scirpy.tl.define_clonotypes

scirpy.tl.define_clonotypes(adata, *, key_added='clone_id', distance_key=None, airr_mod='airr', airr_key='airr', chain_idx_key='chain_indices', **kwargs)

Define clonotypes based on CDR3 nucleic acid sequence identity.

As opposed to define_clonotype_clusters() which employs a more flexible definition of clonotype clusters, this function stringently defines clonotypes based on nucleic acid sequence identity. Technically, this function is an alias to define_clonotype_clusters() with different default parameters.

Definition of clonotype(-clusters) follows roughly the following procedure:

1. Create a list of unique receptor configurations. This is useful to collapse heavily expanded clonotypes, leading to many cells with identical CDR3 sequences, to a single entry.

2. Compute a pairwise distance matrix of unique receptor configurations. Unique receptor configurations are matched based on the pre-computed VJ and VDJ distance matrices and the parameters of receptor_arms, dual_ir, same_v_gene and within_group.

3. Find connected modules in the graph defined by this distance matrix. Each connected module is considered a clonotype-cluster.

Parameters:

• adata (Union[AnnData, MuData, DataHandler]) – AnnData or MuData object that contains AIRR information.

• receptor_arms –

  One of the following options:

  • "VJ" - only consider VJ sequences

  • "VDJ" - only consider VDJ sequences

  • "all" - both VJ and VDJ need to match

  • "any" - either VJ or VDJ need to match

  If "any", two distances are combined by taking their minimum. If "all", two distances are combined by taking their maximum. This is motivated by the hypothesis that a receptor recognizes the same antigen if it has a distance smaller than a certain cutoff. If we require only one of the receptors to match ("any") the smaller distance is relevant. If we require both receptors to match ("all"), the larger distance is relevant.

• dual_ir –

  One of the following options:

  • "primary_only" - only consider most abundant pair of VJ/VDJ chains

  • "any" - consider both pairs of VJ/VDJ sequences. Distance must be below cutoff for any of the chains.

  • "all" - consider both pairs of VJ/VDJ sequences. Distance must be below cutoff for all of the chains.

  Distances are combined as for receptor_arms.

  See also Dual IR.

• same_v_gene –

  Enforces clonotypes to have the same V-genes. This is useful as the CDR1 and CDR2 regions are fully encoded in this gene. See CDR for more details.

  v genes are matched based on the behaviour defined with receptor_arms and dual_ir.

• within_group – Enforces clonotypes to have the same group defined by one or multiple grouping variables. Per default, this is set to receptor_type, i.e. clonotypes cannot comprise both B cells and T cells. Set this to receptor_subtype if you don’t want clonotypes to be shared across e.g. gamma-delta and alpha-beta T-cells. You can also set this to any other column in adata.obs that contains a grouping, or to None, if you want no constraints.

• key_added (str (default: 'clone_id')) – The column name under which the clonotype clusters and cluster sizes will be stored in adata.obs and under which the clonotype network will be stored in adata.uns

• inplace – If True, adds the results to anndata, otherwise return them.

• n_jobs – Number of CPUs to use for clonotype cluster calculation. Default: use all cores. If the number of cells is smaller than 2 * chunksize a single worker thread will be used to avoid overhead.

• chunksize – Number of objects to process per chunk. Each worker thread receives data in chunks. Smaller chunks result in a more meaningful progressbar, but more overhead.

• airr_mod (default: 'airr') – Name of the modality with AIRR information is stored in the MuData object. if an AnnData object is passed to the function, this parameter is ignored.

• airr_key (default: 'airr') – Key under which the AIRR information is stored in adata.obsm as an awkward array.

• chain_idx_key (default: 'chain_indices') – Key under which the chain indices are stored in adata.obsm. If chain indices are not present, index_chains() is run with default parameters.

Return type:

Optional[tuple[Series, Series, dict]]

Returns:

clonotype

A Series containing the clonotype id for each cell. Will be stored in adata.obs[key_added] if inplace is True

clonotype_size

A Series containing the number of cells in the respective clonotype for each cell. Will be stored in adata.obs[f"{key_added}_size"] if inplace is True.

distance_result

A dictionary containing

• distances: A sparse, pairwise distance matrix between unique receptor configurations

• cell_indices: A dict of arrays, containing the adata.obs_names (cell indices) for each row in the distance matrix.

If inplace is True, this is added to adata.uns[key_added].