INDRA Statements (indra.statements)

Statements represent mechanistic relationships between biological agents.

Statement classes follow an inheritance hierarchy, with all Statement types inheriting from the parent class Statement. At the next level in the hierarchy are the following classes:

There are several types of Statements representing post-translational modifications that further inherit from Modification:

There are additional subtypes of SelfModification:

Interactions between proteins are often described simply in terms of their effect on a protein’s “activity”, e.g., “Active MEK activates ERK”, or “DUSP6 inactives ERK”. These types of relationships are indicated by the RegulateActivity abstract base class which has subtypes

while the RegulateAmount abstract base class has subtypes

Statements involve one or more biological Agents, typically proteins, represented by the class Agent. Agents can have several types of context specified on them including

The active form of an agent (in terms of its post-translational modifications or bound state) is indicated by an instance of the class ActiveForm.

Agents also carry grounding information which links them to database entries. These database references are represented as a dictionary in the db_refs attribute of each Agent. The dictionary can have multiple entries. For instance, INDRA’s input Processors produce genes and proteins that carry both UniProt and HGNC IDs in db_refs, whenever possible. Bioentities provides a name space for protein families that are typically used in the literature. More information about Bioentities can be found here: https://github.com/sorgerlab/bioentities

Type Database Example
Gene/Protein HGNC {‘HGNC’: ‘11998’}
Gene/Protein UniProt {‘UP’: ‘P04637’}
Gene/Protein family Bioentities {‘BE’: ‘ERK’}
Gene/Protein family InterPro {‘IP’: ‘IPR000308’}
Gene/Protein family Pfam {‘PF’: ‘PF00071’}
Gene/Protein family NextProt family {‘NXPFAM’: ‘03114’}
Chemical ChEBI {‘CHEBI’: ‘CHEBI:63637’}
Chemical PubChem {‘PUBCHEM’: ‘42611257’}
Metabolite HMDB {‘HMDB’: ‘HMDB00122’}
Process, location, etc. GO {‘GO’: ‘GO:0006915‘}
Process, disease, etc. MeSH {‘MESH’: ‘D008113’}
General terms NCIT {‘NCIT’: ‘C28597’}
Raw text TEXT {‘TEXT’: ‘Nf-kappaB’}

The evidence for a given Statement, which could include relevant citations, database identifiers, and passages of text from the scientific literature, is contained in one or more Evidence objects associated with the Statement.

class indra.statements.Acetylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Acetylation modification.

class indra.statements.Activation(subj, obj, obj_activity='activity', evidence=None)[source]

Bases: indra.statements.RegulateActivity

Indicates that a protein activates another protein.

This statement is intended to be used for physical interactions where the mechanism of activation is not explicitly specified, which is often the case for descriptions of mechanisms extracted from the literature.

Parameters:
  • subj (Agent) – The agent responsible for the change in activity, i.e., the “upstream” node.
  • obj (Agent) – The agent whose activity is influenced by the subject, i.e., the “downstream” node.
  • obj_activity (Optional[str]) – The activity of the obj Agent that is affected, e.g., its “kinase” activity.
  • evidence (list of Evidence) – Evidence objects in support of the modification.

Examples

MEK (MAP2K1) activates the kinase activity of ERK (MAPK1):

>>> mek = Agent('MAP2K1')
>>> erk = Agent('MAPK1')
>>> act = Activation(mek, erk, 'kinase')
class indra.statements.ActiveForm(agent, activity, is_active, evidence=None)[source]

Bases: indra.statements.Statement

Specifies conditions causing an Agent to be active or inactive.

Types of conditions influencing a specific type of biochemical activity can include modifications, bound Agents, and mutations.

Parameters:
  • agent (Agent) – The Agent in a particular active or inactive state. The sets of ModConditions, BoundConditions, and MutConditions on the given Agent instance indicate the relevant conditions.
  • activity (str) – The type of activity influenced by the given set of conditions, e.g., “kinase”.
  • is_active (bool) – Whether the conditions are activating (True) or inactivating (False).
class indra.statements.ActivityCondition(activity_type, is_active)[source]

Bases: object

An active or inactive state of a protein.

Examples

Kinase-active MAP2K1:

>>> mek_active = Agent('MAP2K1',
...                    activity=ActivityCondition('kinase', True))

Transcriptionally inactive FOXO3:

>>> foxo_inactive = Agent('FOXO3',
...                     activity=ActivityCondition('transcription', False))
Parameters:
  • activity_type (str) – The type of activity, e.g. ‘kinase’. The basic, unspecified molecular activity is represented as ‘activity’. Examples of other activity types are ‘kinase’, ‘phosphatase’, ‘catalytic’, ‘transcription’, etc.
  • is_active (bool) – Specifies whether the given activity type is present or absent.
class indra.statements.Agent(name, mods=None, activity=None, bound_conditions=None, mutations=None, location=None, db_refs=None)[source]

Bases: object

A molecular entity, e.g., a protein.

