Synthetic Control Sequences for Nucleic Acid Sequencing Validation
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Solution Overview
Problem
Next-generation sequencing technologies face challenges with system noise and performance variation across sequencing processes, making it difficult to validate and normalize data sets over time, and requiring extensive resources and time for each sequencing run to determine instrument validity.
Innovation Solution
The use of deterministic synthetic control systems and beads with predefined nucleic acid sequences that produce predictable signals during sequencing, allowing for real-time monitoring and enhancement of instrument performance, and attribution of performance variation to instrument quality.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If next-generation sequencing technologies are used to increase throughput and reduce cost, then sequencing accessibility and information generation improve, but system noise and performance variation increase
Solution Approach 1:
The patent introduces control nucleic acid sequences as intermediary elements that mediate between the sequencing process and validation requirements. These control sequences are integrated into the sequencing library and serve as reference standards throughout the sequencing run, enabling real-time monitoring and validation without requiring separate validation processes.
Solution Approach 2:
The patent implements preliminary action by incorporating known control nucleic acid sequences into the sequencing library before the sequencing run begins. These control sequences are designed with predetermined characteristics that allow for pre-established validation criteria, enabling quality assessment during rather than after the sequencing process.
2Reliability
If control systems are designed for use before or after sequencing runs, then instrument validation can be performed, but time and materials are consumed for entire sequencing runs
Solution Approach 1:
The patent merges the validation function with the sequencing process by integrating control nucleic acid sequences directly into the sequencing library. This combination allows validation data to be collected simultaneously with sequencing data during the same run, eliminating the need for separate validation experiments and reducing overall time and material consumption.
3Reliability
If naturally occurring samples are used for evaluating noise and performance variation, then data for system evaluation can be obtained, but variation due to mutations and sequence differences occurs
Solution Approach 1:
The patent applies local quality by creating control nucleic acid sequences with specifically engineered uniform properties. Unlike naturally occurring samples that exhibit biological variation, these control sequences are synthetically designed to have consistent compositions and predetermined characteristics, providing stable reference points for evaluating system performance while maintaining the ability to assess noise and variation.
Data Source
AI summary
A system for performing quality control for nucleic acid sample sequencing is disclosed. The system comprises a set of solid supports, each solid support having attached thereto a plurality of nucleic acid sequences, wherein the set comprises plural groups of solid supports and each group contains solid supports having the same nucleic acid sequences attached thereto. The nucleic acid sequences of each group differ from each other. The nucleic acid sequences are synthetically derived, and the nucleic acids sequences are designed such that the nucleic acid sequences produce a predefined pattern of detectable signals during a sequencing run. A method of preparing a quality control for performing nucleic acid sample sequencing, a method of validating a nucleic acid sequencing instrument during a nucleic acid sequencing experiment, and a method of processing nucleic acid sequencing data during a nucleic acid sequencing experiment are also disclosed.