Nucleic Acid Sequencing Read Length Extension via Periodic Monomer Cycling
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Solution Overview
Problem
Current nucleic acid sequencing methods often result in shorter read lengths due to limitations in sequencing methodologies, such as homopolymer sequence stretches and chemical degradation, which hinder the accurate assembly of genomic sequences.
Innovation Solution
The method involves providing a sequencing reagent with multiple nucleotide monomers to a target nucleic acid, allowing for longer read lengths by extending the polynucleotide strand with multiple nucleotide incorporations in each cycle, and using subsequent reagents with different monomers to achieve sequence information at single-base resolution through repeated rounds of sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If traditional sequencing methodologies are used, then sequencing can be performed, but read lengths are limited due to homopolymer sequence stretches and chemical degradation
Solution Approach 1:
The patent segments the sequencing process into multiple independent cycles, each incorporating only one type of nucleotide monomer (A, C, G, or T) with a reversible terminator. This segmentation allows for systematic sequencing of homopolymer regions by processing each nucleotide type separately across multiple cycles, thereby extending read lengths while maintaining accuracy through repeated observation of the same incorporation events
Solution Approach 2:
The patent employs periodic action by repeatedly cycling through the same four nucleotide monomers in sequence across multiple sequencing cycles. Each cycle incorporates a specific nucleotide type if present in the template, and this periodic repetition allows for extended reading through homopolymer stretches by observing consistent incorporation patterns across multiple cycles
2Productivity
If sequencing is performed with limited read lengths, then sequencing runs can be completed, but assembly of genomic sequences becomes difficult
Solution Approach 1:
The patent performs preliminary action by extending the read length of individual sequencing reactions through multiple cycles of nucleotide incorporation. By obtaining longer contiguous sequence reads upfront, the subsequent assembly of genomic sequences becomes simpler and more accurate, as fewer fragments need to be assembled and overlapping regions are more extensive
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 extends read lengths, enabling more accurate genomic sequencing and reducing the challenges of assembling homopolymer regions, thereby improving the reliability and completeness of nucleic acid sequencing.
Implementation Method 1
providing a first sequencing reagent to a target nucleic acid in the presence of a polymerase, wherein the first sequencing reagent includes at least two different nucleotide monomers
Data Source
AI summary
A method of sequencing nucleic acids, which can include steps of contacting a substrate having spatially distinguishable features with a plurality of nucleic acids to seed a subset of the features, thereby generating a seeded subset; amplifying the nucleic acids in the seeded subset to form nucleic acid colonies; repeating the preceding steps to increase the number of seeded features, thereby generating an array of nucleic acid colonies; and sequencing the array of nucleic acid colonies.