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TCRMatch

Maintainer: Will Chronister, Austin Crinklaw

Please open any issues on Github

Requirements:

  • Linux OS and the g++ compiler
  • Python 3 (to generate certain output)

Installation:

Please download TCRMatch from the latest release and compile from source by running:

make

Usage:

Input

  • A text file containing newline separated CDR3beta amino acid sequences
ASSLRWGDEQY
SADRVGNTLY
ASSFGREQY
ASSQDQVQDTQY
ASSPGQGPYEQY
ATSSGTGAYEQY
ASEAGGSYEQY
ASGDRGADTQY
ASSQAGAYEQY

Alternatively, you may upload files using the AIRR tsv format specified here

To generate the initial scores, please run

./tcrmatch -i input_file -t num_threads [-s threshold] [-d /path/to/database] [-a] > output_file
  • -i specifies the path to the input file
  • -a specifies input file is in AIRR TSV format
  • -t specifies the number of threads to use if operating on more than 1 core
  • -s optional parameter to specify the threshold (default is .97, in alignment with manuscript)
  • -d optional parameter to specify where the database is located, point this to a file of newline separated CDR3b sequences to test your own private set

To update the IEDB_data.tsv file located in the data folder, navigate to the scripts directory and simply run

./update.sh

This creates an archive folder in the top directory "data_archive" and moves the current IEDB_data.tsv file to said directory. This file will be renamed to the current day_month_year_IEDB_data.tsv, and a new version will be downloaded to data/IEDB_data.tsv.

Output

  • Output file has 7 columns in TSV format.
  • First column is the user provided input sequence.
  • Second column contains a CDR3beta sequence from the IEDB scoring higher than the threshold
  • The third column contains the score based on the kernel similarity metric (ranging from threshold to .99)
  • The fourth column contains the epitopes associated with the matched IEDB sequence. If there are multiple, they will be comma separated.
  • The fifth column contains the receptor groups (these can be used to reference the sequences back to the IEDB. If the receptor group is 12843, you can find all the receptors associated by visiting https://iedb.org/receptor/12843)
  • The sixth column contains the name of the specific antigen for the matched receptor
  • The seventh column contains the name of the source organism for the antigen

The last two columns are not always available depending on the data that was curated.

*Note that due to the trimming of IEDB CDR3b sequences, there may be multiple receptor groups that map to the same trimmed sequence. In these cases, the receptor groups will be comma separated and each link to their own unique receptor on the IEDB.

input_sequence match_sequence score epitopes receptor_group antigen source_organism
ASSSRSSYEQY ASSNRSSYEQY 0.97 GILGFVFTL 16861 Matrix protein 1 Influenza A virus
ASSSRSSYEQY ASSARSSYEQY 0.98 GILGFVFTL,RAKFKQLL,GLCTLVAML 53258 Matrix protein 1,Trans-activator protein BZLF1,Transcriptional regulator IE63 homolog Influenza A virus,Human herpesvirus 4 (Epstein Barr virus),Human herpesvirus 4 (Epstein Barr virus)
ASSSRSSYEQY ASSSRASYEQY 0.98 GILGFVFTL,GILGFVFTL 55749,35208 Matrix protein 1,Matrix protein 1 Influenza A virus,Influenza A virus
ASSSRSSYEQY ASSERSSYEQY 0.97 AMKRHGLDNYREYSLGN 21200
ASSSRSSYEQY ASSKRSSYEQY 0.97 GILGFVFTL 41132 Matrix protein 1 Influenza A virus
ASSSRSSYEQY ASSRSSYEQY 0.98 FVCNLLLLFVTVYSHLLLV,GILGFVFTL 120740,13575 ORF3a protein [Severe acute respiratory syndrome coronavirus 2],Matrix protein 1 SARS-CoV2,Influenza A virus
ASSSRSSYEQY ASSQRSSYEQY 0.97 GILGFVFTL,GILGFVFTL 35204,54706 Matrix protein 1,Matrix protein 1 Influenza A virus,Influenza A virus

How it works:

  • TCRMatch implements a similarity metric as defined in arXiv:1205.6031v2
  • Each input sequence is compared to all TCR CDR3beta sequences characterized in the IEDB
  • Sequences that have a score greater than the threshold (.97 by default) are returned as matches

References:

Chronister, William D. et al. "Tcrmatch: Predicting T-Cell Receptor Specificity Based On Sequence Similarity To Previously Characterized Receptors". Frontiers In Immunology, vol 12, 2021. Frontiers Media SA, doi:10.3389/fimmu.2021.640725.

"Towards a Mathematical Foundation of Immunology and Amino Acid Chains" arXiv:1205.6031v2

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