Genomic Data Compression Using Modified Reference Genomes

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Solution Overview

Problem

The challenge in compressing genomic data, particularly from bisulfite sequencing, is the high number of mismatches between read sequences and reference genomes due to bisulfite treatment, which reduces compression ratios and increases storage costs.

Innovation Solution

The approach involves using a set of modified reference genomes that account for methylation changes, such as converting C to T and G to A, to reduce mismatches and improve compression ratios during genomic data mapping and storage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If a standard reference genome is used for compression, then the compression process is simple, but the compression ratio is poor due to high number of mismatches from bisulfite treatment

Engineering Contradiction:

Improvecompression process complexityVSAvoidcompression ratio

Core Design Contradiction:

Device complexityVSLoss of information

Solution Approach 1:

The reference genome is segmented into multiple versions (standard reference and bisulfite-treated reference) to handle different sequencing conditions. This allows the compression system to select the appropriate reference version based on whether the read data comes from bisulfite-treated or untreated samples, thereby reducing mismatches and improving compression ratio without increasing overall system complexity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The reference genome sequence parameters are changed by applying bisulfite conversion rules (C→T and G→A substitutions) to create a specialized reference version for methylated DNA sequencing. This parameter transformation aligns the reference with the modified read data, significantly reducing the number of mismatches and improving compression efficiency

Inventive Principle:

Principle #35Parameter changes

2Loss of information

If multiple modified reference genomes are used to reduce mismatches, then the compression ratio improves, but the device complexity increases

Engineering Contradiction:

Improvecompression ratioVSAvoidreference genome management complexity

Core Design Contradiction:

Loss of informationVSDevice complexity

Solution Approach 1:

The bisulfite-treated reference genome is pre-generated and stored before actual compression operations. This preliminary preparation allows the compression system to directly use the pre-converted reference without performing complex real-time transformations, thereby improving compression ratio while keeping the operational complexity manageable

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

Instead of creating entirely new reference genomes from scratch, the system copies and modifies the standard reference genome by applying systematic nucleotide substitutions (C→T, G→A) to create a derived reference version. This copying approach maintains structural similarity while adapting to specific sequencing conditions, balancing compression improvement with complexity control

Inventive Principle:

Principle #26Copying

3Measurement precision

If bisulfite treatment is applied to detect methylation, then methylation analysis accuracy improves, but the number of mismatches with reference genome increases

Engineering Contradiction:

Improvemethylation detection accuracyVSAvoidcompression ratio

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The harmful effect of bisulfite-induced mismatches is converted into a benefit by using the same conversion rules to transform the reference genome. The mismatches caused by bisulfite treatment are systematically addressed by applying identical C→T and G→A substitutions to the reference, thereby converting the source of compression problems into a solution that improves both methylation detection accuracy and compression efficiency

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This method enhances compression ratios by a factor of 2 or more, reducing storage requirements and costs, while maintaining accurate data representation for analysis in disease detection and diagnostics.

Implementation Method 1

Bisulfite sequencing is a method for detecting epigenetic methylation patterns at single-base resolution. This technique involves chemically treating DNA with sodium bisulfite, which converts unmethylated cytosine bases to uracil, but does not alter methylated cytosines.

Methodology Applied

Scientific EffectBisulfite conversion:

Implementation Method 2

The present disclosure improves mapping technology by comparing an obtained data read to each of a plurality of different reference genomes. The plurality of reference genomes can include an unchanged reference genome, a reference genome that has been modified to convert C to T, and a reference genome that has been modified to convert G to A.

Methodology Applied

Scientific EffectReference-based compression:

Data Source

PatentUS20250046399A1Compression techniques for genomic data

Publication Date: 2025.02.06 ILLUMINA INC

AI summary

Methods, systems, and apparatus, including computer programs encoded on computer-storage media, for compressing genomic data. One of the methods includes obtaining a genomic data read; mapping the read to a plurality of different candidate reference genomes; selecting one of the candidate reference genomes based on the mapping; performing reference-based compression of the read using the selected reference genome; and storing the compressed genomic data read.