Bicycle Gene Identification via Structural Classification

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods struggle to identify highly divergent bicycle gene homologs due to their extreme sequence divergence, which limits functional inferences and evolutionary studies.

Innovation Solution

A sequence-independent method using a logistic regression classifier based on gene structure features, such as exon sizes and intron positions, to identify bicycle genes without relying on sequence similarity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sequence-search methods are used to identify homologous genes, then identification process is simple and fast, but highly divergent bicycle gene homologs cannot be detected due to extreme sequence divergence

Engineering Contradiction:
Improvedetection accuracy of bicycle gene homologsVSAvoidcomplexity of identification method
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces sequence-based identification methods with a gene structure-based classification system. Instead of using sequence similarity (the mechanical system of sequence searching), the invention uses structural features such as exon-intron architecture, gene length distributions, and synteny patterns to identify bicycle genes. This substitution allows detection of highly divergent homologs that sequence methods miss, as the structural features are conserved even when sequences diverge significantly.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the identification parameters from sequence similarity metrics (e.g., BLAST E-values, identity percentages) to structural parameters (e.g., exon count, intron positions, gene length ranges). By transforming the detection space from sequence domain to structural domain, the method can identify bicycle genes across distant taxa where sequence divergence would traditionally prevent detection.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If sequence divergence is high in bicycle genes, then functional adaptation and evolutionary innovation are enhanced, but homology detection becomes undetectable by conventional methods

Engineering Contradiction:
Improvefunctional adaptability of bicycle genesVSAvoiddetectability of homologous sequences
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent inverts the traditional homology detection approach. Instead of asking 'do these sequences look similar?' and concluding 'not homologous' when they don't, the method asks 'do these genes share conserved structural features?' and identifies homologs based on structural homology rather than sequence homology. This inversion allows detection of bicycle gene homologs that have diverged so much in sequence that conventional methods would reject them, while the structural conservation confirms their homological relationship.

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

3Measurement precision

If gene structure features are used for identification, then detection of divergent homologs is improved, but the identification process becomes more complex and time-consuming

Engineering Contradiction:
Improveprecision of bicycle gene identificationVSAvoidtime required for gene identification
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary classification of genes into categories (e.g., unicycles, bicycles, tricycles, megacycles) based on structural features before detailed analysis. By pre-sorting genes into structural categories using rules such as exon count thresholds, intron position patterns, and gene length ranges, the method rapidly identifies potential bicycle gene candidates without needing to exhaustively search all possible sequence alignments. This preliminary structural triage significantly reduces the time required for comprehensive homology detection.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS20250034654A1Identification of bicycle genes
Publication Date: 2025.01.30 HOWARD HUGHES MEDICAL INST
  • US20250034654A1 patent drawing
  • US20250034654A1 patent drawing
  • US20250034654A1 patent drawing

AI summary

A method of identifying a bicycle gene involves determining for a candidate gene a series of gene structure-based predictor variables, and applying a bicycle gene classifier including the predictor variables to determine whether the candidate gene is identified as a bicycle gene. The gene structure-based predictor variables can be selected from the following: (i) total gene length (base pair, bp); (ii) total length (bp) of coding exons; (iii) first coding exon length (bp); (iv) last coding exon length (bp); (v) number of internal exons in phase 0); (vi) number of internal exons in phase 1; (vii) number of internal exons in phase 2; and (viii) mean internal exon length (bp).