucleotide sequencing generates multiple reads of a polynucleotide molecule. Many or all of the reads contain errors. Trace reconstruction takes multiple reads generated by a polynucleotide sequencer and uses those multiple reads to reconstruct accurately the nucleotide sequence of the polynucleotide molecule. Some reads may contain errors that cannot be corrected. Thus, there may be reads that can be used throughout their entire length and other reads that have indeterminant errors which cannot be corrected. Rather than discarding the entire read when an indeterminant error is found, the portion of the read with the error is skipped and the sequence of the read following the error is used to reconstruct the trace. The amount of the read skipped is determined by the location of subsequence after the error that matches a consensus sequence of the other reads. Analysis resumes at a location determined by the location of the match.