Nucleic Acid Sequencing Homopolymer Accuracy
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Solution Overview
Problem
Current nucleic acid sequencing methods face challenges in accurately sequencing genomic regions with homopolymer repeats or other repeating sequences, leading to inefficiencies and inaccuracies, particularly in determining the length of long repeating regions.
Innovation Solution
A method involving two distinct assays, one for generating a nucleic acid sequence and another for determining homopolymer sequences, with a programmed computer combining the data sets to achieve high accuracy, typically above 90%, using targeted probes and hybridization techniques to improve sequencing accuracy in difficult regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional sequencing methods are used, then general sequencing coverage is achieved, but accuracy in homopolymer and repeating regions deteriorates
Solution Approach 1:
The patent divides the sequencing task into two separate assays: a first assay for general nucleic acid sequencing and a second assay specifically targeted at homopolymer and repeating regions. This segmentation allows each assay to be optimized for its specific purpose, with the second assay using specialized probes and conditions to accurately determine lengths of repeating sequences that are difficult for conventional methods.
Solution Approach 2:
The patent introduces a second targeted assay as an intermediary step to resolve the ambiguity in homopolymer regions. This second assay uses specifically designed probes that hybridize to repeating sequences and provide additional data to disambiguate the first assay's results in difficult-to-sequence regions, thereby improving overall accuracy.
2Ease of manufacture
If a single sequencing assay is used, then process simplicity is maintained, but sequencing accuracy in difficult regions deteriorates
Solution Approach 1:
The patent segments the sequencing process into two distinct assays with different objectives and methodologies. The first assay provides general sequence information while the second assay specifically targets homopolymer and repeating regions with specialized probes and hybridization conditions, allowing each to be optimized independently.
Solution Approach 2:
The patent merges the results from two separate assays into a unified, high-confidence sequence determination. By combining the general sequencing data from the first assay with the specialized homopolymer data from the second assay, the method achieves superior accuracy in difficult regions while maintaining overall process efficiency.
3Productivity
If conventional single-assay methods are used, then time efficiency is maintained, but accuracy in determining repeating sequence lengths deteriorates
Solution Approach 1:
The patent performs preliminary sequencing with the first assay to obtain general sequence information, then uses this information to guide the second targeted assay. The second assay is designed based on predicted homopolymer regions from the first assay, allowing for focused and efficient determination of repeating sequence lengths without requiring complete re-sequencing.
Solution Approach 2:
The patent implements a feedback mechanism where the results from the first assay inform the design and execution of the second assay. Regions identified as potential homopolymers or repeating sequences in the first assay trigger targeted probing in the second assay, creating an iterative process that improves accuracy while maintaining efficiency.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enhances the accuracy and efficiency of sequencing homopolymer and other repeating regions, improving the overall sequencing process by providing reliable length determination and sequence identification.
Implementation Method 1
using targeted probes and hybridization techniques to improve sequencing accuracy in difficult regions
Data Source
AI summary
The present disclosure provides methods and systems for sequencing nucleic acid molecules in a manner that enables higher sequencing accuracy. Methods and systems provided herein may enable sequences that may have low-accuracy reads, such as homopolymer sequences or other repeating sequences, to be determined at a higher accuracy and efficiency.