Urine Sediment DNA Classification for Urogenital Tumor Detection

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Solution Overview

Problem

Current methods for diagnosing urogenital tumors, such as renal cancer, bladder cancer, and prostate cancer, face challenges with low sensitivity and specificity, particularly in early detection and non-invasive monitoring, due to the low level of signal in urine-based liquid biopsies and the heterogeneity of tumors, leading to missed diagnoses at advanced stages.

Innovation Solution

A method involving the detection of copy number variations (CNVs) and methylation haplotype load (MHL) in urine sediment genomic DNA, using DNA classification techniques like random forest models to differentiate tumor patients from healthy individuals and localize urogenital tumors, with the integration of clinical prognostic data to construct specific markers for bladder and renal cancer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If urine-based liquid biopsy is used for non-invasive diagnosis of urogenital tumors, then patient trauma is reduced, but diagnostic sensitivity and specificity are low due to low signal level

Engineering Contradiction:

Improvepatient traumaVSAvoiddiagnostic sensitivity and specificity

Core Design Contradiction:

Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent transforms the detection parameters from simple presence/absence of tumor markers to comprehensive analysis of copy number variations (CNVs) and methylation haplotype loads (MHL) across multiple genomic regions. This parameter transformation enables detection of low-level tumor signals in urine that were previously undetectable, achieving both non-invasiveness and high diagnostic accuracy

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent combines multiple detection dimensions (CNV data, MHL data, and their integration) to create a composite diagnostic approach. By integrating these different types of genomic information, the method achieves superior diagnostic performance compared to single-marker approaches, resolving the contradiction between non-invasive sampling and diagnostic precision

Inventive Principle:

Principle #40Composite materials

2Measurement precision

If targeted deep sequencing is used to detect mutations in small number of tumor cfDNAs, then detection sensitivity may improve, but sequencing errors increase and cost rises

Engineering Contradiction:

Improvemutation detection sensitivityVSAvoidsequencing accuracy

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and focuses on specific genomic features (CNVs and methylation patterns) that are characteristic of tumor DNA, rather than attempting to detect all possible mutations. By extracting these key features, the method achieves reliable detection without requiring excessive sequencing depth, thereby maintaining both sensitivity and accuracy while reducing error rates

Inventive Principle:

Principle #2Taking out (Extraction)

3Measurement precision

If tissue biopsy is used as gold standard for diagnosis, then diagnostic accuracy is high, but patient trauma and invasiveness increase

Engineering Contradiction:

Improvediagnostic accuracyVSAvoidpatient trauma

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses urine sediment DNA as an intermediary that carries tumor genetic information from the primary tumor site. This intermediary allows indirect detection of tumor characteristics without direct tissue sampling, achieving high diagnostic accuracy while eliminating the trauma associated with invasive biopsies

Inventive Principle:

Principle #24Intermediary (Mediator)

4Adaptability or versatility

If cystoscopy with pathological examination is used for bladder tumor diagnosis, then comprehensive examination is achieved, but diagnostic sensitivity remains low and patient discomfort increases

Engineering Contradiction:

Improveexamination comprehensivenessVSAvoiddiagnostic sensitivity

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent shifts the diagnostic dimension from direct visual and pathological examination of the bladder (spatial dimension) to molecular genetic analysis of urine DNA (genomic dimension). This dimensional shift allows detection of tumor genetic signatures that are not visible through conventional endoscopic methods, achieving higher sensitivity while maintaining comprehensive assessment capability

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

Data Source

PatentUS20230126920A1Method and device for classification of urine sediment genomic DNA, and use of urine sediment genomic DNA

Publication Date: 2023.04.27 BEIJING INSTITUTE OF GENOMICS CHINESE ACADEMY OF SCIENCES (CHINA NATIONAL CENTER FOR BIOINFORMATION)

AI summary

The present invention relates to a DNA classification method, comprising calculating the MHL value of a DNA methylation haplotype block and/or the DNA copy number variation data of a sample of interest; calculating the similarity between the MHL value of the DNA methylation haplotype block of the sample of interest DNA and the MHL value of a DNA methylation haplotype region of a respective classification label, and/or the similarity between the copy number variation data of the sample of interest DNA and the DNA copy number variation data of a respective classification label; and determining a classification for the DNA in the sample of interest by using a classifier model and based on the similarity. The present invention provides new means with good specificity and sensitivity for detection of tumors in the urogenital system.