Single-Cell Receptor Clonotype Visualization for Antigen Specificity

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Solution Overview

Problem

Existing technologies face challenges in high-throughput characterization of immune cell responses and antigen specificity of antigen binding molecules, particularly in identifying and visualizing T cell and B cell receptor sequences, which are crucial for disease prevention and treatment, due to limitations in current assays like flow cytometry and bulk DNA/RNA sequencing.

Innovation Solution

A computer-implemented method and system for visualizing and analyzing immune cell clonotype data using single- and multi-modal single cell nucleic acid sequencing technologies, enabling dynamic display and interaction with visualization tools to assess antigen binding specificity and clonotype information.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If flow cytometry and bulk DNA/RNA sequencing are used to analyze immune cell responses, then the assays are simple and cost-effective, but the number of analytes that can be measured simultaneously is limited and high-throughput characterization is not achieved

Engineering Contradiction:
Improvehigh-throughput characterizationVSAvoidassay complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent combines multiple single-cell technologies (flow cytometry, CyTOF, single-cell RNA sequencing, single-cell DNA sequencing) into a unified multi-modal single-cell platform. This integration allows simultaneous measurement of numerous analytes including protein expression, gene expression, and genomic data from individual cells, achieving high-throughput characterization that overcomes the limitations of individual assays while maintaining systematic organization through integrated data analysis.

Inventive Principle:
Principle #5Merging (Combining)

2Quantity of substance

If multi-modal single cell technologies are used to measure multiple analytes simultaneously, then high-throughput characterization is achieved, but the complexity of the system and data analysis increases

Engineering Contradiction:
Improvenumber of analytesVSAvoidsystem complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent implements a universal single-cell analysis platform capable of measuring multiple analytes simultaneously including protein expression, gene expression, and genomic features. The system uses standardized single-cell barcoding and multi-omic sequencing approaches that can accommodate various analytes within a unified framework, enabling high-throughput characterization of immune cell responses while managing complexity through standardized protocols and integrated data structures.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If single cell assays are used to identify antigen-specific populations, then comprehensive clonotype analysis is achieved, but the time and resources required for identification increase

Engineering Contradiction:
Improveantigen specificity assessmentVSAvoidtime for identification
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent incorporates preliminary computational filtering and pre-processing steps that identify and remove low-quality single-cell data before comprehensive analysis. The system performs preliminary clonotype grouping and antigen specificity prediction using machine learning algorithms that can rapidly screen large datasets, thereby reducing the time required for thorough antigen-specific population identification while maintaining measurement precision through subsequent validation steps.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS20250266124A1Systems and methods for determining antigen specificity of antigen binding molecules and visualizing adaptive immune cell clonotyping data
Publication Date: 2025.08.21 10X GENOMICS INC
  • US20250266124A1 patent drawing
  • US20250266124A1 patent drawing
  • US20250266124A1 patent drawing

AI summary

Provided herein are computer-implemented methods including receiving, by a processor, a data set comprising cellular data, and presenting an end user with a visualization tool, wherein the cellular data may include at least one of an antigen binding specificity value associated with a cell receptor and a unique molecular identifier (UMI) count associated with the cell receptor. The visualization tool can provide a dynamic display of the data set by generating a visual sequence from the data set, displaying at least a portion of the generated visual sequence, and displaying in response to a user interaction with the visualization tool, the antigen binding specificity value or the UMI associated with the cell receptor in conjunction with the at least a portion of the visual sequence. The visual sequences include sets of indicia corresponding paired chains of the cell receptor.