Sequence Token Tagging for Genetic Variation Detection
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Solution Overview
Problem
Current techniques for determining nucleic acid sequences and genetic variations are inefficient and do not adequately address the rapid discovery of genetic or epigenetic variations, particularly requiring large-scale synthesis of probes and tags for known mutations or polymorphisms.
Innovation Solution
The method involves tagging nucleic acid sequence fragments with unique oligonucleotide tags or sequence tokens, allowing for efficient identification and determination of variations by dividing polynucleotides into non-overlapping segments and ligating unique sequence tokens to each segment, enabling the use of these tags for high-throughput screening and identification of rare alleles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If oligonucleotide tags or barcodes are used to represent target sequence information, then identification convenience and efficiency are improved, but the technique can only measure known mutations or polymorphisms and requires large-scale synthesis of probes and tags prior to application
Solution Approach 1:
The invention divides the oligonucleotide tag into multiple segments or modules, where each segment can independently hybridize to different regions of the target sequence. This segmentation allows the tag to detect both known and unknown variations by combining different segment configurations, thereby improving versatility while maintaining identification efficiency.
Solution Approach 2:
The invention introduces a new dimension of variability by using positional information and combinatorial arrangements of tag segments rather than relying solely on sequence identity. This dimensional expansion allows the same set of segments to represent multiple different genetic variations, enhancing adaptability without requiring proportional increases in tag diversity.
2Measurement precision
If large-scale synthesis of probes and tags is performed prior to application, then measurement of known mutations is improved, but time consumption and preparation complexity increase
Solution Approach 1:
The invention performs preliminary assembly of tag segments into modular units that can be stored and readily combined during the actual detection process. This preliminary preparation of building blocks maintains detection accuracy while significantly reducing the time and complexity of on-demand tag synthesis, as pre-synthesized segments can be quickly assembled rather than synthesizing complete tags from scratch.
Solution Approach 2:
The invention uses a small set of master tag segment sequences that can be repeatedly copied and recombined to generate the necessary detection tags. This copying approach reduces preparation time by avoiding large-scale de novo synthesis, as the same segment templates can be amplified and distributed across multiple detection applications while maintaining consistent detection precision.
3Productivity
If current techniques are used for determining nucleic acid sequences, then existing methods are applied, but rapid and efficient discovery of genetic or epigenetic variation is not adequately addressed
Solution Approach 1:
The invention designs oligonucleotide tags with universal binding capabilities that can detect multiple types of variations including SNPs, insertions, deletions, and epigenetic modifications through a single detection platform. This multi-functionality increases discovery productivity by eliminating the need for separate assays for different variation types while maintaining the ability to detect rare alleles through enhanced signal amplification and background reduction mechanisms.
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 the efficient tagging and identification of nucleic acid sequences, facilitating the detection of rare alleles and genetic variations within mixed populations, enhancing analytical assays in biomedical and industrial applications.
Implementation Method 1
selective and specific hybridization to complementary sequences on a microarray for a parallel readout of sequence information
Implementation Method 2
the dividing is by restriction enzyme digestion of the polynucleotides
Implementation Method 3
ligating a unique sequence token tag to each non-overlapping nucleic acid segment of each population of polynucleotides
Data Source
AI summary
The present invention provides methods and compositions for tagging nucleic acid sequence fragments, e.g., a set of nucleic acid sequence fragments from a single genome, with one or more unique members of a collection of oligonucleotide tags, or sequence tokens, which, in turn, can be identified using a variety of readout platforms. As a general rule, a given sequence token is used once and only once in any tag sequence. In addition, the present invention also provides methods for using the sequence tokens to efficiently determine variations in nucleotide sequences in the associated nucleic acid sequence fragments.