Mitochondrial DNA Structural Variant Detection in Circular Genomes

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Solution Overview

Problem

Existing variant callers designed for linear chromosomal DNA fail to accurately identify structural variants in mitochondrial DNA due to its circular structure and higher mutation frequency, leading to improper alignments and missed detections.

Innovation Solution

A system and method that includes preprocessing, mapping, filtering, and analyzing mitochondrial sequencing data to identify structural variants such as deletions, insertions, duplications, and inversions by using a sequencing system with a data parser, mapping engine, filtering engine, and analytics engine to process and align query sequences with mitochondrial DNA.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard variant callers designed for linear chromosomal DNA are used, then the analysis process is simple, but they fail to accurately identify structural variants in mitochondrial DNA due to its circular structure and higher mutation rates

Engineering Contradiction:

Improveaccuracy of structural variant identificationVSAvoidcomplexity of alignment and filtering process

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the parameters of the alignment process by implementing specialized alignment algorithms that account for the circular structure of mitochondrial DNA, adjusting scoring thresholds, and modifying filtering criteria to accommodate higher mutation rates. This allows accurate identification of structural variants while managing the increased complexity through parameter optimization.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If specialized alignment and filtering processes are implemented for mitochondrial DNA, then structural variants can be accurately identified, but the computational complexity and processing time increase

Engineering Contradiction:

Improveaccuracy of structural variant detectionVSAvoidprocessing time for sequencing data analysis

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary filtering and preprocessing steps to mitochondrial sequencing data before full analysis. By pre-identifying potential structural variants using simplified criteria and then applying more rigorous validation only to candidate regions, the system achieves high accuracy while reducing overall processing time and computational resource requirements.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If standard variant calling methods are used, then the workflow is straightforward, but deletions, insertions, duplications, and inversions in mitochondrial DNA are missed or misidentified

Engineering Contradiction:

Improvereliability of variant identificationVSAvoidcomplexity of specialized variant calling system

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the variant calling process into distinct modules: initial alignment with circular DNA awareness, structural variant-specific detection algorithms for different variant types (deletions, insertions, duplications, inversions), and hierarchical filtering stages. This segmentation improves reliability by addressing each variant type with specialized methods while managing system complexity through modular design.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS12614609B2Systems and methods to identify mutations in mitochondrial genomes

Publication Date: 2026.04.28 QUEST DIAGNOSTICS INVESTMENTS INC

AI summary

The present disclosure describes a sequencing system configured to identify structural variants in mitochondrial DNA. Variant callers configured to identify variants in linear genomes (e.g., those found in chromosomes) can fail to properly identify structural variants in mitochondrial DNA. The system and methods can identify structural variants in next generation sequencing data collected from circular, mitochondrial DNA.