Nucleic Acid Analysis With Cross-Linking for Spatial Context
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing polynucleotide sequencing methods fail to retain structural and molecular context of nucleic acids, losing important spatial and three-dimensional information during sample processing.
Innovation Solution
Methods involving separation of nucleic acid samples into discrete partitions while maintaining spatial proximity, using barcoding and cross-linking to attribute sequence reads to their original locations, allowing for sequencing that retains structural and molecular context.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If random fragmentation of polynucleotides is used for sequencing, then throughput and efficiency are improved, but structural and molecular context information is lost
Solution Approach 1:
The patent applies preliminary action by cross-linking spatially proximal nucleic acid segments before fragmentation and sequencing. This pre-establishes spatial relationship markers (cross-links) that allow reconstruction of structural context from otherwise randomized fragments, enabling both high throughput sequencing and retention of structural information
Solution Approach 2:
The patent uses cross-links as intermediary structures that mediate between the physical spatial arrangement of nucleic acids and the sequence data obtained after fragmentation. These cross-links serve as molecular markers that connect fragmented sequences back to their original spatial relationships, preventing loss of structural context
2Productivity
If sample processing techniques are applied to improve sequencing efficiency, then throughput increases, but three-dimensional structural information is lost
Solution Approach 1:
The method performs preliminary cross-linking of spatially adjacent nucleic acid segments before any processing that would disrupt three-dimensional structure. This establishes a molecular record of spatial relationships that persists through subsequent fragmentation and sequencing steps, enabling reconstruction of 3D structural information
Solution Approach 2:
The patent creates a molecular copy of spatial relationship information through cross-linking, where the cross-linked fragments serve as copies that encode the original three-dimensional arrangement. This copying mechanism allows the structural information to be preserved and reconstructed even after the original spatial configuration is disrupted by processing
Data Source
AI summary
The present invention is directed to methods, compositions and systems for analyzing sequence information while retaining structural and molecular context of that sequence information.