ting - T cell receptor interaction grouping

ting is a tool for clustering large scale T cell receptor repertoires by antigen-specificity

Synopsis

ting [options] -t sample.tsv -r reference.tsv -k kmer.tsv -o output.tsv

Options

Required Input

The user must provide a list of CDR3b sequences.
For compatibility reasons the tab seperated table of TCR sequences required for gliph is supported, too.

    --tcr_sequences tcr_sequences   The format of the table is tab delimited, expecting only the first
                                    column. The header is optional, but if included only use column
                                    names as shown in the example.

    --kmer_file K-MER_FILE          The k-mer file holds all 2-, 3- and 4-mers considered for local
                                    clustering. If file does not exist it will automatically be
                                    generated.

    --reference                     Reference file of naive CDR3 amino acid sequences in fasta-format.
                                    Used as control set by Fisher's exact test.

Example:

CDR3b        TRBV    TRBJ    CDR3a        TRAV        TRAJ    Sample-ID
CAADTSSGANVLTF    TRBV30    TRBJ2-6    CALSDEDTGRRALTF    TRAV19        TRAJ5    09/02171
CAATGGDRAYEQYF    TRBV2    TRBJ2-7    CAASSGANSKLTF    TRAV13-1    TRAJ56    03/04922
CAATQQGETQYF    TRBV2    TRBJ2-5    CAASYGGSARQLTF    TRAV13-1    TRAJ22    02/02591
CACVSNTEAFF    TRBV28    TRBJ1-1    CAGDLNGAGSYQLTF    TRAV25        TRAJ28    PBMC8631
CAGGKGNSPLHF    TRBV2    TRBJ1-6    CVVLRGGSQGNLIF    TRAV12-1    TRAJ42    02/02071
CAGQILAGSDTQYF    TRBV6-4    TRBJ2-3    CATASGNTPLVF    TRAV17        TRAJ29    09/00181
CAGRTGVSTDTQYF    TRBV5-1    TRBJ2-3    CAVTPGGGADGLTF    TRAV41        TRAJ45    02/02591
CAGYTGRANYGYTF    TRBV2    TRBJ1-2    CVVNGGFGNVLHC    TRAV12-1    TRAJ35    01/08733

Optional Input



    --use_structural_boundaries     If set, the first and last three amino acids will be included
                                    in kmer counting and global clustering.

    --no_global                     No global clustering will be performed.

    --no_local                      No local clustering will be performed.

    --min_kmer_occurence            Only kmers which occure at least min_kmer_occurences times in the
                                    sequence sample set will be taken in account. Default is 3.
    
    --max_p_value                   p-value threshold for identifying significant motifs by fisher exact test
    
    --gliph_minp                    probability threshold for identifying significant motifs by gliph test

    --stringent_filtering           Only TCRs starting with a cystein and ending with phenylalanine will be
                                    used (IGMT definition of CDR3 region). Default: False
                                    
    --kmers_gliph                   If set kmers are identified by the non-deterministic approach as implemented by gliph

Install

ting can be run from source or installed via PyPI or bioconda

PiPI:

pip install bio-ting

conda:

conda install -c bioconda bio-ting

Example

Example repertoires can be obtained from repertoires.tar.gz included in the example_data-folder

References have been created by the authors of gliph (Glanville et al.).

ting --tcr_sequences R205-L01-D704D504.tsv --reference reference.fasta --kmer_file R205-L01-D704D504_kmers.tsv -o R205-L01-D704D504_results.tsv

Citation

For citation please refere to our preprint Rapid T cell receptor interaction grouping with ting. A peer review is currently in process.