Consensus Profile Generation for Single Nucleic Acid Sequencing
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Solution Overview
Problem
Current methods for analyzing nucleic acid molecules are inefficient in quickly and effectively extracting underlying genomic information, particularly for single molecules or groups of molecules with overlapping sequences.
Innovation Solution
A method involving binding marker molecules to nucleic acid molecules to generate detectable signals, acquiring and processing these signals to extract genomic information through a series of data processing steps, including outlier identification, registration, and consensus profile generation, using techniques like curve registration and functional data depth measures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If marker molecules are bound to single nucleic acid molecules to generate detectable signals, then genomic information can be extracted from single molecules, but the detectable signals contain noise and variability that reduce measurement precision
Solution Approach 1:
The patent combines detectable signals from multiple marker molecules bound to the same nucleic acid molecule to generate a consensus signal. By merging individual marker signals through statistical aggregation (e.g., median or mean calculation), the method enhances the reliability and precision of genomic information extraction while reducing the impact of individual marker variability and noise.
2Loss of information
If multiple marker molecules are used to increase signal coverage, then more genomic information can be obtained, but the complexity of data processing increases
Solution Approach 1:
The patent creates a consensus profile that serves as a representative copy of the underlying genomic sequence. By generating this consensus representation from multiple marker signals, the system captures complete genomic information while simplifying the data structure for downstream analysis, effectively reducing processing complexity without losing informational content.
Solution Approach 2:
The patent transforms raw marker signal data into standardized consensus profiles through parameter transformations such as normalization, filtering, and statistical aggregation. These parameter changes convert complex, variable marker signals into consistent, comparable genomic representations, reducing processing complexity while preserving essential information.
3Ease of operation
If traditional bulk nucleic acid analysis methods are used, then the analysis process is simpler, but they cannot provide information about single molecules or heterogeneous populations
Solution Approach 1:
The patent replaces traditional bulk biochemical analysis methods with a direct optical detection system using marker molecules that emit detectable signals. This substitution eliminates complex sample preparation and bulk processing steps, enabling rapid single-molecule analysis while maintaining operational simplicity through automated signal acquisition and consensus profile generation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables accurate and efficient extraction of genomic information from nucleic acid molecules, improving data analysis by reducing noise and enhancing the quality of signal profiles, thereby providing reliable insights into genomic sequences.
Implementation Method 1
binding at least a portion of each of a plurality of nucleic acid molecules with a plurality of fluorescent molecules, the plurality of fluorescent molecules providing a detectable fluorescence signal
Data Source
AI summary
Systems and methods for identifying sequence information from measurements made on single nucleic acid molecules are disclosed. The systems and methods can include binding portions of nucleic acid molecules with marker molecules, such as fluorescent molecules and/or intercalating molecules. The marker molecules provide a detectable signal that includes information about the underlying genomic information of the location on the nucleic acid molecule where a given marker molecule is bound. A profile of the detectable signal along a position of the nucleic acid is acquired for multiple different nucleic acid molecules. The PRIMR algorithm processes the data to provide a consensus profile from which a consensus underlying genomic information can be determined.