Genomic Codon Mutability Estimation for Rapid Therapeutic Targeting
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Solution Overview
Problem
Current methods for developing therapeutic strategies against viral pathogens, such as novel antiviral drugs and vaccines, face delays due to the need for extensive sequence data from ancestral viruses, making it difficult to rapidly identify effective targets for novel viruses that could cause pandemics.
Innovation Solution
A method and system for estimating the mutability of genomic codons in a reference genomic sequence by calculating an importance value based on the codon's frequency of occurrence and spatial distribution, particularly near coding region boundaries, allowing for the rapid identification of conserved segments that are less likely to mutate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If pairwise alignment between predecessor and descendant sequences is performed to characterize viral mutations, then the accuracy of mutation characterization is improved, but the time required for therapeutic development increases significantly
Solution Approach 1:
The patent performs preliminary analysis of the ancestral viral genome to identify conserved segments before any descendant sequences are available. By calculating a conservedness score based on the frequency and distribution of codons within the ancestral sequence itself, the system prepares therapeutic targets in advance, eliminating the waiting period for sequence collection and alignment.
Solution Approach 2:
The patent extracts only the essential information needed for target identification directly from the ancestral sequence - specifically the frequency and spatial distribution of codons. This extraction approach bypasses the need for extensive sequence alignment and mutation characterization, obtaining the critical conservedness data from a single ancestral genome rather than requiring multiple descendant sequences.
2Reliability
If extensive sequence data from ancestral viruses is collected to identify conserved segments, then the reliability of therapeutic targets is improved, but the speed of response to novel viruses deteriorates
Solution Approach 1:
The ancestral viral genome serves itself as the source of information for identifying conserved segments. The system analyzes the frequency and distribution patterns of codons within the ancestral sequence itself, without requiring external descendant sequences. This self-service approach provides reliable conservedness scoring immediately upon obtaining the ancestral genome, enabling rapid response while maintaining target reliability.
Solution Approach 2:
The system performs the conservedness analysis as a preliminary action on the ancestral sequence before any outbreak response is needed. By pre-calculating conservedness scores based on codon frequency and distribution, the system has therapeutic targets ready when a novel virus emerges, eliminating the delay between virus identification and target selection.
3Measurement precision
If mutation information is extracted from mutational changes in other virus family members, then the accuracy of mutability estimation is improved, but the applicability to novel viruses deteriorates
Solution Approach 1:
The patent develops a universal method for estimating codon mutability that works for any viral genome, including novel viruses. The approach uses the frequency and distribution of codons in the ancestral sequence to calculate a conservedness score that predicts mutability. This universal approach does not depend on having previously observed mutations in related viruses, making it applicable to entirely novel viral families while maintaining estimation accuracy.
Solution Approach 2:
The system performs preliminary estimation of codon mutability directly from the ancestral sequence characteristics, before any mutations are observed in descendant viruses. By analyzing codon frequency and spatial distribution patterns in the ancestral genome, the system predicts which segments will be conserved, enabling therapeutic development for novel viruses without requiring prior mutation data from virus family members.
Data Source
AI summary
Provided are a system and method for estimating mutability of genomic segments from a reference genomic sequence. The method including: receiving the reference genomic sequence and coding regions for the genomic sequence; dividing the reference genomic sequence into genomic codons; determining an importance value for each genomic codon, the importance value representative of an estimation of the mutability of the genomic codon, the importance value including a combination of eccentricity of the genomic codon and frequency of occurrence of the genomic codon in a coding region of the genomic sequence; and outputting the importance value of each genomic codon as an estimation of the mutability of such genomic codon.