Relationships in the GO

Alex Warwick Vesztrocy, March 2016

For some analyses, it is possible to only use the is_a definitions given in the Gene Ontology.

However, it is important to remember that this isn’t always the case. As such, GOATOOLS includes the option to load the relationship definitions also.

Loading GO graph with the relationship tags

This is possible by using the optional_attrs argument, upon instantiating a GODag.

import os
from goatools.obo_parser import GODag

if not os.path.exists('go-basic.obo'):
    !wget http://geneontology.org/ontology/go-basic.obo
go = GODag('go-basic.obo', optional_attrs=['relationship'])

go-basic.obo: fmt(1.2) rel(2019-04-17) 47,398 GO Terms; optional_attrs(relationship)

## Viewing relationships in the GO graph

So now, when looking at an individual term (which has a relationship defined in the GO) these are listed in a nested manner. As an example, look at GO:1901990 which has a single regulates relationship.

eg_term = go['GO:1901990']

eg_term

GOTerm('GO:1901990'):
  id:GO:1901990
  item_id:GO:1901990
  name:regulation of mitotic cell cycle phase transition
  namespace:biological_process
  _parents: 2 items
    GO:1901987
    GO:0007346
  parents: 2 items
    GO:1901987	level-06	depth-06	regulation of cell cycle phase transition [biological_process]
    GO:0007346	level-05	depth-05	regulation of mitotic cell cycle [biological_process]
  children: 6 items
    GO:1901991	level-07	depth-08	negative regulation of mitotic cell cycle phase transition [biological_process]
    GO:0010389	level-07	depth-08	regulation of G2/M transition of mitotic cell cycle [biological_process]
    GO:1901992	level-07	depth-08	positive regulation of mitotic cell cycle phase transition [biological_process]
    GO:0007096	level-07	depth-08	regulation of exit from mitosis [biological_process]
    GO:2000045	level-07	depth-08	regulation of G1/S transition of mitotic cell cycle [biological_process]
    GO:0030071	level-07	depth-10	regulation of mitotic metaphase/anaphase transition [biological_process]
  level:6
  depth:7
  is_obsolete:False
  alt_ids: 0 items
  relationship: 1 items
    regulates: 1 items
      GO:0044772	level-04	depth-04	mitotic cell cycle phase transition [biological_process]
  relationship_rev: 0 items
  reldepth:7

These different relationship types are stored as a dictionary within the relationship attribute on a GO term.

print(eg_term.relationship.keys())

dict_keys(['regulates'])

print(eg_term.relationship['regulates'])

{GOTerm('GO:0044772'):
  id:GO:0044772
  item_id:GO:0044772
  name:mitotic cell cycle phase transition
  namespace:biological_process
  _parents: 2 items
    GO:0044770
    GO:1903047
  parents: 2 items
    GO:0044770	level-03	depth-03	cell cycle phase transition [biological_process]
    GO:1903047	level-03	depth-03	mitotic cell cycle process [biological_process]
  children: 4 items
    GO:0007091	level-05	depth-10	metaphase/anaphase transition of mitotic cell cycle [biological_process]
    GO:0010458	level-05	depth-05	exit from mitosis [biological_process]
    GO:0000082	level-05	depth-05	G1/S transition of mitotic cell cycle [biological_process]
    GO:0000086	level-05	depth-05	G2/M transition of mitotic cell cycle [biological_process]
  level:4
  depth:4
  is_obsolete:False
  alt_ids: 0 items
  relationship: 0 items
  relationship_rev: 3 items
    regulates: 1 items
      GO:1901990	level-06	depth-07	regulation of mitotic cell cycle phase transition [biological_process]
    negatively_regulates: 1 items
      GO:1901991	level-07	depth-08	negative regulation of mitotic cell cycle phase transition [biological_process]
    positively_regulates: 1 items
      GO:1901992	level-07	depth-08	positive regulation of mitotic cell cycle phase transition [biological_process]
  reldepth:5}

Example use case

One example use case for the relationship terms, would be to look for all functions which regulate pseudohyphal growth (GO:0007124). That is:

A pattern of cell growth that occurs in conditions of nitrogen limitation and abundant fermentable carbon source. Cells become elongated, switch to a unipolar budding pattern, remain physically attached to each other, and invade the growth substrate.

Source: https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0007124#term=info&info=1

term_of_interest = go['GO:0007124']

First, find the relationship types which contain “regulates”:

regulates = frozenset([typedef 
                       for typedef in go.typedefs.keys() 
                       if 'regulates' in typedef])
print(regulates)

frozenset({'positively_regulates', 'regulates', 'negatively_regulates'})

Now, search through the terms in the tree for those with a relationship in this list and add them to a dictionary dependent on the type of regulation.

from collections import defaultdict

regulating_terms = defaultdict(list)

for t in go.values():
    if hasattr(t, 'relationship'):
        for typedef in regulates.intersection(t.relationship.keys()):
            if term_of_interest in t.relationship[typedef]:
                regulating_terms['{:s}d_by'.format(typedef[:-1])].append(t)

Now regulating_terms contains the GO terms which relate to regulating protein localisation to the nucleolus.

print('{:s} ({:s}) is:'.format(term_of_interest.name, term_of_interest.id))
for regulate_desc, goterms in regulating_terms.items():
    print('\n  - {:s}:'.format(regulate_desc))
    for goterm in goterms:
        print('    -- {:s} {:s}'.format(goterm.id, goterm.name))
        for gochild in goterm.children:
            print('    -- {:s} {:s}'.format(gochild.id, gochild.name))

pseudohyphal growth (GO:0007124) is:

  - regulated_by:
    -- GO:2000220 regulation of pseudohyphal growth
    -- GO:2000222 positive regulation of pseudohyphal growth
    -- GO:2000221 negative regulation of pseudohyphal growth

  - negatively_regulated_by:
    -- GO:2000221 negative regulation of pseudohyphal growth
    -- GO:1900462 negative regulation of pseudohyphal growth by negative regulation of transcription from RNA polymerase II promoter
    -- GO:0100042 negative regulation of pseudohyphal growth by transcription from RNA polymerase II promoter

  - positively_regulated_by:
    -- GO:2000222 positive regulation of pseudohyphal growth
    -- GO:0100041 positive regulation of pseudohyphal growth by transcription from RNA polymerase II promoter
    -- GO:1900461 positive regulation of pseudohyphal growth by positive regulation of transcription from RNA polymerase II promoter