DNA Storage Linkage Preservation via Chromatin Reassembly
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Solution Overview
Problem
Current methods for preserving DNA integrity during storage and transportation are inadequate, as they fail to effectively protect DNA from degradation, leading to fragmentation and loss of long-range information critical for genomic analysis.
Innovation Solution
The methods involve forming nucleic acid complexes with DNA binding moieties such as polypeptides, histones, or nanoparticles, followed by crosslinking and sequencing, which helps in preserving physical linkage information even after degradation, thereby maintaining the integrity of DNA during storage and transportation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If DNA is stored and transported under normal conditions, then storage and transportation are simple and economical, but DNA integrity deteriorates due to fragmentation and degradation
Solution Approach 1:
The patent introduces an intermediary substance (such as a protective coating or stabilizing agent) that mediates between the DNA and the harmful environmental factors. This intermediary layer protects the DNA from degradation during storage and transportation without requiring complex storage conditions, thus resolving the contradiction between maintaining DNA integrity and avoiding harmful environmental effects.
Solution Approach 2:
The patent employs parameter changes by modifying the physical or chemical state of DNA or its environment. For example, it may involve changing the molecular weight characteristics, concentration, or physical form of DNA samples, or altering storage parameters such as temperature and humidity conditions. These parameter changes enable DNA to maintain its integrity under simplified storage and transportation conditions, resolving the contradiction between reliability and environmental exposure.
2Duration of action of stationary object
If existing preservation methods are used, then some DNA decay is delayed, but physical linkage information is lost when fragmentation occurs
Solution Approach 1:
The patent applies preliminary action by performing protective measures before DNA fragmentation occurs. It involves pre-coating DNA samples with protective agents or pre-establishing stable molecular complexes that prevent fragmentation and preserve physical linkage information in advance. This preliminary protection ensures that even during extended storage periods, the DNA maintains its structural integrity and information content, resolving the contradiction between preservation duration and information retention.
3Ease of operation
If DNA samples are subjected to degradation conditions, then storage simplicity is maintained, but N50 values and physical linkage information decrease
Solution Approach 1:
The patent implements self-service by enabling DNA samples to protect themselves through inherent stabilization mechanisms. The DNA forms self-assembling protective structures or complexes with integrated stabilizing components, eliminating the need for external protective measures or complex storage protocols. This self-protecting mechanism maintains high N50 values and physical linkage information while keeping storage and operation simple, thus resolving the contradiction between ease of operation and manufacturing precision.
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 significantly increases the N50 values of nucleic acid fragments and assembled contigs/scaffolds, ensuring the preservation of physical linkage information and enabling more accurate genomic analysis and sequencing results.
Implementation Method 1
contacting the isolated DNA to a population of nucleic acid binding moieties to form at least one nucleic acid complex
Implementation Method 2
The nucleic acid sample is contacted to a crosslinking agent following contacting to the population of nucleic acid binding moieties
Implementation Method 3
Sequencing the sample comprises contacting the population of nucleic acid binding moieties to a protease
Data Source
AI summary
Disclosed herein are compositions, systems, kits and methods related to preserving physical linkage information of isolated DNA subject to DNA damage, and identifying a nucleic acid preservative. Physical linkage information and DNA integrity may be preserved by methods relating to reassembly of chromatin onto isolated DNA molecules so as to protect the nucleic acids, preserve physical linkage information, or size select molecules of interest. Nucleic acid compositions produced by methods disclosed herein are preserved so as to be analyzed, for example, by high throughput sequencing methods.