Real-Time Sequencing Secondary Analysis with Iterative Alignment Paths
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Solution Overview
Problem
Existing DNA sequencing methods require sequential and time-consuming steps for variant identification after the sequencing process, which can be inefficient and laborious.
Innovation Solution
A system and method for performing real-time secondary analysis of nucleotide sequencing data by iteratively aligning sequence reads to a reference sequence using multiple alignment paths, including a more computationally efficient path for subsequent reads, allowing for real-time variant detection and reducing the need for extensive data transfer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If sequential alignment processing is used for all reads, then alignment accuracy is maintained, but processing time and computational resources increase significantly
Solution Approach 1:
The patent segments the alignment processing into two distinct paths: a first alignment path for initial reads that performs comprehensive alignment to establish accuracy, and a second alignment path for subsequent reads that leverages previously determined variant positions to skip redundant processing. This segmentation allows the system to maintain alignment accuracy for critical initial reads while significantly reducing processing time for the majority of subsequent reads.
Solution Approach 2:
The patent performs preliminary alignment processing on initial reads to identify variant positions and characteristics before processing subsequent reads. By determining variant positions in advance and storing this information, the system can use these preliminary results to guide and accelerate the alignment of subsequent reads, avoiding redundant computational steps while maintaining accuracy.
2Reliability
If comprehensive secondary analysis is performed on all sequencing data, then variant detection completeness is improved, but computational resource consumption increases
Solution Approach 1:
The patent applies partial action by performing comprehensive secondary analysis only on initial reads to establish variant positions, while applying a streamlined analysis approach to subsequent reads that focuses on verifying and refining variants near previously identified positions. This partial application of comprehensive analysis maintains variant detection completeness for critical regions while reducing overall computational resource consumption.
3Stability of the object's composition
If all sequence reads are processed through the same alignment path, then processing consistency is maintained, but processing efficiency decreases
Solution Approach 1:
The patent applies local quality by assigning different processing characteristics to different subsets of reads based on their position in the sequencing run and their relationship to identified variants. Initial reads receive comprehensive processing with full alignment scrutiny, while subsequent reads receive targeted processing focused on regions near known variants. This localized differentiation maintains processing consistency for each read type while significantly improving overall processing efficiency.
Data Source
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AI summary
Disclosed herein are systems and methods for performing secondary analyses of nucleotide sequencing data in a time-efficient manner. Some embodiments include performing a secondary analysis iteratively while sequence reads are generated by a sequencing system. Secondary analyses can encompass both alignment of sequence reads to a reference sequence (e.g., the human reference genome sequence) and utilization of this alignment to detect differences between a sample and the reference. Secondary analysis can enable detection of genetic differences, variant detection and genotyping, identification of single nucleotide polymorphisms (SNPs), small insertions and deletion (indels) and structural changes in the DNA, such as copy number variants (CNVs) and chromosomal rearrangements.