cfDNA End-Sequence Analysis for Sensitive Cancer Detection

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Solution Overview

Problem

Current cfDNA-based cancer detection methods lack sufficient sensitivity while maintaining high specificity, necessitating improved techniques for earlier cancer detection.

Innovation Solution

Analyze the end sequences and GC content of cfDNA fragments to identify a relationship indicative of cancer, utilizing methods that determine the end sequence and GC content of cfDNA fragments to differentiate between cancerous and non-cancerous samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cfDNA-based cancer detection methods are used, then cancer detection capability is improved, but sensitivity is insufficient while maintaining high specificity

Engineering Contradiction:

Improvecancer detection capabilityVSAvoidsensitivity

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent segments the analysis of cfDNA by focusing on specific fragment characteristics (end sequences and GC content) rather than analyzing all cfDNA properties uniformly. This segmentation allows for more precise detection of cancer-specific patterns while maintaining high specificity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by examining specific local features of cfDNA fragments (the end sequences and GC content at fragment ends) rather than treating all cfDNA equally. This localized analysis improves sensitivity by focusing on the most informative regions that distinguish cancerous from non-cancerous samples.

Inventive Principle:

Principle #3Local quality

2Loss of time

If earlier cancer detection is pursued, then detection time is improved, but detection accuracy may be compromised due to lower tumor burden

Engineering Contradiction:

Improvedetection timeVSAvoiddetection accuracy

Core Design Contradiction:

Loss of timeVSMeasurement precision

Solution Approach 1:

The patent changes the analytical parameters from traditional genetic alterations to epigenetic markers (end sequences and GC content patterns). These parameter changes enable detection of cancer-specific signatures even when tumor burden is low, thus maintaining detection accuracy while enabling earlier detection.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent substitutes traditional genetic analysis methods with epigenetic analysis of cfDNA fragmentation patterns. This substitution allows for detection of cancer signals that are present even at early stages with low tumor burden, thereby maintaining accuracy while enabling earlier detection.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20250327131A1Methods for identifying cancer in a subject

Publication Date: 2025.10.23 JOHNS HOPKINS UNIVERSITY

AI summary

Provided herein are methods of identifying a subject as having a disease, the method comprising: (a) obtaining a biological sample from the subject, wherein the biological sample comprises cell-free DNA (cfDNA), wherein the cfDNA comprises a plurality of cfDNA fragments; (b) determining an end sequence of a cfDNA fragment of the plurality of cfDNA fragments; (c) determining a level of GC content of the cfDNA fragment; and (d) analyzing the determined end sequence and the level of GC content of the cfDNA fragment, thereby identifying the subject as having the disease by determining a relationship between the determined end sequence and the level of GC content of the cfDNA fragment.