Antigen Pool Decoding for Accurate Lymphocyte Receptor Sequencing
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Solution Overview
Problem
Existing methods for determining lymphocyte receptor sequences that recognize specific antigens suffer from high false positive and false negative rates, and there is a need for improved assays to accurately identify lymphocyte receptor chain sequences that bind to specific antigens in pool-based detection formats.
Innovation Solution
A method involving sorting antigens into unique subsets, contacting biological samples with lymphocytes, separating target lymphocytes, sequencing their nucleic acids, and using decoding algorithms to detect specific lymphocyte receptor chain sequences, with error-correcting codes to enhance accuracy and sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If pool-based detection formats are used to determine lymphocyte receptor sequences, then productivity is improved by testing multiple antigens simultaneously, but measurement precision deteriorates due to high false positive and false negative rates
Solution Approach 1:
The patent divides the pool-based detection into multiple sub-pools or reaction mixtures, where each antigen is assigned to specific subsets. By segmenting the detection process and using decoding algorithms to interpret patterns across subsets, the method maintains high throughput while improving accuracy in identifying specific lymphocyte-antigen interactions
Solution Approach 2:
The patent employs decoding algorithms that analyze detection patterns across multiple reaction mixtures to provide feedback on the reliability of identified lymphocyte-antigen interactions. This computational feedback mechanism helps distinguish true positives from false positives and negatives, thereby improving measurement precision while maintaining pool-based productivity
2Measurement precision
If conventional single-antigen testing methods are used, then measurement precision is maintained with accurate identification, but productivity deteriorates due to sequential testing requirements
Solution Approach 1:
The patent merges multiple single-antigen tests into a single pool-based detection format where multiple antigens are tested simultaneously. By combining detection reactions and using computational decoding to resolve individual antigen-specific responses, the method achieves both high productivity and maintained measurement precision
3Reliability
If error-correcting codes are implemented in the detection algorithm, then reliability is improved by reducing false positives and negatives, but device complexity increases due to computational requirements
Solution Approach 1:
The patent introduces computational decoding algorithms as an intermediary between the pool-based detection data and the final identification of lymphocyte-antigen interactions. This computational mediator processes the complex pattern data from multiple reaction mixtures, applying error-correcting logic to reliably identify specific interactions while managing system complexity through software rather than hardware complexity
Data Source
AI summary
Described herein is a method for determining a lymphocyte cell receptor chain sequence specific to a unique antigen, comprising: sorting a plurality of antigens into a plurality of reaction mixtures, wherein the sorting comprises adding a unique antigen of the plurality of antigens to a unique subset of the plurality of reaction mixtures such that two different unique antigens are not added to the unique subset; contacting each reaction with a biological sample comprising a plurality of lymphocytes; separating a target lymphocyte from a subset of the plurality of lymphocytes, wherein the target lymphocyte recognizes the unique antigen; after separating the target lymphocyte, sequencing nucleic acids of the target lymphocyte to obtain the lymphocyte receptor chain sequence, wherein the sequencing is performed by single-cell sequencing; and detecting the unique antigen, wherein the detecting comprises: computing a frequency of lymphocyte cells that express the lymphocyte receptor chain sequence.