miRNA Base-Substitution Ratios for Stable Disease Identification
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Solution Overview
Problem
Existing methods for identifying diseases using miRNA as biomarkers in body fluids face variability and instability in test performance due to differences between specimens, leading to unreliable results.
Innovation Solution
A method involving the use of reference sequences with single base substitution sites to calculate a ratio (R) of specific short-chain nucleic acids in a sample, comparing this ratio to a threshold value to determine the presence or risk of a disease, utilizing techniques like next-generation sequencing to decode RNA sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If miRNA amount or concentration is used as an index for disease identification, then the test can be performed using easily collected body fluids, but the test performance becomes unstable due to variation between specimens and data sets
Solution Approach 1:
The invention changes the parameter from absolute miRNA amount/concentration to the ratio of miRNA sequences with different base substitutions at specific positions. This relative measurement approach normalizes variations between specimens and data sets, thereby stabilizing test performance while maintaining the ease of using body fluid samples.
2Ease of manufacture
If miRNA amount or concentration is used for disease identification, then the test can be performed with available technology, but measurement precision is insufficient due to increased variation between data sets
Solution Approach 1:
The invention transforms the measurement parameter from absolute miRNA quantity to the ratio of sequences with specific base substitutions. This parameter transformation reduces measurement variation and improves precision while keeping the test method accessible with current sequencing technology.
Solution Approach 2:
The invention replaces direct quantitative measurement of miRNA amount with sequence-based identification using next-generation sequencing. This substitution from mechanical/chemical quantification to molecular sequencing enables more precise and consistent measurements.
3Measurement precision
If single base substitution sites are used as biomarkers, then disease identification accuracy is improved, but the complexity of sequence analysis increases
Solution Approach 1:
The invention segments the miRNA sequence analysis by focusing on specific base substitution positions rather than analyzing the entire sequence. This segmentation approach simplifies the analysis complexity while maintaining high accuracy for disease identification.
Solution Approach 2:
The invention applies local quality by concentrating on specific positions in the miRNA sequence where base substitutions occur, rather than treating the entire sequence uniformly. This localized analysis reduces computational complexity while preserving diagnostic accuracy.
Data Source
AI summary
A sample identification method according to an embodiment includes setting a first reference sequence that includes a first sequence having a single base substitution site, the single base substitution site being a first base, and a corresponding second reference sequence, outputting the number of first short-chain nucleic acids having the first reference sequence and the number of second short-chain nucleic acids having the second reference sequence, calculating a ratio, obtaining a magnitude relationship between the ratio and a threshold value, and determining, from the number of sequences in which the ratio is greater than the threshold value, whether a subject from whom the sample is derived has the disease or at risk of developing the disease.


