Codon Replacement via Location-Specific Probability Scores

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Solution Overview

Problem

Existing codon replacement strategies do not consider the location-specific usage of codons within a genome, leading to undesired effects on reproductive fitness of organisms, as they analyze codon usage bias genome-wide without regard to codon location or epistatic interactions.

Innovation Solution

The approach involves generating location-specific probability scores for synonymous codons and selecting replacement codons based on these scores to replace codons or k-mers, considering epistatic interactions and linkage disequilibrium to achieve desired reproductive fitness outcomes, such as codon optimization or de-optimization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If genome-wide codon usage analysis is used to identify preferred and un-preferred codons, then codon replacement can be performed, but the location-specific usage patterns and epistatic interactions are ignored leading to undesired effects on reproductive fitness

Engineering Contradiction:

Improvesimplicity of codon replacement methodVSAvoidaccuracy of reproductive fitness outcome

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The genome is segmented into distinct loci, and codon usage analysis is performed separately for each location rather than genome-wide. This allows location-specific preferred and un-preferred codons to be identified, capturing the positional heterogeneity of codon usage patterns while maintaining a systematic approach to codon replacement.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different codon replacement strategies are applied to different locations in the genome based on location-specific codon usage patterns. Each locus has its own set of preferred and un-preferred codons determined by local statistical analysis, allowing the method to account for epistatic interactions and positional effects on reproductive fitness.

Inventive Principle:

Principle #3Local quality

2Productivity

If synonymous codons are replaced without considering location-specific usage, then the process is simple and fast, but the desired effect on reproductive fitness may not be achieved

Engineering Contradiction:

Improvespeed of codon replacementVSAvoidprecision of fitness modification outcome

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

Before performing codon replacement, the method pre-calculates location-specific codon usage statistics and identifies preferred and un-preferred codons for each genomic position. This preliminary analysis creates a replacement map that guides subsequent codon substitutions, ensuring that each replacement is strategically chosen to achieve the desired fitness outcome while maintaining efficiency.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The method uses statistical feedback from observed codon usage patterns at each location to guide replacement decisions. By analyzing the frequency and distribution of synonymous codons at specific loci, the system adjusts replacement strategies to account for local evolutionary constraints and epistatic interactions, improving the reliability of fitness modification outcomes.

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS20230274791A1Codon de-optimization or optimization using genetic architecture

Publication Date: 2023.08.31 THE CHINESE UNIVERSITY OF HONG KONG

AI summary

Replacement codons for modifying a genetic sequence are selected based on genetic architecture of a genome. For example, a location-specific estimation of codon usage can be generated, and preferred or un-preferred codons for a particular location can be identified statistically. A codon at a particular location can be replaced by a more-preferred or less-preferred synonymous codon. These techniques can be extended to replacement of k-mers of arbitrary length k within a segment of length s, where s is at least equal to k.