Real-Time Sequencing By Incorporation Signal Processing

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Solution Overview

Problem

Current genetic analysis methods rely on fragmented data, such as SNPs, rather than the entire genetic code, limiting the depth of understanding and interpretation in medical diagnostics and treatment responses.

Innovation Solution

The development of computer-implemented processes for analyzing fluorescent signals from sequencing by incorporation systems to identify nucleotide base sequences in real-time, using pulse and signal processing techniques to distinguish incorporation events from noise, enabling the analysis of entire nucleic acid sequences.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If fragmented genetic data (SNPs) is used for analysis, then the analysis process is simpler and faster, but the depth of understanding and interpretation is limited

Engineering Contradiction:
Improveanalysis speedVSAvoidgenetic information completeness
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The patent segments the entire genetic sequence into individual bases that are sequentially identified through real-time sequencing. Each base incorporation event is detected and recorded, allowing the complete genetic code to be analyzed base by base rather than relying on pre-selected fragmented markers.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary sequencing of the entire genetic code before analysis, capturing all base sequences in real-time. This preliminary action of obtaining complete sequence data enables comprehensive downstream analysis without being limited to pre-chosen genetic markers.

Inventive Principle:
Principle #10Preliminary action

2Loss of information

If the entire genetic code is analyzed in real-time, then comprehensive genetic information is obtained, but the data processing complexity increases

Engineering Contradiction:
Improvegenetic information completenessVSAvoiddata processing complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The patent implements real-time feedback mechanisms where each detected base incorporation event immediately updates the sequence data. The system continuously monitors fluorescence signals, identifies incorporated bases, and builds the complete sequence in real-time, allowing dynamic adjustment and verification during the sequencing process.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent uses fluorescently labeled nucleotides as intermediaries to detect base incorporation events. Each nucleotide carries a fluorescent label that emits a detectable signal upon incorporation, serving as an intermediary between the biochemical reaction and the detection system, thereby simplifying the detection of complex genetic information.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If fluorescent signal analysis is performed to identify each base incorporation event, then accurate sequence data is obtained, but signal processing time and computational resources increase

Engineering Contradiction:
Improvebase identification accuracyVSAvoidsignal processing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs periodic detection cycles where fluorescence signals are monitored at regular intervals during nucleotide incorporation. Each cycle involves adding a nucleotide, detecting the fluorescent signal, and recording the base identity, creating a rhythmic sequence of actions that balances accuracy with processing efficiency.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent uses different fluorescent colors to represent different nucleotide bases. Each base (A, T, C, G) is labeled with a distinct fluorescent color, allowing rapid visual and computational identification of incorporated bases through color detection, thereby reducing the time and complexity of base identification.

Inventive Principle:
Principle #32Color changes

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 allows for more accurate and comprehensive analysis of genetic information, improving the interpretation of genetic data and enhancing the diagnosis and treatment of diseases by considering the entire genetic code, rather than just key signposts.

Implementation Method 1

The processes utilize fluorescent, or other detectable, label incorporation to identify the sequence of nucleotides in a template nucleic acid sequence

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2155855B1Methods and processes for calling bases in sequence by incorporation methods
Publication Date: 2016.10.12 PACIFIC BIOSCIENCES OF CALIFORNIA INC
  • EP2155855B1 patent drawingFigure 1
  • EP2155855B1 patent drawingFigure 2
  • EP2155855B1 patent drawingFigure 3

AI summary

Computer implemented methods, and systems performing such methods for processing signal data from analytical operations and systems, and particularly in processing signal data from sequence-by- incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof.