Welcome to TCRosetta

A comprehensive web server for T-cell receptor sequences analysis and annotation

Introduction

T-cell receptors (TCRs) on T cells' surfaces recognize antigens, respond to recognizing antigens, and play an important role in immunotherapy. Analysis of TCR repertoire helps to understand the immune status and provides new insights for immunotherapy.

TCRosetta is a server for TCR repertoire analysis. Users could use TCRosetta to get a comprehensive feature analysis of their TCR data, including TCR repertoire clonality, diversity, and TRB V/J gene usage. Besides the general statistics, TCRosetta also involves several advanced analyses, like calculating the generation probability of the TRB CDR3 sequence and finding disease-associated CDR3 sequences in the TCR repertoire. Moreover, TCRosetta allows users to annotate the disease condition, cell type, cell source, MHC and peptide information for their data based on manually curated antigen-associated T-cell receptor sequences.

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Overview

TCRosetta is a user-friendly and comprehensive server for analyzing and annotating the TCR repertoire. TCRosetta supports several input formats, including CDR3 sequence list, AIRR-compatible formatted file, ".CSV" formatted file, and output files from TCR extraction software like MiXCR, CATT, IMSEQ and RTCR. The input data will first get through pre-processing to ensure data quality. TCRosetta provides two kinds of analyses for TCR repertoire. The general features analysis include repertoire diversity, CDR3 length distribution, V/J gene usage, V-J gene utilization, and clonality. The functional analysis contain network, public, embedding, and enrichment analyses.

General feature analysis

Some changes like diversity and clonality allow for sensitive tracking of dynamic changes in antigen-specific T-cells and help predict response to immunotherapy. TCRosetta provides general feature analyses for the TCR repertoire: (i) the CDR3 length distribution; (ii) TCR diversity (calculated by Renyi entropy); (iii) the V-J gene utilization; (iv) the sequence logo of the top 100 CDR3 sequences (sort by number of amplifications) in upload sample; (v) the V/J gene usage; (vi) the clonality and its' distribution; (vii) the top 10 CDR3 clonetypes sorted by frequency.

Functional analysis

In TCRosetta, (i) we annotate the disease condition, cell type, cell source, MHC, peptide information of TCR sequences by searching similar complementary determining region 3 (CDR3) sequences of TCR beta chain (TRB). (ii) Identify disease-associated TCR sequences and construct network; (iii) Calculate the generation probability of TCR sequences; (iv) Some statistics preformed on annotation results to obtain disease condition/ cell type / cell source distribution; (v) Visualize the motifs abundance distribution of a TCR repertoire. (vi) Predict peptide-TCR binding.