Size-Selected cfDNA Sequencing for Cancer Classification
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Solution Overview
Problem
Current methods for classifying cancer using cell-free DNA sequencing are slow, expensive, and limited in diagnostic power, especially for early-stage and low-tumor fraction cancers, due to the need for whole genome or exome sequencing and low specificity of existing biomarkers.
Innovation Solution
The use of size-selected cell-free DNA sequencing reads, where size selection occurs in vitro or in silico, enriches the fraction of cancer-derived DNA fragments, allowing for more sensitive and cost-effective classification of cancers, including those with low tumor fractions, by focusing on fragments shorter than 160 nucleotides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If whole genome or exome sequencing is used for cancer classification, then comprehensive genetic information is obtained, but the process becomes slow and expensive
Solution Approach 1:
The patent extracts only the relevant portion of DNA (fragments shorter than 160 nucleotides) that are most likely to be cancer-derived, rather than sequencing the entire genome. This selective extraction maintains diagnostic power while dramatically reducing sequencing time and cost.
Solution Approach 2:
The patent changes the size parameter of DNA fragments being analyzed, focusing specifically on fragments shorter than 160 nucleotides. This parameter change enriches for cancer-derived DNA and enables faster, more cost-effective sequencing while maintaining or improving diagnostic accuracy.
2Measurement precision
If whole genome or exome sequencing is used for cancer classification, then comprehensive genetic information is obtained, but sequencing costs increase
Solution Approach 1:
The patent extracts only the relevant portion of DNA (fragments shorter than 160 nucleotides) that are most likely to be cancer-derived, rather than sequencing the entire genome. This selective extraction maintains diagnostic power while dramatically reducing sequencing time and cost.
Solution Approach 2:
The patent performs partial sequencing by focusing only on short DNA fragments (<160 nt) rather than complete genome sequencing. This partial action is sufficient to achieve the diagnostic objective while reducing costs.
3Ease of operation
If existing biomarkers are used for cancer detection, then noninvasive screening is enabled, but specificity is low resulting in high false-positive rates
Solution Approach 1:
The patent changes the size parameter of DNA fragments being analyzed, focusing specifically on fragments shorter than 160 nucleotides. This parameter change enriches for cancer-derived DNA and enables faster, more cost-effective sequencing while maintaining or improving diagnostic accuracy.
4Measurement precision
If size selection is performed in vitro, then cancer-derived DNA fragments are enriched, but additional processing steps are required
Solution Approach 1:
The patent replaces the mechanical in vitro size selection process with computational in silico filtering. Sequence reads are filtered based on length criteria after sequencing, eliminating the need for additional wet lab processing steps while achieving the same enrichment goal.
Data Source
AI summary
Systems and methods for determining a cancer class of a subject are provided in which a plurality of sequence reads, in electronic form, are obtained from a biological sample of the subject. The sample comprises a plurality of cell-free DNA molecules including respective DNA molecules longer than a threshold length of less than 160 nucleotides. The plurality of sequence reads excludes sequence reads of cell-free DNA molecules in the plurality of cell-free DNA molecules longer than the threshold length. The plurality of sequence reads is used to identify a relative copy number at each respective genomic location in a plurality of genomic locations in the genome of the subject. The genetic information about the subject obtained from the sample and the genetic information consisting of the identification of the relative copy number at each respective genomic location, is applied to a classifier that determines the cancer class of the subject.