DECODE ™
THE ROAD TO DISCOVERY.
THE REPERTOIRE IMMUNE MEDICINES PLATFORMS: DECODING THE DRIVERS
OF IMMUNE RESPONSE
DECODING THE DRIVERS OF IMMUNE RESPONSE 
We have developed a suite of proprietary tools that allow us to interrogate the immune synapse with unprecedented precision. We leverage technologies to understand and predict the presentation of antigens in disease, de-orphan T cell receptors in the context of single-cell phenotype, and curate vast amounts of data to enable deep-learning computational prediction models.

The three platforms at the core of our offering include:

  • MCR: cell-based reporter assays to experimentally quantify peptide-MCH display and de-orphan TCR clonotypes across virtually unlimited peptide-MHC libraries.
  • CIPHER: Tetramer-based assays to measure TCR clonotype, peptide-MHC reactivity and phenotype on a single-cell level.
  • CAPTAN: Deep-learning computational tools to classify platform hits and leverage large datasets to predict TCR reactivity beyond experimental feasibility.




CIPHER™: SOLUBLE, BARCODED MULTIMER pMHC LIBRARIES FOR SINGLE CELL TCR BINDING AND FUNCTIONAL DECODING

Roll over the wheel to learn more about the integration of state-of-the-art technologies for high-throughput interrogation of the immune synapse.

DATA CURATION

Exact pairing of antigen-TCR interactions is contextualized by cell-specific phenotype. Automatic reclaim of data for pipeline execution is connected to machine learning-ready relational databases for further interrogation using our proprietary computational platform.

COMPREHENSIVE ANTIGEN REPRESENTATION

Advanced technology to produce diverse, barcoded pMHC tetramer libraries for focused or broad TCR exploration.

NATIVE TCR DIVERSITY

Deep sampling of primary T cells from blood and tissue.

HUMAN TCR DE-ORPHANING

Staining of T cells with diverse antigen libraries.

CAPTURE OF UNIQUE CELL INFORMATION

Unique cell and molecular barcodes enable TCR, antigen, RNA and surface protein quantification on a single cell level.

HIGH VELOCITY SINGLE CELL PLATFORM

Cells are isolated by encapsulation in droplets. Single cells within these droplet are lysed and the contents reverse transcribed and amplified. Accurate and complete capture of single cell information supports high-throughput discovery flow.

CIPHER™: SOLUBLE, BARCODED MULTIMER pMHC LIBRARIES FOR SINGLE CELL TCR BINDING AND FUNCTIONAL DECODING

MCR™: CHIMERIC MHC/TCR RECEPTORS (MCR) DISPLAYED ON MAMALIAN CELLS ARMED WITH VARIOUS REPORTER SYSTEMS

Roll over  the wheel to learn more about the integration of state-of-the-art technologies for unbiased antigen interrogation of select T cell receptors.

SEQUENCING AND ANTIGEN IDENTIFICATION

The peptide encoding part of the integrated MCR construct is amplified by polymerase chain reaction (PCR) from the isolated DNA. The isolated DNA is sequenced and the antigen-TCR relationship is computationally revealed or analyzed by NGS in bulk.

HIGHLY DIVERSE ANTIGEN REPRESENTATION

Libraries are built at engineered NFAT reporter cells expressing novel pMHC-TCR (MCR) hybrid molecules carrying 106 - 107 cDNA derived peptides.

HUMAN T CELL CLONES

Deep sampling of Activated and memory T cells are isolated from affected tissue and used to generate clones or for TCR cloning. T cells from patient tissue.

DE-ORPHANING OF T CELL RECEPTOR

Co-culture of MCR reporter cells and T cell clones.

CAPTURE OF ACTIVATED REPORTER CELLS

Activated cells are sorted by FACS, expanded and co-cultured again with the same T cell clone.

SINGLE ACTIVATED CELL SORTING

Activated reporter cells are sorted and analyzed individually or by NGS in bulk.

MCR™: CHIMERIC MHC/TCR RECEPTORS (MCR) DISPLAYED ON MAMALIAN CELLS ARMED WITH VARIOUS REPORTER SYSTEMS

CAPTAN™: ADVANCED ANALYTICS
AND DEEP LEARNING TO TURN DATA
INTO INSIGHTS
Roll over the wheel to learn more about how we apply artificial intelligence to three different interfaces in the immune synapse.

PROPRIETERY ANTIGEN-MHC BINDING MODEL

Decreases library sizes by magnitudes, by efficient prediction of which epitopes could present on each MHC allele based on a combination of experimental data on peptide presentation and theoretical definition of pertinent features to explain binding relationships. The model already surpass publicly available algorithms such as netMHC and is continuously updated and trained with experimental data such as folding potential of produced tetramers.

TCR SEQUENCE PROBABILITY

Theory and date driven predictor of T cell sequence generation probability to enable sequencing data interpretation, disease-related TCR selection, and efficient exploration of TCR sequence space for predictive and generative modeling.

T CELL PHENOTYPE DESCRIPTION

Initial modeling to predict current state and future trajectories of an immune cell base on select combinations of gene-expression profiles and surface markers to identify clones based on current cytotoxic and exhaustion status and future potential.

TCR CROSS REACTIVITY ASSESMENT

Description of 3D TCR-peptide-MHC structure using adjacency matrix of pairwise distances. These extremely high-throughput predicted structures can be evaluated by similarity indexes and structure-based affinity prediction models to asses potential cross-reactivity.

AUTOMATIC HIT IDENTIFICATION

Hit browser automatically counts individual tetramer molecules bound to single cells, quantity enrichment of binding within clonotypes relative to controls, identifies and summarizes hits within and across samples for long-range and interactive data analysis

ANTIGEN-MHC-TCR STRUCTURE BINDING PREDICTOR

Using deep learning to combine structural simulations of pMHC-TCR interactions with Cogen’s platform data yields a powerful new approach to decode the immune system. First step towards shifting experimental paradigm from exploratory to confirmatory through predictive and generative modeling.
CAPTAN™: ADVANCED ANALYTICS AND DEEP LEARNING TO TURN DATA INTO INSIGHTS
IMMUNE DECODE LAB (ID LAB)
These technologies make up the core of our Immune Decode Lab (ID Lab), where we utilize best-in-class assays to interrogate immune repertoires in a regulated laboratory environment. We have built and deployed workstreams for:
  • Immune monitoring (T cell repertoire and disease tissue profiling)
  • Patient sub-typing (HLA-typing, tumor transcriptome profiling, pathology, IHC)
  • Discovery (TCR clonotype, peptide-MHC, and phenotype in the context of disease)
  • Product characterization (T cell repertoire analysis, deep characterization of reactivity)
  • Assessment of TCR cross-reactivity using altered peptide ligands