Aneuploidy ITH Scoring From Single-Biopsy Tumor Samples
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Solution Overview
Problem
Current methods for determining aneuploidy-based intratumor heterogeneity (ITH) in cancer are inadequate, particularly for predicting therapy resistance and prognosis, as they often rely on unavailable or inefficient analysis techniques.
Innovation Solution
Methods and systems are developed to characterize significantly clonal and subclonal aneuploidy events using longitudinal biopsies, enabling the generation of a patient-specific aneuploidy-based ITH metric by comparing aneuploidy events in a single sample against reference data from multiple samples, integrating with other ITH metrics like structural variants and mRNA-based ITH.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods utilizing short variants are used to determine aneuploidy-based ITH, then the analysis can be performed with available techniques, but the predictive accuracy of aneuploidy-based ITH is insufficient
Solution Approach 1:
The patent replaces traditional short variant analysis methods with whole genome sequencing technology to detect aneuploidy events. This substitution enables comprehensive detection of chromosomal copy number variations across the entire genome, significantly improving the predictive accuracy of aneuploidy-based ITH measurements while providing a complete genomic view that short variants cannot achieve.
2Measurement precision
If multiple biopsies are performed to characterize aneuploidy events, then the accuracy of ITH determination is improved, but the complexity and invasiveness of the procedure increases
Solution Approach 1:
The patent segments the complex task of ITH determination into two distinct phases: (1) training phase using longitudinal biopsy data from multiple patients to build reference models of clonal vs. subclonal aneuploidy events, and (2) application phase using single biopsy data from individual patients to calculate ITH metrics. This segmentation allows accurate ITH determination from single biopsies by leveraging patterns learned from multiple biopsies during training.
Solution Approach 2:
The patent performs preliminary analysis by collecting and analyzing longitudinal biopsy data from multiple patients beforehand to establish reference models. These pre-built models contain knowledge about which aneuploidy events are typically clonal versus subclonal in different cancer types, enabling accurate ITH assessment from single future biopsies without repeating the complex longitudinal sampling process.
3Ease of operation
If single sample analysis is used to generate ITH metrics, then the ease of operation is improved, but the reliability of aneuploidy-based ITH determination deteriorates
Solution Approach 1:
The patent introduces computational models and algorithms as intermediaries between single biopsy data and ITH determination. These models process the single sample's aneuploidy events by comparing them against reference patterns from longitudinal studies, effectively mediating the translation of single-sample data into reliable ITH metrics that account for tumor evolution and heterogeneity.
Solution Approach 2:
The patent creates virtual representations of tumor evolution by copying and analyzing patterns from longitudinal biopsy data. The computational models replicate the temporal dynamics of aneuploidy acquisition observed in multi-timepoint studies, allowing single biopsy samples to be evaluated against these copied evolutionary patterns to reliably estimate ITH without actual longitudinal sampling.
Data Source
AI summary
Methods for characterizing aneuploidy based intratumor heterogeneity for a tumor of a tumor type for a subject. The methods may comprise, for example, obtaining sample aneuploidy data for the tumor, calling subclonal aneuploidy events in the sample aneuploidy data and generating an intratumor heterogeneity score for the tumor sample, and use of the aneuploidy based intratumor heterogeneity in cancer treatment and prognostics.