Nucleic Acid Physical Map Targeted Interrogation
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Solution Overview
Problem
Current optical physical mapping methods for long nucleic acid molecules offer high-throughput genomic analysis but lack resolution, while contact probe methods provide high resolution at low throughput, necessitating a method to combine these for targeted and precise interrogation of genomic regions without prior sequence knowledge.
Innovation Solution
A method involving partially immobilized nucleic acids on a substrate or open fluidic device, where optical interrogation generates a physical map to identify regions of interest (ROI) with corresponding coordinates, allowing a contact probe to precisely interrogate these regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If optical physical mapping methods are used for high-throughput genomic analysis, then throughput is improved, but resolution deteriorates
Solution Approach 1:
The method segments the genomic analysis process into two distinct phases: (1) optical mapping phase that processes many molecules at low resolution to identify candidate regions, and (2) contact probe phase that focuses on specific regions of interest at high resolution. This segmentation allows the system to achieve both high throughput and high resolution by applying different interrogation methods to different portions of the genome.
Solution Approach 2:
The optical mapping is performed as a preliminary action to generate a physical map and identify regions of interest before applying the contact probe method. This preliminary identification of candidate regions allows the subsequent high-resolution interrogation to focus only on relevant areas, maximizing the efficiency and resolution of the overall process.
2Measurement precision
If contact probe methods are used for high resolution interrogation, then resolution is improved, but throughput deteriorates
Solution Approach 1:
The method applies local quality by using the contact probe method only for specific regions of interest rather than for the entire genome. The optical map provides a broad overview, and the contact probe is directed only to locally identified candidate regions, thereby achieving high resolution where needed while maintaining overall throughput.
3Adaptability or versatility
If optical mapping is used without prior sequence knowledge, then adaptability is improved, but measurement precision deteriorates
Solution Approach 1:
The optical mapping serves as a preliminary action that creates a physical map based on higher-order nucleic acid structures without requiring prior sequence knowledge. This physical map then guides the contact probe to regions of interest, allowing the system to maintain adaptability to unknown sequences while achieving high resolution through the subsequent contact probe interrogation.
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
Enables rapid and precise identification and characterization of nucleic acid regions of interest with high resolution, combining the benefits of high-throughput optical mapping with the precision of contact probe analysis.
Implementation Method 1
optical interrogation generates a physical map to identify regions of interest (ROI) with corresponding coordinates
Implementation Method 2
further interrogating the ROI(s) by directing a contact probe to interrogate within the desired coordinates of the ROI(s)
Data Source
AI summary
Disclose herein are methods and devices for interrogating a region of interest within an immobilized nucleic acid molecule with a contact probe, where said region of interest is determined at least in part through an analysis of said molecule's physical map generated by optical interrogation.