Sequencer Phasing Correction for Real-Time Base Calling
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Solution Overview
Problem
Phasing artifacts occur during nucleic acid sequencing due to synchronization loss among signals from multiple nucleic acid molecules within a cluster, leading to noise and reduced signal purity, which conventional methods address inefficiently and computationally intensively.
Innovation Solution
Implement real-time phasing correction methods using processor and memory configurations to determine corrected color values by retrieving partially phase-corrected values and applying prephasing corrections, reducing memory requirements and improving signal synchronization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional phasing correction methods are used, then signal synchronization is partially improved, but memory requirements increase and processing efficiency decreases
Solution Approach 1:
The patent applies preliminary phasing correction in advance using available data before full correction is possible. Specifically, it uses data from the current cycle and previously corrected cycles to perform preliminary correction, then refines it later when additional data becomes available. This allows the system to improve signal synchronization immediately without waiting for complete data collection, thereby reducing memory requirements while maintaining correction effectiveness.
Solution Approach 2:
The patent implements partial phasing correction using only the necessary subset of data required for immediate correction. Instead of storing and processing all possible historical data, it applies correction based on current cycle data and previously corrected results, performing just enough correction action needed at each step. This reduces memory complexity while still achieving reliable signal synchronization.
2Measurement precision
If real-time phasing correction is implemented, then base calling accuracy improves, but processing time and computational load increase
Solution Approach 1:
The patent performs preliminary phasing correction calculations using data available at each cycle before moving to the next cycle. By computing corrections in advance using current and previously corrected data, the system prepares correction values ready for immediate application, minimizing processing delays and maintaining real-time base calling accuracy without excessive computational overhead.
Solution Approach 2:
The patent maintains continuous phasing correction by iteratively applying corrections using data from the current cycle and previously corrected cycles. This continuous process ensures that base calling accuracy is maintained throughout the sequencing run without interruption, as each cycle builds upon the corrections from previous cycles, eliminating the need for batch processing and reducing overall processing time.
3Reliability
If multiple cycles of phasing correction are applied, then signal quality improves, but memory buffer requirements increase
Solution Approach 1:
The patent discards redundant historical data that is no longer needed for correction calculations and recovers memory space for continued sequencing. By using preliminary correction with current and previously corrected data, the system can discard older uncorrected data after it has served its purpose, thereby maintaining signal quality through multiple correction cycles while managing memory buffer capacity efficiently.
Solution Approach 2:
The patent applies partial phasing correction using only the minimal necessary historical data required for effective correction. Instead of retaining multiple full cycles of raw data in memory, it performs correction with the essential subset of data from current and previously corrected cycles, thereby improving signal quality through iterative correction while minimizing memory buffer requirements.
Data Source
AI summary
Methods determine corrected image data acquired by a nucleic acid sequencer during a cycle. Such methods may: (a) obtain an image of a substrate including a plurality of sites where nucleic acid bases are read; (b) measure color values of the plurality of sites from the image of the substrate; (c) store the color values in a processor buffer; (d) retrieve partially phase-corrected color values of the plurality of sites, where the partially phase-corrected color values were stored in the sequencer's memory during an immediately preceding base calling cycle; (e) determine a prephasing correction; and (f) determine the corrected color values. In implementations, these operations are all performed during a single base calling cycle. In embodiments, the methods additionally include using the corrected color values to make base calls for the plurality of sites.