Connectivity

Connectivity#

Protein connectivity reflects how many known biological processes in which a protein is involved if known protein-protein interaction (PPI) databases are used. TMKit is powerful in studying protein connectivity as it not only detect the interaction partners but also confirm how many subunits in a protein complex (where it resides) interact with it.

In tutorials BioGRID and IntAct, we have shown how to access the PPI databases. We can now use the combination of them to study protein connectivity.

TMKit offers an interface, tmkit.ppi, to access the database. In this tutorial, we will show how we can use this database in Python, starting from downloading it.

Example usage#

First, we can define some file paths in ppi_db_fpns as shown below, where BioGRID (BIOGRID-ALL-4.4.212.biogrid) and IntAct (interA_B.intact) can be found.

ppi_db_fpns = {
    'biogrid': 'data/ppi/BIOGRID-ALL-4.4.212.biogrid',
    'intact': 'data/ppi/interA_B.intact',
}

Then, using the following codes, you can generate the interaction partners of a given protein 3pux chain G whose UniProt accession code is P68183. In the PDB structure, there are other 4 chains, A, B, E, and F.

The tmk.ppi.connectivity module will first return all interaction partners of protein 3pux chain G in BioGRID and IntAct, and then return how many chains interact with it. We need to specify a dictionary called interacting_partner_idmap where a PDB code matches an UniProt accession code (e.g., 3pux.A: P68187). Of course, protein 3pux chain G itself is needed to do so 3pux.G: P68183 in prot_idmap.

Their complex structures are needed and the paths to them can be specified using parameters pdb_rcsb_fp and pdb_pdbtm_fp.

Finally, the results will be saved in ./data/ppi/indepdata.ppidb using parameter sv_fpn. It will be like this below.

import tmkit as tmk

df = tmk.ppi.connectivity(
    prot_name='3pux',
    seq_chain='G',
    prot_idmap={'3pux.G': 'P68183'},
    interacting_partner_idmap={
        '3pux.A': 'P68187',
        '3pux.B': 'P68187',
        '3pux.E': 'P0AEX9',
        '3pux.F': 'P02916',
    },
    pdb_rcsb_fp='./data/pdb/rcsb/',
    pdb_pdbtm_fp='./data/pdb/pdbtm/',
    sv_fpn='./data/ppi/indepdata.ppidb',
    ppi_db_fpns=ppi_db_fpns,
)
print(df)

Attributes#

Attribute

Description

prot_name

name of a protein in the prefix of a PDB file name (e.g., 1xqf in 1xqfA.pdb)

seq_chain

chain of a protein in the prefix of a PDB file name (e.g., A in 1xqfA.pdb) (biological purpose)

sv_fp

path to where you want to save files

prot_idmap

a Python dict with key -> value for PDB ID -> UniProt accession code (please see the command below for details)

interacting_partner_idmap

a Python dict with key -> value for PDB ID -> UniProt accession code (please see the command below for details)

pdb_rcsb_fp

path where a target PDB file is placed

pdb_pdbtm_fp

path where a target PDB file is placed

ppi_db_fpns

paths where interaction databases are placed (e.g., BIOGRID-ALL-4.4.212.biogrid and interA_B.intact)

Output#

Finally, you will see the following output. By searching two interaction databases, all interaction partners of protein 3pux chain G are in the second column below.

 ['3pux.G' 'P02916']
 ['3pux.G' 'P02943']
 ['3pux.G' 'P0A8N3']
 ['3pux.G' 'P0AEX9']
 ['3pux.G' 'P0AGH8']
 ['3pux.G' 'P10907']
 ['3pux.G' 'P19576']
 ['3pux.G' 'P33650']
 ['3pux.G' 'P37019']
 ['3pux.G' 'P42907']
 ['3pux.G' 'P68187']
 ['3pux.G' 'P76084']
 ['3pux.G' 'Q46832']
 ['3pux.G' 'chebi:"CHEBI:15422"']
 ['3pux.G' 'chebi:"CHEBI:47785"']

In the same time, the output also tells you that the 4 chains in the complex are all its interacting partners, which you can find via key num_ip_overlapped_db in file ./data/ppi/indepdata.ppidb.

======>basic info:
  prot_name chain pdbtm_chains rcsb_chains source diff   same
0      3pux     G        EFGAB       EFGAB   rcsb       EFGBA
===>UniProt protein id: {'3pux.G': 'P68183'}
===>protein 1 chain 3pux
======>scanning ppi db: biogrid
=========>Record(s) for P68183 found in the left column.
=========>Record(s) for P68183 found in the left column.
======>scanning ppi db: intact
=========>No record(s) for P68183 found in the left column.
=========>Record(s) for P68183 found in the left column.
======>interacting partners from the ppi databases:
[['3pux.G' 'P02916']
 ['3pux.G' 'P02943']
 ['3pux.G' 'P0A8N3']
 ['3pux.G' 'P0AEX9']
 ['3pux.G' 'P0AGH8']
 ['3pux.G' 'P10907']
 ['3pux.G' 'P19576']
 ['3pux.G' 'P33650']
 ['3pux.G' 'P37019']
 ['3pux.G' 'P42907']
 ['3pux.G' 'P68187']
 ['3pux.G' 'P76084']
 ['3pux.G' 'Q46832']
 ['3pux.G' 'chebi:"CHEBI:15422"']
 ['3pux.G' 'chebi:"CHEBI:47785"']]
======>interacting partner idmap: {'3pux.A': 'P68187', '3pux.B': 'P68187', '3pux.E': 'P0AEX9', '3pux.F': 'P02916'}
======>interacting partners from its complex: ['3pux.A', '3pux.B', '3pux.E', '3pux.F']
======>uniprot ids of interacting partners from its complex:['P68187', 'P68187', 'P0AEX9', 'P02916']
======>15 records found from the ppi databases
======>4 interacting partners from its complex
======>4 interacting partners from its complex and found in the ppi databases as well
  prot_name chain pdbtm_chains  ... num_ip ip_chains num_ip_overlapped_db
0      3pux     G        EFGAB  ...    4.0      ABEF                  4.0

[1 rows x 11 columns]
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