Single Label Comparative Hybridization for Genetic Abnormality Detection
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Solution Overview
Problem
Comparative genomic hybridization methods face challenges due to the need for different fluorescent labels, which complicate sample processing and result evaluation, especially when using two-color systems.
Innovation Solution
The method employs the same detectable label for both test and reference nucleic acids, allowing for selective cleavage or binding approaches to determine their relative amounts hybridized to a nucleic acid array, enabling the detection of chromosomal or genetic abnormalities without the need for multiple label readings.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If different fluorescent labels are used for test and reference nucleic acids in two-color comparative genomic hybridization, then the ability to detect chromosomal abnormalities is improved, but the complexity of sample processing and result evaluation increases
Solution Approach 1:
The patent uses the same fluorescent label for both test and reference nucleic acids, creating a homogeneous labeling system. This eliminates the need for separate detection channels and simplifies data analysis while maintaining the ability to distinguish between test and reference samples through other means such as spatial separation or temporal sequencing.
Solution Approach 2:
The patent extracts the distinguishing feature from the labeling system itself and separates it into a different domain (such as spatial positioning on the array or temporal ordering of hybridization). This allows the fluorescent labels to be identical while still enabling differentiation of test and reference samples through the extracted positional or temporal information.
2Reliability
If two-color fluorescent labeling is used for comparative hybridization, then chromosomal abnormalities can be detected, but data interpretation becomes more complex
Solution Approach 1:
By using identical fluorescent labels for both test and reference nucleic acids, the patent creates a homogeneous detection system that produces simpler, more uniform data. This homogeneity reduces the complexity of data interpretation while maintaining reliable detection of chromosomal abnormalities through the preserved signal intensity information.
Solution Approach 2:
The patent discards the approach of using different fluorescent colors to differentiate samples and recovers the differentiation capability through alternative means such as spatial positioning or temporal sequencing. This discarding of color differentiation simplifies the data interpretation process while recovering the essential function of sample distinction through other informative parameters.
3Adaptability or versatility
If multiple fluorescent labels are used in comparative genomic hybridization, then sample differentiation is improved, but the number of processing steps increases
Solution Approach 1:
The patent employs homogeneous fluorescent labeling where both test and reference nucleic acids use the same label. This reduces the number of processing steps required for differential detection while maintaining sample differentiation capability through spatial or temporal information, thereby improving processing efficiency without sacrificing adaptability.
Solution Approach 2:
The single fluorescent label system serves multiple functions: it labels both test and reference samples, provides detectable signal for quantification, and enables sample differentiation when combined with spatial or temporal information. This multi-functional approach eliminates the need for multiple specialized labels and their associated processing steps.
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 simplifies the detection process, enhances sensitivity, and improves the accuracy of identifying genetic abnormalities by using a single label for both samples, reducing the complexity of data interpretation and sample processing.
Implementation Method 1
comparative hybridization methods test the ability of two nucleic acids to interact with a third target nucleic acid
Data Source
AI summary
The present invention provides methods of detecting and mapping chromosomal or genetic abnormalities associated with various diseases or with predisposition to various diseases, or to detecting the phenomena of large scale copy number variants. In particular, the present invention provides advanced methods of performing array-based comparative hybridization that allow reproducibility between samples and enhanced sensitivity by using the same detectable label for both test sample and reference sample nucleic acids. Invention methods are useful for the detection or diagnosis of particular disease conditions such as cancer, and detecting predisposition to cancer based on detection of chromosomal or genetic abnormalities and gene expression level. Invention methods are also useful for the detection or diagnosis of hereditary genetic disorders or predisposition thereto, especially in prenatal samples. Moreover, invention methods are also useful for the detection or diagnosis of de novo genetic aberrations associated with post-natal developmental abnormalities.