Compiling domains from various sources

This module provides a function to compile a list of Domain objects for a given protein, using domain data from UniProt, AlphaFold structure predictions, and/or manually specified domains.

Functions:

  • compile_domains: Compiles a list of Domain objects for a given protein

Dependencies:

  • .uniprot_fetch.find_uniprot_domains: For fetching domain data from UniProt.

  • .alphafold_db_domain_identification.read_afdb_json: For reading AlphaFold predicted structure data from the AFDB.

  • .alphafold_db_domain_identification.find_domains_from_pae: For identifying domains from AlphaFold predicted structures.

  • .process_proteins_csv.find_user_specified_domains: For adding manually specified domains from the input dataframe.

alphafragment.domain_compilation.compile_domains(protein, uniprot=True, alphafold=True, manual=True, protein_data=None, pae_method='definite', pae_custom_params=None)

Compiles a list of Domain objects for a given protein, using domain data from UniProt, AlphaFold structure predictions, and/or manually specified domains.

Parameters:

  • proteins (list of Proteins): A list of Protein objects to be fragmented.

  • uniprot (bool, optional): Whether to fetch domain data from UniProt. Defaults to True.

  • alphafold (bool, optional): Whether to use domains identified from AlphaFold sructure predictions for the specified accession code, if available. Defaults to True.

  • manual (bool, optional): Whether to incorporate manually specified domains from the input CSV. Defaults to True.

  • protein_data (pandas.DataFrame): The dataframe containing protein data, including protein names and any manually specified domains. Required if manual is True. Defaults to None.

  • pae_method (str, optional): The method used to identify domains from AlphaFold predicted structures. Options are:

    • ‘cautious’ - Groups residues into domains with moderate PAE thresholds, aiming to balance sensitivity and specificity.

    • ‘definite’ - Only groups residues into domains if there is very high confidence in their relative positions. Likely to produce smaller domains.

    • ‘custom’ - Allows specification of custom PAE thresholds via the custom_params argument.

    Defaults to “definite”.

  • pae_custom_params (dict, optional): Custom PAE thresholds for the AlphaFold domain identification method. Only use with pae_method ‘custom”. Should be a dictionary with the following keys:

    • ‘res_dist_cutoff’ (int) - The residue distance threshold to

    differentiate between close and further residue evaluations. Meaningless if close_pae_val == further_pae_val, or if set below 4 as residues closer than this are ignored anyway due to high base confidence in their relative positions. Set to 10 for cautious grouping method, and irrelavant for definite grouping method as close and further pae_vals are equal.

    • ‘close_pae_val’ (int) - The PAE threshold which residue pairs must fall below to be considered within the same domain, if the distance between them is between 4 and res_dist_cutoff. Set to 4 for cautious grouping method and 2 for definite grouping method.

    • ‘further_pae_val’ (int) - The PAE threshold which residue pairs must fall below to be considered within the same domain, if the distance between them is greater than res_dist_cutoff. Set to 11 for close grouping method and 2 for definite grouping method.

Returns:

  • List of Domain objects: A list of Domain objects, each representing a domain identified in the protein, with ‘type’ indicating the origin of the domain data (‘UniProt’, ‘AlphaFold’, ‘manually_defined’).

Raises:

  • TypeError: If the protein argument is not an instance of the Protein class.

Note:

  • Domain indexing is 0-based, so the start and end positions of the domains will be 1 less than standard residue positions. Manually provided domains are expected to be given in 1-based indexing.