LPA Copy Number Analysis Using Short-Read Sequencing for Lp(a) Diagnosis
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Solution Overview
Problem
Current methods for determining Lp(a) levels, which are associated with cardiovascular conditions, are expensive, difficult to perform, and require specialized equipment, leading to underdiagnosis of related cardiac conditions.
Innovation Solution
A method using short-read sequencing technology to generate pseudocounts of copy number variants (CNVs) in the LPA gene by masking specific regions, allowing for accurate and cost-effective determination of Lp(a) levels, facilitating patient selection for interventions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If long-read sequencing equipment or gel electrophoresis is used to determine CNVs in LPA, then measurement capability is achieved, but cost and equipment complexity increase significantly
Solution Approach 1:
The patent uses short-read sequencing data (copies of genomic regions) to infer Lp(a) levels through pseudocount analysis, rather than directly measuring Lp(a) or using long-read sequencing. This copying approach allows determination of CNVs using readily available short-read data from standard genomic sequencing, eliminating the need for specialized long-read equipment while maintaining measurement capability through computational inference
Solution Approach 2:
The patent employs standard short-read sequencing technology (inexpensive and widely available) instead of costly long-read sequencing equipment or gel electrophoresis. The short-read data, while individually less informative, can be aggregated through pseudocount analysis to achieve the desired measurement precision at a fraction of the cost and complexity
2Measurement precision
If long-read sequencing or gel electrophoresis is performed, then Lp(a) level assessment is possible, but procedural difficulty and specialization requirements increase
Solution Approach 1:
The method uses copies of genomic information already obtained through standard short-read sequencing to infer Lp(a) levels, avoiding the need for specialized testing procedures. The pseudocount analysis computes Lp(a) assessment from existing short-read data copies, making the procedure accessible to standard genomics laboratories without specialized equipment or expertise
Solution Approach 2:
The patent enables Lp(a) level assessment to be performed as a byproduct of standard genomic sequencing workflows. The pseudocount analysis automatically processes short-read data to determine CNVs and infer Lp(a) levels without requiring separate specialized testing procedures, making the assessment self-serviceable within existing genomic analysis pipelines
3Measurement precision
If specialized equipment and procedures are used for Lp(a) testing, then diagnostic accuracy is achieved, but accessibility and adoption rate decrease
Solution Approach 1:
The patent makes Lp(a) level determination a universal application of standard short-read sequencing. By using pseudocount analysis on routinely generated short-read data, the method enables Lp(a) assessment across all genomic sequencing projects without requiring specialized equipment or separate testing workflows, dramatically increasing accessibility and diagnostic rate while maintaining measurement precision
Solution Approach 2:
The patent merges Lp(a) level determination with standard genomic sequencing workflows. The pseudocount analysis integrates CNV inference from short-read data into existing sequencing pipelines, combining multiple functions (genomic analysis and Lp(a) assessment) into a single unified process, thereby increasing productivity and diagnostic rate without sacrificing accuracy
Data Source
AI summary
Systems and methods are provided for selecting a patient for intervention relating to genetically predicted lipoprotein (a) (“Lp(a)”) levels. A method may obtain or having obtained a biological sample from the patient. A method may perform or having performed sequencing on the biological sample, comprising. A method may acquire reads for the patient. A method may mask at least one portion of a gene LPA at a reference genome to facilitate alignment of the reads to a reference genome. A method may determine a pseudocount of copy number within the gene LPA at a genome of the patient. A method may in an event that the pseudocount is not an expected amount, selecting the patient for the intervention. A method may in an event that the pseudocount is an expected amount, omitting selection of the patient for the intervention.