Parameters:
  • name (str) – The name of the agent, preferably a canonicalized name such as an HGNC gene name.
  • mods (list of ModCondition) – Modification state of the agent.
  • bound_conditions (list of BoundCondition) – Other agents bound to the agent in this context.
  • mutations (list of MutCondition) – Amino acid mutations of the agent.
  • activity (ActivityCondition) – Activity of the agent.
  • location (str) – Cellular location of the agent. Must be a valid name (e.g. “nucleus”) or identifier (e.g. “GO:0005634”)for a GO cellular compartment.
  • db_refs (dict) – Dictionary of database identifiers associated with this agent.
class indra.statements.Autophosphorylation(enz, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.SelfModification

Intramolecular autophosphorylation, i.e., in cis.

Examples

p38 bound to TAB1 cis-autophosphorylates itself (see PMID:19155529).

>>> tab1 = Agent('TAB1')
>>> p38_tab1 = Agent('P38', bound_conditions=[BoundCondition(tab1)])
>>> autophos = Autophosphorylation(p38_tab1)
class indra.statements.BoundCondition(agent, is_bound=True)[source]

Bases: object

Identify Agents bound (or not bound) to a given Agent in a given context.

Parameters:
  • agent (Agent) – Instance of Agent.
  • is_bound (bool) – Specifies whether the given Agent is bound or unbound in the current context. Default is True.

Examples

EGFR bound to EGF:

>>> egf = Agent('EGF')
>>> egfr = Agent('EGFR', bound_conditions=[BoundCondition(egf)])

BRAF not bound to a 14-3-3 protein (YWHAB):

>>> ywhab = Agent('YWHAB')
>>> braf = Agent('BRAF', bound_conditions=[BoundCondition(ywhab, False)])
class indra.statements.Complex(members, evidence=None)[source]

Bases: indra.statements.Statement

A set of proteins observed to be in a complex.

Parameters:members (list of Agent) – The set of proteins in the complex.

Examples

BRAF is observed to be in a complex with RAF1:

>>> braf = Agent('BRAF')
>>> raf1 = Agent('RAF1')
>>> cplx = Complex([braf, raf1])
class indra.statements.Conversion(subj, obj_from=None, obj_to=None, evidence=None)[source]

Bases: indra.statements.Statement

Conversion of molecular species mediated by a controller protein.

Parameters:
  • subj (:py:class`indra.statement.Agent`) – The protein mediating the conversion.
  • obj_from (list of indra.statement.Agent) – The list of molecular species being consumed by the conversion.
  • obj_to (list of indra.statement.Agent) – The list of molecular species being created by the conversion.
  • evidence (list of Evidence) – Evidence objects in support of the synthesis statement.
class indra.statements.Deacetylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Deacetylation modification.

class indra.statements.DecreaseAmount(subj, obj, evidence=None)[source]

Bases: indra.statements.RegulateAmount

Degradation of a protein, possibly mediated by another protein.

Note that this statement can also be used to represent inhibitors of synthesis (e.g., cycloheximide).

Parameters:
  • subj (:py:class`indra.statement.Agent`) – The protein mediating the degradation.
  • obj (indra.statement.Agent) – The protein that is degraded.
  • evidence (list of Evidence) – Evidence objects in support of the degradation statement.
class indra.statements.Defarnesylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Defarnesylation modification.

class indra.statements.Degeranylgeranylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Degeranylgeranylation modification.

class indra.statements.Deglycosylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Deglycosylation modification.

class indra.statements.Dehydroxylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Dehydroxylation modification.

class indra.statements.Demethylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Demethylation modification.

class indra.statements.Demyristoylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Demyristoylation modification.

class indra.statements.Depalmitoylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Depalmitoylation modification.

class indra.statements.Dephosphorylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Dephosphorylation modification.

Examples

DUSP6 dephosphorylates ERK (MAPK1) at T185:

>>> dusp6 = Agent('DUSP6')
>>> erk = Agent('MAPK1')
>>> dephos = Dephosphorylation(dusp6, erk, 'T', '185')
class indra.statements.Deribosylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Deribosylation modification.

class indra.statements.Desumoylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Desumoylation modification.

class indra.statements.Deubiquitination(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.RemoveModification

Deubiquitination modification.

class indra.statements.Evidence(source_api=None, source_id=None, pmid=None, text=None, annotations=None, epistemics=None)[source]

Bases: object

Container for evidence supporting a given statement.

