Dynamic Genome Reference for NGS Variant Detection
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Solution Overview
Problem
Current DNA sequencing technologies face a bottleneck due to exponentially increasing data volumes, and the static human reference genome fails to represent human diversity adequately, introducing biases in variant detection.
Innovation Solution
A dynamic genome reference is generated using an automatically updated database of genetic variants, which is processed by a Next Generation Sequencing (NGS) bioinformatics ASIC to improve alignment accuracy and reduce computational time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a static reference genome is used for alignment, then the analysis process is simple and fast, but the reference does not adequately represent human diversity and introduces biases in variant detection
Solution Approach 1:
The patent transforms the static reference genome into a dynamic reference by incorporating population-level genetic variants. The system automatically updates the reference genome with variants from databases like dbSNP, creating a multi-allelic reference that adapts to represent diverse human populations while maintaining alignment accuracy.
2Productivity
If increasing numbers of CPU cores are used to process sequencing data, then data analysis speed improves, but the solution is not sustainable as data production outpaces Moore's Law
Solution Approach 1:
The patent changes the computational parameters by implementing a dynamic reference genome system that pre-processes and integrates population variants. This approach optimizes the alignment algorithm's efficiency, reducing computational time from hours to minutes without requiring proportional increases in CPU resources.
3Measurement precision
If a complete and diverse reference genome is constructed, then variant detection accuracy improves, but the complexity of the reference construction process increases
Solution Approach 1:
The patent applies preliminary action by pre-integrating population-level genetic variants into the reference genome before the actual sequencing analysis. The system automatically curates and incorporates variants from established databases, creating a comprehensive multi-allelic reference that simplifies subsequent variant detection while maintaining high accuracy.
4Adaptability or versatility
If all genetic variants are incorporated into the reference genome, then the representation of human diversity improves, but the size and complexity of the reference data increases
Solution Approach 1:
The patent applies local quality by incorporating genetic variants specifically at positions where population diversity exists, rather than uniformly expanding the entire reference genome. The system adds multi-allelic information only where needed to represent human diversity, maintaining a compact reference structure while improving adaptability to different populations.
Data Source
AI summary
A “dynamic” reference is presented that utilizes population level information to improve reference-based alignment to detect novel, deleterious, or functional variants in clinical sequencing applications. An automatically updated database of known genetic variants is provided to a memory connected with an integrated circuit configured for genetic sequence data with the dynamic reference and reference variants.