Synchronous Sequencing Base Calling With Crosstalk And Phasing Correction
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Solution Overview
Problem
Existing base-calling software is inadequate for synchronous sequencing, failing to accurately recognize base combinations due to optical crosstalk and phasing interference, leading to inaccurate sequencing results.
Innovation Solution
A method and system for correcting base-calling results in synchronous sequencing, involving crosstalk and phasing corrections using regression models and machine learning, to improve accuracy and reduce sequencing time and costs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If synchronous sequencing is performed to improve sequencing throughput and reduce costs, then productivity increases, but measurement precision deteriorates due to optical crosstalk and phasing interference
Solution Approach 1:
The patent applies feedback by using the detected optical signals from synchronous sequencing as input to a base-calling algorithm that iteratively refines base recognition. The algorithm processes raw signal intensities, applies corrections for crosstalk and phasing, and generates base calls that feed back into the sequencing process for continuous improvement of accuracy while maintaining high throughput
Solution Approach 2:
The patent introduces an intermediary base-calling algorithm that acts as a mediator between the optical detection system and the final sequencing results. This intermediary layer processes raw signals, corrects for interference effects, and translates them into accurate base calls, thereby resolving the contradiction between maintaining signal intensity for throughput and eliminating crosstalk for precision
2Device complexity
If existing base-calling software is used for synchronous sequencing, then device complexity remains low, but manufacturing precision deteriorates due to inability to accurately recognize base combinations
Solution Approach 1:
The patent changes key parameters of the base-calling process by introducing correction factors for optical crosstalk and phasing effects. The algorithm modifies signal intensity parameters through mathematical corrections before base recognition, thereby improving accuracy without requiring complex hardware modifications. This allows existing sequencing devices to achieve higher precision through software-based parameter optimization
3Measurement precision
If crosstalk correction is applied to eliminate optical interference, then measurement precision improves, but device complexity increases due to additional correction parameters
Solution Approach 1:
The patent applies preliminary action by pre-calculating and storing crosstalk correction matrices and phasing correction parameters before the actual sequencing run. These correction parameters are determined in advance based on system characterization and are then applied during base-calling without adding real-time computational complexity. This allows precision improvement through correction while keeping the device operationally simple
Data Source
AI summary
Provided is a synchronous sequencing method, including: constructing a sequencing library for a nucleic acid sample to be tested; loading the sequencing library onto a sequencing chip; performing a plurality of synchronous sequencing reaction cycles on the sequencing library, wherein an image set generated in each of the plurality of synchronous sequencing reaction cycles constitutes a raw image set of the synchronous sequencing; acquiring a base-calling result of the synchronous sequencing based on the raw image set of the synchronous sequencing; correcting the signal intensity value of each base channel based on a predetermined correction parameter to obtain a corrected base-calling result; and determining a base output result of the synchronous sequencing based on the corrected base-calling result.