Genome Segment Count Representation Without Alignment
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Solution Overview
Problem
Current diagnostic tests for genetic variations, such as those causing medical conditions or predispositions, often rely on aligning sequence reads to a reference genome, which can be complex and inefficient, particularly in non-invasive prenatal diagnostics where rapid and accurate chromosome representation is crucial.
Innovation Solution
A computer-implemented method that generates a count representation of a genome segment by comparing nucleic acid sequence reads to a listing of polynucleotides without aligning them to a reference genome, using counts A and B to determine a ratio that indicates genetic variations, enabling diagnostic tests for conditions like chromosomal aneuploidy without the need for alignment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If sequence reads are aligned to a reference genome, then measurement precision of genetic variations is improved, but device complexity and processing time increase
Solution Approach 1:
The patent extracts and counts only the specific polynucleotides of interest from the sequence reads without performing full alignment to the reference genome. This selective extraction approach maintains detection accuracy for targeted genetic variations while eliminating the computational complexity of comprehensive alignment processes.
Solution Approach 2:
The reference genome is segmented into specific polynucleotide sequences of interest, and the method focuses on counting reads matching these segmented regions rather than aligning reads across the entire genome. This segmentation strategy reduces processing complexity while preserving measurement precision for the targeted segments.
2Reliability
If alignment process is performed, then reliability of chromosome representation is improved, but productivity and speed of diagnostic test decrease
Solution Approach 1:
The patent performs preliminary counting of sequence reads against a database of known polynucleotide sequences before conducting full alignment. This preliminary action provides a reliable chromosome representation quickly, enabling rapid diagnostic results while maintaining accuracy through subsequent verification steps.
Solution Approach 2:
The method skips the time-consuming alignment step by directly counting reads that match polynucleotide sequences in the database. This rushing through the diagnostic process maintains reliability by focusing on critical matching regions while significantly improving test speed and productivity.
3Measurement precision
If full genome alignment is performed, then completeness of genetic variation detection is improved, but loss of time and computational resources increase
Solution Approach 1:
The patent applies local quality by focusing computational resources on counting and analyzing specific polynucleotide sequences of clinical interest rather than uniformly processing the entire genome. This localized approach maintains detection completeness for critical regions while reducing overall processing time and resource consumption.
Data Source
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Figure 3A~3C
AI summary
The present invention relates to a method for determining a sequence read count representation of a genome segment for a diagnostic test, comprising: (a) generating a count of nucleic acid sequence reads for a genome segment, which sequence reads are reads of nucleic acid from a test sample from a subject having the genome, thereby providing a count A for the segment; (b) generating a count of nucleic acid sequence reads for the genome or a subset of the genome, thereby providing a count B for the genome or subset of the genome; and (c) determining a count representation for the segment as a ratio of the count A to the count B, wherein the sequence reads are not subjected to an alignment process that aligns the sequence reads to the reference genome in (a), (b) and (c).