Viral Chimeric Reference Sequences for Tumor Integration and Co-Amplification
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Solution Overview
Problem
Current treatments for HPV-associated cervical cancer are ineffective for infected patients, and there is a lack of understanding in molecular events between the pathogen's and patient's genomes to tailor therapies effectively.
Innovation Solution
A method involving a chimeric reference nucleic acid sequence that combines viral and mammalian nucleic acid sequences to identify integration and co-amplification events, allowing for the identification of oncogenes like ERBB2, which informs targeted treatment recommendations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard chemoradiation treatment is used for HPV-associated cervical cancer, then treatment is provided to patients, but treatment effectiveness is low with 15-45% of patients not cured
Solution Approach 1:
The patent performs preliminary genomic analysis of the tumor to identify viral integration sites and co-amplified oncogenes before treatment selection. This preliminary characterization of the tumor's molecular profile enables subsequent personalized treatment decisions, moving from empirical treatment to targeted therapy based on pre-identified molecular targets.
Solution Approach 2:
The patent uses feedback from genomic sequencing data to guide treatment selection. The treatment recommendation system incorporates feedback about specific viral integrations and co-amplified genes to select targeted therapies, creating a closed-loop system where treatment is continuously optimized based on molecular profile data.
2Adaptability or versatility
If genomic analysis methods are developed to understand molecular events between pathogen and patient genomes, then personalized treatment strategies can be identified, but current methods lack the capability to detect viral integration and co-amplification events
Solution Approach 1:
The patent introduces an intermediary computational analysis system that bridges raw sequencing data and clinical interpretation. This intermediary layer includes algorithms specifically designed to detect viral integration sites and co-amplification events, translating complex genomic data into actionable clinical insights about oncogene amplification and viral-host interactions.
Solution Approach 2:
The patent changes the detection parameters by focusing specifically on regions of the genome where viral integration is most likely to occur and where oncogene amplification is most clinically relevant. The method prioritizes detection of specific genomic alterations (viral integrations, co-amplifications) rather than attempting to analyze the entire genome uniformly, improving detection precision for clinically actionable events.
Data Source
AI summary
Contemplated systems and methods employ chimeric reference sequences that include a plurality of viral genome sequences to identify/quantify integration and co-amplification events. Most typically, the viral genome sequences are organized in the chimeric reference sequences as single chromosomes and the chimeric reference sequences are in BAM format.