MicroRNA Identification via Genomic Subsequence Alignment

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Solution Overview

Problem

Current methods for characterizing microRNAs from next-generation sequencing reads are inefficient due to short read lengths and the complexity of RNA folding analysis, leading to high computational demands and reduced accuracy, especially when dealing with star-miRNAs and genome-level applications.

Innovation Solution

A computer-implemented method that screens genomic neighborhoods for alignments with both the nucleic acid sequence and its reverse complementary, allowing for alignments with up to 0.6L errors within a 3000-nucleotide region, significantly reducing computational time while maintaining specificity and selectivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sophisticated pipelines with RNA folding analysis are used to identify miRNAs, then measurement precision is improved, but computing time increases significantly

Engineering Contradiction:
ImprovemiRNA identification accuracyVSAvoidcomputing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The method segments the genomic sequence into multiple subsequences and processes each subsequence independently for alignment. This divides the large-scale genome-level analysis into smaller, manageable units that can be processed faster while maintaining overall identification accuracy

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The method extracts only the essential alignment information from genomic subsequences without performing complete RNA folding analysis on the entire genome. By taking out and analyzing only relevant regions that contain potential miRNA candidates, the computing time is reduced while preserving measurement precision

Inventive Principle:
Principle #2Taking out (Extraction)

2Adaptability or versatility

If genome-level RNA folding analysis is performed, then miRNA detection coverage is improved, but device complexity increases

Engineering Contradiction:
Improvegenome-level detection coverageVSAvoidanalysis pipeline complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The genomic sequence is segmented into multiple subsequences that are processed independently. This segmentation enables genome-level coverage without requiring complex orchestration of entire-genome analysis, thereby reducing device complexity while maintaining detection coverage

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Instead of performing RNA folding analysis on the entire genome and then identifying miRNAs, the method inverts the approach by first identifying candidate regions through alignment and then performing focused analysis. This inversion simplifies the analysis pipeline while maintaining genome-level detection capability

Inventive Principle:
Principle #13The other way round (Inversion)

3Measurement precision

If multiple alignment checks including star-miRNA verification are performed, then measurement precision is improved, but productivity decreases

Engineering Contradiction:
ImprovemiRNA and star-miRNA identification accuracyVSAvoidanalysis throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The method performs preliminary alignment checks against multiple subsequences before conducting more rigorous verification steps. By establishing candidate regions early through efficient alignment, subsequent precision checks are performed only on relevant candidates, maintaining measurement precision while improving overall productivity

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3185157B1Computer-implemented method for the identification of micrornas
Publication Date: 2020.07.08 BIOFACET SAS
  • EP3185157B1 patent drawingFigure 1
  • EP3185157B1 patent drawingFigure 2
  • EP3185157B1 patent drawingFigure 3

AI summary

The present invention relates to a computer-implemented method for determining if a nucleic acid sequence belongs to a microRNA (miRNA) candidate encoded by at least one known genomic sequence, comprising: a) determining if the nucleic acid sequence or the reverse complementary sequence thereof can fully align with a first subsequence of the known genomic sequence; b) then, - if the nucleic acid sequence fully aligns with the first subsequence of the known genomic sequence, determining if the reverse complementary sequence of the nucleic acid sequence can align with a second subsequence of the known genomic sequence with X error(s) at the most, or - if the reverse complementary nucleic acid sequence of the nucleic acid sequence fully aligns with the first subsequence of the known genomic sequence, determining if the nucleic acid sequence can align with a second subsequence of the known genomic sequence with X error(s) at the most; wherein X is an integer from 0 to 0.4L, wherein L is the length of the nucleic acid sequence, and a third subsequence of the known genomic sequence which consists of the first and second subsequences and of the portion of the known genomic sequence between the first and second subsequences has a length T, wherein T ≤ 3000 nucleotides; c) whereby, if conditions a) and b) are met, the nucleic acid sequence is determined to belong to a miRNA candidate. The method uses less computer power than the commonly used methods based on hairpin folding.