Ultra-low coverage genome sequencing for rare variant identification

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Solution Overview

Problem

Current sequencing-based genotyping techniques are cumbersome, time-consuming, and lack the reliability and accuracy needed for commercial viability, particularly in identifying rare disease variants and elucidating cryptic relatedness among genetic samples, while low-coverage sequencing methods suffer from high error rates and are not economically viable.

Innovation Solution

A method utilizing ultra-low coverage sequencing with advanced data processing and reference genome alignment to infer genetic and phenotypic information, including ancestry and relatedness, without the need for genotype imputation, using a database to store and analyze aligned reads, enabling accurate identification of rare variants and cryptic relationships.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high coverage sequencing (30x) is used to ensure accurate genotype identification, then reliability and accuracy are improved, but cost and time requirements increase significantly making it commercially unviable

Engineering Contradiction:

Improvegenotype identification accuracyVSAvoidcost and time efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies partial action by using ultra-low coverage sequencing (0.001x to 1x) instead of full high-coverage sequencing, obtaining only the minimum necessary genetic information needed to identify rare variants and cryptic relationships while significantly reducing cost and time requirements

Inventive Principle:

Principle #16Partial or excessive action

2Productivity

If low coverage sequencing (1x to 10x) is used to reduce cost and time, then productivity is improved, but error rates increase and reliability decreases

Engineering Contradiction:

Improvecost and time efficiencyVSAvoidgenotype identification accuracy

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies local quality by focusing sequencing efforts on specific genomic regions that are most informative for identifying rare variants and cryptic relationships, rather than attempting to achieve uniform coverage across the entire genome, thereby maintaining reliability in critical areas while reducing overall cost and time

Inventive Principle:

Principle #3Local quality

3Productivity

If ultra-low coverage sequencing (about 1x or less) is used to minimize cost and time, then productivity is significantly improved, but measurement precision and reliability deteriorate due to high error rates

Engineering Contradiction:

Improvecost and time efficiencyVSAvoidgenetic variant identification accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies the intermediary principle by using statistical models and computational algorithms as mediators between the ultra-low coverage sequencing data and the final genotype calls, allowing accurate identification of rare variants and cryptic relationships despite the limited and noisy input data

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP3497241B1Ultra-low coverage genome sequencing and uses thereof

Publication Date: 2024.01.10 NEW YORK GENOME CENT

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AI summary

Methods are provided for analyzing one or more genetic samples, comprising procuring one or more genetic samples comprising genetic material from one or more individuals and sequencing the genetic material using non-targeted, ultra-low coverage sequencing to obtain genetic information for individual associated with the one or more genetic samples. Personal and genetic information associated with the individuals is stored in a database for retrieval and manipulation.