Multiplex Genetic Analysis Using Overlapping Probes and Identifier Tracking
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Solution Overview
Problem
Current genetic analysis technologies face challenges in accurately and cost-effectively determining allelic status for multiple genetic loci in large numbers of patients due to high frequencies of incorrect or ambiguous calls, which are not readily resolved without additional expensive assays or steps.
Innovation Solution
The use of overlapping probes labeled with different identifiers to track assay reactions, combined with techniques like molecular inversion probes and differentiator tag sequences, to address systematic and stochastic errors in genetic analysis, allowing for more confident genetic calls and improved allelic representation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current genetic analysis technologies are used to determine allelic status for multiple genetic loci in large numbers of patients, then analysis throughput is achieved, but error frequency and ambiguity increase
Solution Approach 1:
The patent divides the genetic analysis process into multiple independent assay reactions, each targeting specific genetic loci with dedicated probes. By segmenting the analysis into discrete, trackable reactions rather than bulk processing, the system maintains reliability while achieving throughput through parallelization of multiple segmented assays.
Solution Approach 2:
The patent implements feedback mechanisms through identifier tracking that monitors and records the outcome of each assay reaction. This feedback system allows real-time detection of errors and ambiguities, enabling corrective actions or re-analysis of specific reactions without affecting the entire batch, thus maintaining high reliability at scale.
2Reliability
If additional expensive assays or steps are used to resolve uncertainties, then reliability improves, but cost and time increase
Solution Approach 1:
The patent applies preliminary action by incorporating unique identifiers and tracking mechanisms at the outset of the assay process, before uncertainties arise. This preemptive labeling allows direct tracking and resolution of specific reactions needing verification, eliminating the need for time-consuming blanket re-analysis and reducing both time and cost while maintaining reliability.
Solution Approach 2:
The patent uses identifier sequences as informational copies that track the fate and results of each assay reaction throughout the process. These molecular copies provide a record that enables rapid identification and resolution of uncertain results without requiring physical re-performance of entire assays, thus reducing time and cost while improving confidence in results.
3Measurement precision
If overlapping probes with different identifiers are used to track assay reactions, then measurement precision improves, but device complexity increases
Solution Approach 1:
The patent applies universality by designing probes that simultaneously perform multiple functions: they hybridize to target sequences for specific detection, incorporate unique identifiers for tracking, and enable both qualitative and quantitative analysis. This multi-functionality allows precise allelic representation measurement without proportionally increasing system complexity, as the same probe structure serves multiple purposes.
Solution Approach 2:
The patent utilizes parameter changes by varying the identifier sequences within probes while maintaining consistent target-binding regions. This allows the system to distinguish between different assay reactions and track their outcomes with high precision, while the standardized binding regions keep the overall system complexity manageable through modular design.
Data Source
AI summary
Aspects of the invention relates to methods and compositions that are useful to reduce bias and increase the reproducibility of multiplex analysis of genetic loci. In some configurations, predetermined preparative steps and/or nucleic acid sequence analysis techniques are used in multiplex analyses for a plurality of genetic loci in a plurality of samples.