Real-Time Sequencing Prioritization via Unique Molecular Identifiers
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Solution Overview
Problem
Current nucleic acid sequencing technologies are costly and time-consuming, hindering quick pathogen identification and antibiotic susceptibility analysis, which can lead to suboptimal therapy decisions and secondary infections or patient deterioration.
Innovation Solution
A system and method for real-time prioritization of sequencing nucleic acid molecules from multiple sources using unique identifiers and a prioritization supervisor, allowing for dynamic control of sequencing processes such as continuation, pause, or termination based on predefined rules, enabling efficient sequencing of high-priority samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If next-generation sequencing is used for pathogen identification, then sequencing speed is improved, but sample preparation time and complexity increase
Solution Approach 1:
The patent applies preliminary action by pre-attaching unique molecular identifiers (UMIs) to nucleic acid molecules during sample preparation, before sequencing. This pre-tagging enables real-time identification and prioritization during sequencing without adding complexity to the sequencing process itself, resolving the contradiction between speed and preparation complexity.
Solution Approach 2:
The patent introduces UMIs as intermediary molecules that serve as mediators between the sample and sequencing process. These unique identifiers act as a bridge that enables real-time tracking and prioritization of molecules from different sources without requiring complex sample preparation protocols, thus improving speed while maintaining manageable complexity.
2Quantity of substance
If multiple samples are multiplexed through sequencing technology, then cost is reduced, but time between sample acquisition and pathogen identification increases
Solution Approach 1:
The patent implements feedback control by continuously monitoring sequencing data in real-time and using UMI identification to dynamically adjust sequencing priorities. High-priority samples (e.g., from critical patients) can be identified and prioritized during the sequencing run itself, ensuring rapid pathogen identification while still processing multiple samples through multiplexing, thus reducing time loss without sacrificing throughput.
Solution Approach 2:
The patent applies dynamics by enabling real-time reconfiguration of sequencing priorities based on identified sample characteristics and clinical urgency. The system can dynamically shift resources from lower-priority samples to high-priority samples during the sequencing run, maintaining efficient multiplexing while minimizing time to identification for critical cases.
3Reliability
If traditional microbiological procedures are used, then definitive pathogen identification is achieved, but time required is several days
Solution Approach 1:
The patent replaces traditional mechanical/cultural microbiological methods with molecular sequencing technology. By using UMI-tagged next-generation sequencing with real-time prioritization, the system achieves definitive pathogen identification through molecular analysis rather than cultural growth methods, dramatically reducing time from days to hours or minutes while maintaining or improving identification accuracy.
Solution Approach 2:
The patent applies preliminary action by pre-preparing samples with UMI tags and organizing them for rapid sequencing. This preliminary molecular tagging and organization enables immediate high-throughput sequencing and real-time analysis, replacing the lengthy traditional workflow while ensuring reliable pathogen identification through robust molecular methods.
Data Source
AI summary
A method for prioritizing sequencing of nucleic acid molecules from two or more sources, comprising: (i) ligating one or more ends of each of a plurality of nucleic acid molecules to an adapter, wherein the adaptor is unique to each source and comprises a unique identifier nucleic acid sequence; (ii) pooling the nucleic acid molecules from each of the two or more sources; (iii) sequencing a plurality of nucleotides of an identifier nucleic acid sequence of an adapter; (iv) determining in real-time from which of the two or more sources the nucleic acid molecule being sequenced came; (v) determining, from a prioritization rule set and based on the determined source, a sequencing priority for the nucleic acid molecule; and (vi) allowing the sequencing process to proceed, or modifying the sequencing process, based on the determined sequencing priority.