CGH Probe Evaluation Using Proximity Scores for CNV Resolution
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Solution Overview
Problem
Current Comparative Genomic Hybridization (CGH) methods using BAC clones have limitations in resolving smaller Copy Number Variations (CNVs) and targeting precise genomic regions due to the large size of BACs, which restricts the ability to accurately detect and analyze genomic alterations.
Innovation Solution
The development of methods to evaluate candidate CGH probe nucleic acid sequences using a proximity score, which involves identifying suitable probe sequences for specific genomic regions and determining their proximity score based on homology and distribution across the genome, to enhance the resolution and precision of CNV detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If BAC clones are used as CGH probes, then the assay can detect chromosomal alterations, but the resolution is insufficient to detect smaller CNVs due to the large size of BACs (over 100,000 bp)
Solution Approach 1:
The invention segments the large BAC clone probes into smaller polynucleotide probe sequences (typically 50-500 bp). This segmentation allows the probes to target specific regions within the larger BAC clone sequences, thereby improving the resolution of CNV detection while maintaining the ability to detect chromosomal alterations.
Solution Approach 2:
The invention applies local quality by designing polynucleotide probes with specific sequences that are complementary to particular genomic regions of interest. By selecting probes with optimized local sequence characteristics (homology, uniqueness, and specificity), the assay achieves higher resolution for detecting small CNVs in specific genomic locations.
2Manufacturing precision
If BAC clones are used as CGH probes, then chromosomal alterations can be detected, but the ability to target precisely defined regions is limited
Solution Approach 1:
The invention applies preliminary action by performing in silico analysis and selection of polynucleotide probe sequences before experimental implementation. Computational methods are used to pre-evaluate probe candidates based on criteria such as homology to target regions, uniqueness in the genome, and absence of repetitive sequences, thereby simplifying the subsequent experimental process and improving targeting precision.
Solution Approach 2:
The invention uses copying by creating multiple polynucleotide probe sequences that are complementary to the same target genomic region. These replicated probe sequences are then evaluated and selected based on their performance characteristics, allowing for optimized targeting of precisely defined genomic regions while managing design complexity through systematic replication and selection.
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 efficient identification of gene regions associated with diseases and therapeutic interventions by improving the resolution and specificity of CNV detection, enabling cost-effective and efficient analysis of genomic alterations.
Implementation Method 1
comparative genomic hybridization (CGH) methods, which utilize polynucleotide probes that are complementary to sequences of interest
Data Source
AI summary
Methods of evaluating candidate CGH probe nucleic acid sequences are provided. Aspects of the methods include providing a candidate CGH probe nucleic acid sequence for a target sequence of a copy number variation (CNV) of a genome. A proximity score is then determined for the candidate CGH probe nucleic acid sequence and employed to evaluate the sequence. Aspects of the invention further include computer programming and systems that include the same which are configured to evaluate candidate CGH probe nucleic acid sequences using a proximity score.