Parameters:
  • source_api (str or None) – String identifying the INDRA API used to capture the statement, e.g., ‘trips’, ‘biopax’, ‘bel’.
  • source_id (str or None) – For statements drawn from databases, ID of the database entity corresponding to the statement.
  • pmid (str or None) – String indicating the Pubmed ID of the source of the statement.
  • text (str) – Natural language text supporting the statement.
  • annotations (dict) – Dictionary containing additional information on the context of the statement, e.g., species, cell line, tissue type, etc. The entries may vary depending on the source of the information.
  • epistemics (dict) – A dictionary describing various forms of epistemic certainty associated with the statement.
class indra.statements.Farnesylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Farnesylation modification.

class indra.statements.Gap(gap, ras, evidence=None)[source]

Bases: indra.statements.Statement

Acceleration of a GTPase protein’s GTP hydrolysis rate by a GAP.

Represents the generic process by which a GTPase activating protein (GAP) catalyzes GTP hydrolysis by a particular small GTPase protein.

Parameters:
  • gap (Agent) – The GTPase activating protein.
  • ras (Agent) – The GTPase protein.

Examples

RASA1 catalyzes GTP hydrolysis on KRAS:

>>> rasa1 = Agent('RASA1')
>>> kras = Agent('KRAS')
>>> gap = Gap(rasa1, kras)
class indra.statements.Gef(gef, ras, evidence=None)[source]

Bases: indra.statements.Statement

Exchange of GTP for GDP on a small GTPase protein mediated by a GEF.

Represents the generic process by which a guanosine exchange factor (GEF) catalyzes nucleotide exchange on a GTPase protein.

Parameters:
  • gef (Agent) – The guanosine exchange factor.
  • ras (Agent) – The GTPase protein.

Examples

SOS1 catalyzes nucleotide exchange on KRAS:

>>> sos = Agent('SOS1')
>>> kras = Agent('KRAS')
>>> gef = Gef(sos, kras)
class indra.statements.Geranylgeranylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Geranylgeranylation modification.

class indra.statements.Glycosylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Glycosylation modification.

class indra.statements.HasActivity(agent, activity, has_activity, evidence=None)[source]

Bases: indra.statements.Statement

States that an Agent has or doesn’t have a given activity type.

With this Statement, one cane express that a given protein is a kinase, or, for instance, that it is a transcription factor. It is also possible to construct negative statements with which one epxresses, for instance, that a given protein is not a kinase.

Parameters:
  • agent (Agent) – The Agent that that statement is about. Note that the detailed state of the Agent is not relevant for this type of statement.
  • activity (str) – The type of activity, e.g., “kinase”.
  • has_activity (bool) – Whether the given Agent has the given activity (True) or not (False).
class indra.statements.Hydroxylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Hydroxylation modification.

class indra.statements.IncreaseAmount(subj, obj, evidence=None)[source]

Bases: indra.statements.RegulateAmount

Synthesis of a protein, possibly mediated by another protein.

Parameters:
  • subj (:py:class`indra.statement.Agent`) – The protein mediating the synthesis.
  • obj (indra.statement.Agent) – The protein that is synthesized.
  • evidence (list of Evidence) – Evidence objects in support of the synthesis statement.
class indra.statements.Inhibition(subj, obj, obj_activity='activity', evidence=None)[source]

Bases: indra.statements.RegulateActivity

Indicates that a protein inhibits or deactivates another protein.

This statement is intended to be used for physical interactions where the mechanism of inhibition is not explicitly specified, which is often the case for descriptions of mechanisms extracted from the literature.

Parameters:
  • subj (Agent) – The agent responsible for the change in activity, i.e., the “upstream” node.
  • obj (Agent) – The agent whose activity is influenced by the subject, i.e., the “downstream” node.
  • obj_activity (Optional[str]) – The activity of the obj Agent that is affected, e.g., its “kinase” activity.
  • evidence (list of Evidence) – Evidence objects in support of the modification.
exception indra.statements.InvalidLocationError(name)[source]

Bases: ValueError

Invalid cellular component name.

exception indra.statements.InvalidResidueError(name)[source]

Bases: ValueError

Invalid residue (amino acid) name.

class indra.statements.Methylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Methylation modification.

class indra.statements.ModCondition(mod_type, residue=None, position=None, is_modified=True)[source]

Bases: object

Post-translational modification state at an amino acid position.

Parameters:
  • mod_type (str) – The type of post-translational modification, e.g., ‘phosphorylation’. Valid modification types currently include: ‘phosphorylation’, ‘ubiquitination’, ‘sumoylation’, ‘hydroxylation’, and ‘acetylation’. If an invalid modification type is passed an InvalidModTypeError is raised.
  • residue (str or None) – String indicating the modified amino acid, e.g., ‘Y’ or ‘tyrosine’. If None, indicates that the residue at the modification site is unknown or unspecified.
  • position (str or None) – String indicating the position of the modified amino acid, e.g., ‘202’. If None, indicates that the position is unknown or unspecified.
  • is_modified (bool) – Specifies whether the modification is present or absent. Setting the flag specifies that the Agent with the ModCondition is unmodified at the site.

