Targeted Sequencing Read Mapping via Alternate Region Segmentation

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Solution Overview

Problem

Current targeted sequencing methods are computationally expensive due to the need to align sequencing reads to the entire genome, which can lead to errors and inefficiencies, especially when analyzing specific regions of interest, as they often include false positive reads from non-target regions.

Innovation Solution

The method identifies alternate regions similar to the target region, allowing sequencing reads to be aligned only to the target region and its corresponding alternate regions, thereby reducing computational effort and excluding false positives by comparing reads to both the target and alternate regions, and using a mutation count filter to discard significantly different reads.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sequencing reads are aligned to the entire genome to ensure accuracy, then measurement precision is improved, but computational complexity and processing time increase significantly

Engineering Contradiction:
Improveaccuracy of mutation detectionVSAvoidcomputational processing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the genome into target regions and alternate regions, separating the alignment process from the entire genome to only these specific segments. This segmentation maintains measurement precision by including both target and alternate regions while reducing computational time by excluding the rest of the genome.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary identification of alternate regions before the alignment process. By pre-identifying regions that are similar to target regions, the system prepares the necessary data structures and region definitions in advance, allowing the alignment step to focus only on relevant regions without performing genome-wide scanning.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If sequencing reads are aligned to the entire genome, then reliability of read assignment is improved, but device complexity and computational resources increase

Engineering Contradiction:
Improveaccuracy of read mappingVSAvoidcomputational system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The genome is segmented into target regions and pre-identified alternate regions. This segmentation reduces device complexity by limiting the alignment search space from the entire genome to only these specific segments, while maintaining reliability through the inclusion of alternate regions that could contain reads originating from similar sequences.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Alternate regions are preliminarily identified and stored before the alignment process. This preliminary action simplifies the alignment device complexity by pre-computing and storing region definitions, allowing the alignment step to simply compare reads against these predefined regions rather than performing de novo genome-wide alignment.

Inventive Principle:
Principle #10Preliminary action

3Productivity

If all sequencing reads are processed through complete genome alignment, then productivity is maintained, but loss of energy and computational resources increases

Engineering Contradiction:
Improvethroughput of variant detectionVSAvoidcomputational energy consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The alignment process is segmented to focus only on target and alternate regions rather than the entire genome. This segmentation maintains productivity by quickly processing reads through a reduced search space while significantly reducing computational energy consumption by avoiding unnecessary comparisons with the rest of the genome.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Alternate regions are preliminarily identified and stored, enabling efficient energy-use during the alignment phase. The preliminary identification allows the system to avoid repeated genome-wide searches, maintaining high throughput while reducing energy consumption by performing the expensive identification step only once.

Inventive Principle:
Principle #10Preliminary action

4Productivity

If reads are aligned only to target regions without considering alternate regions, then computational efficiency is improved, but measurement precision deteriorates due to false positives

Engineering Contradiction:
Improvecomputational efficiencyVSAvoidaccuracy of variant calling
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the genome into target regions and alternate regions, allowing efficient alignment to these specific segments rather than the entire genome. This segmentation maintains computational efficiency while improving measurement precision by explicitly including alternate regions in the alignment process, enabling the system to distinguish true target reads from reads originating from similar sequences.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP2926288B1Accurate and fast mapping of targeted sequencing reads
Publication Date: 2021.03.17 ROCHE DIAGNOSTICS GMBH
  • EP2926288B1 patent drawingFigure 1
  • EP2926288B1 patent drawingFigure 2A~2B
  • EP2926288B1 patent drawingFigure 3

AI summary

Accurate and fast mapping of sequencing reads obtained from a targeted sequencing procedure can be provided. Once a target region is selected, alternate regions of the genome that are sufficiently similar to the target region can be identified. If a sequencing read is more similar to the target region than to an alternate region, then the read can be determined as aligning to the target region. The reads aligning to the target region can then be analyzed to determine whether a mutation exists in the target region. Accordingly, a sequencing read can be compared to the target region and the corresponding alternate regions, and not to the entire genome, thereby providing computational efficiency.