Nucleic Acid Basecalling via Spot Coordinate Mapping and Signal Correction
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Solution Overview
Problem
Existing nucleic acid sequencing methods face challenges in accurately determining base types due to optical effects, spatial effects, and chemical reactions during image acquisition and processing.
Innovation Solution
A method for calling bases in a nucleic acid by detecting images from sequencing, involving aligning spot coordinates, determining corrected signal intensity, and comparing it with preset values to determine base types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If optical imaging system is used to acquire images of base extension, then sequencing can be performed, but accurate basecalling becomes difficult due to optical effects, spatial effects, and chemical reactions affecting image acquisition, localization, and signal intensity
Solution Approach 1:
The patent applies preliminary action by constructing a spot set from images of at least one previous sequencing cycle before performing basecalling on the current cycle. This allows the system to pre-establish reference information about spot positions and signal characteristics from earlier cycles, which is then used to correct and improve the accuracy of basecalling in the current cycle, thereby resolving the accuracy issue while maintaining sequencing productivity
Solution Approach 2:
The patent implements feedback by using signal intensity information and spot position data from previously acquired sequencing images to inform and improve the basecalling process for the current image. The system continuously refines its basecalling accuracy by incorporating information from prior cycles, creating a feedback loop that progressively improves measurement precision without sacrificing sequencing throughput
2Measurement precision
If multiple images from different time points are correlated to determine nucleotide sequence, then basecalling accuracy can be improved, but processing complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the complex task of basecalling into distinct modules: image acquisition from multiple cycles, spot detection and coordinate extraction, spot set construction from previous cycles, signal intensity determination, and base type identification. This modular approach processes multiple images systematically, improving accuracy through correlated analysis while managing processing complexity through structured segmentation of the workflow
Solution Approach 2:
The patent reduces processing complexity by performing preliminary processing in earlier sequencing cycles. The spot set constructed from previous cycles contains pre-extracted and organized information about spot positions and characteristics that can be directly applied to current basecalling. This preliminary action avoids redundant processing when analyzing multiple images, thereby managing computational complexity while maintaining improved basecalling accuracy
Data Source
AI summary
A method for identifying a base in nucleic acid, a computer-readable storage medium, a computer program product, and a system. The method for identifying a base in nucleic acid comprises: mapping a coordinate of each bright spot in a bright spot set corresponding to a template onto an image to be inspected, and determining the position of a corresponding coordinate on said image (S11); determining the intensity of a signal at the position of the corresponding coordinate on said image, the intensity being a corrected intensity (S21); and comparing the intensity of the signal at the position of the corresponding coordinate on said image with the size of a first preset value, and determining a base type corresponding to the position on the basis of the comparison result, so as to achieve base calling (S31). The method may quickly and accurately identify a base, and achieve the determination of an order of nucleotides/bases of at least part of a sequence of a template.