Examples

Doubly-phosphorylated MEK (MAP2K1):

>>> phospho_mek = Agent('MAP2K1', mods=(
... ModCondition('phosphorylation', 'S', '202'),
... ModCondition('phosphorylation', 'S', '204')))

ERK (MAPK1) unphosphorylated at tyrosine 187:

>>> unphos_erk = Agent('MAPK1', mods=(
... ModCondition('phosphorylation', 'Y', '187', is_modified=False)))
class indra.statements.Modification(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.Statement

Generic statement representing the modification of a protein.

Parameters:
  • enz (:py:class`indra.statement.Agent`) – The enzyme involved in the modification.
  • sub (indra.statement.Agent) – The substrate of the modification.
  • residue (str or None) – The amino acid residue being modified, or None if it is unknown or unspecified.
  • position (str or None) – The position of the modified amino acid, or None if it is unknown or unspecified.
  • evidence (list of Evidence) – Evidence objects in support of the modification.
class indra.statements.MutCondition(position, residue_from, residue_to=None)[source]

Bases: object

Mutation state of an amino acid position of an Agent.

Parameters:
  • position (str) – Residue position of the mutation in the protein sequence.
  • residue_from (str) – Wild-type (unmodified) amino acid residue at the given position.
  • residue_to (str) – Amino acid at the position resulting from the mutation.

Examples

Represent EGFR with a L858R mutation:

>>> egfr_mutant = Agent('EGFR', mutations=(MutCondition('858', 'L', 'R')))
class indra.statements.Myristoylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Myristoylation modification.

class indra.statements.Palmitoylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Palmitoylation modification.

class indra.statements.Phosphorylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Phosphorylation modification.

Examples

MEK (MAP2K1) phosphorylates ERK (MAPK1) at threonine 185:

>>> mek = Agent('MAP2K1')
>>> erk = Agent('MAPK1')
>>> phos = Phosphorylation(mek, erk, 'T', '185')
class indra.statements.RegulateActivity[source]

Bases: indra.statements.Statement

Regulation of activity.

This class implements shared functionality of Activation and Inhibition statements and it should not be instantiated directly.

class indra.statements.RegulateAmount(subj, obj, evidence=None)[source]

Bases: indra.statements.Statement

Superclass handling operations on directed, two-element interactions.

class indra.statements.Ribosylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Ribosylation modification.

class indra.statements.SelfModification(enz, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.Statement

Generic statement representing the self-modification of a protein.

Parameters:
  • enz (:py:class`indra.statement.Agent`) – The enzyme involved in the modification, which is also the substrate.
  • residue (str or None) – The amino acid residue being modified, or None if it is unknown or unspecified.
  • position (str or None) – The position of the modified amino acid, or None if it is unknown or unspecified.
  • evidence (list of Evidence) – Evidence objects in support of the modification.
class indra.statements.Statement(evidence=None, supports=None, supported_by=None)[source]

Bases: object

The parent class of all statements.

Parameters:
  • evidence (list of Evidence) – If a list of Evidence objects is passed to the constructor, the value is set to this list. If a bare Evidence object is passed, it is enclosed in a list. If no evidence is passed (the default), the value is set to an empty list.
  • supports (list of Statement) – Statements that this Statement supports.
  • supported_by (list of Statement) – Statements supported by this statement.
to_graph()[source]

Return Statement as a networkx graph.

to_json()[source]

Return serialized Statement as a json dict.

class indra.statements.Sumoylation(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Sumoylation modification.

class indra.statements.Translocation(agent, from_location=None, to_location=None, evidence=None)[source]

Bases: indra.statements.Statement

The translocation of a molecular agent from one location to another.

Parameters:
  • agent (Agent) – The agent which translocates.
  • from_location (Optional[str]) – The location from which the agent translocates. This must be a valid GO cellular component name (e.g. “cytoplasm”) or ID (e.g. “GO:0005737”).
  • to_location (Optional[str]) – The location to which the agent translocates. This must be a valid GO cellular component name or ID.
class indra.statements.Transphosphorylation(enz, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.SelfModification

Autophosphorylation in trans.

Transphosphorylation assumes that a kinase is already bound to a substrate (usually of the same molecular species), and phosphorylates it in an intra-molecular fashion. The enz property of the statement must have exactly one bound_conditions entry, and we assume that enz phosphorylates this molecule. The bound_neg property is ignored here.

class indra.statements.Ubiquitination(enz, sub, residue=None, position=None, evidence=None)[source]

Bases: indra.statements.AddModification

Ubiquitination modification.

indra.statements.get_valid_location(location)[source]

Check if the given location represents a valid cellular component.

indra.statements.get_valid_residue(residue)[source]

Check if the given string represents a valid amino acid residue.