model_representation.rst

Executable models

The BioRECIPE format supports representation of the static graph structure of models, as well as attributes necessary to study the dynamics. Models are represented in the BioRECIPE format using element-based approach.

A toy example of a model graph, including input and output nodes, directed edges, paths, feedback and feedforward loops, and cellular compartments is shown in the introduction.

Model formats

In the BioRECIPE format, each element in a model is assigned a row in the model table/spreadsheet. Different from event-based representation of interactions, in this element-based representation interactions in which the element participates as a regulated element (target node of interaction edge) can be combined into an element update rule. The BioRECIPE format supports several different model representation schemes, ranging from less detailed to more detailed, from static graph attributes to dynamic attributes and parameters necessary for analysis of dynamic behavior, as illustrated in the table below (x indicates attributes included in the representation scheme):

Model attributes

The following tables provide details for each attribute, including attribute name used in the BioRECIPE spreadsheet, a symbol used in detailed definitions, a brief description of the attribute, its allowed values, and a few examples for the attribute. Model examples can be found here.

The basic element (node) attributes, and context attributes are inherited from the interactions in which the element participates (as a regulated element), and they are included in the element representation, as shown in the figure above (columns under Element header).

Several other interaction attributes are ordered lists of values from all individual interactions where the element is a regulated element (target node on the interaction edge). These are referred to as Regulation attributes and include basic and provenance attributes combined from indvidual interactions (basic interaction attributes and provenance attributes).

Regulation attributes - basic

Attribute	Symbol	Description	Format	Examples
Positive regulator list	aposreglist	All positive regulators of the element from individual interactions, combined into a list	<positive regulator 1>, <positive regulator 2>, ..., <positive regulator k>	PDPK1pn_cytoPCC
Positive connection type list	aposconnectiontypelist	All connection types of element's positive regulators from individual interactions, combined into a list, following the same order as in the positive regulator list	<positive connection type 1>, <positive connection type 2>, ..., <positive connection type k>	direct
Positive mechanism list	aposmechanismlist	All mechanisms of element's positive regulators from individual interactions, combined into a list, following the same order as in the positive regulator list	<positive mechanism 1>, <positive mechanism 2>, ..., <positive mechanism k>	phosphorylation
Positive site list	apossitelist	All interaction sites of element's positive regulators from individual interactions, combined into a list, following the same order as in the positive regulator list	<positive site 1>, <positive site 2>, ..., <positive site k>	T308
Negative regulator list	anegreglist	All negative regulators of the element from individual interactions, combined into a list	<negative regulator 1>, <negative regulator 2>, ..., <negative regulator l>	ICMTpn_erPCC, PP2Apf_cytoPCC
Negative connection type list	anegconnectiontypelist	All connection types of element's negative regulators from individual interactions, combined into a list, following the same order as in the negative regulator list	<negative connection type 1>, <negative connection type 2>, ..., <negative connection type l>	indirect, direct
Negative mechanism list	anegmechanismlist	All mechanisms of element's negative regulators from individual interactions, combined into a list, following the same order as in the negative regulator list	<negative mechanism 1>, <negative mechanism 2>, ..., <negative mechanism l>	N/A, dephosphorylation
Negative site list	anegsitelist	All interaction sites of element's negative regulators from individual interactions, combined into a list, following the same order as in the negative regulator list	<negative site 1>, <negative site 2>, ..., <negative site l>	N/A, T308

Regulation attributes - provenance

Attribute	Symbol	Description	Format	Examples
Score list	ascorelist	all scores of element's positive and negative regulations from individual interactions, combined into a list, following the order of positive and then negative regulator lists	<score 1>, <score 2>, ..., <score k + l>	1,1,1
Source list	asourcelist	all sources of element's positive and negative regulations from individual interactions, combined into a list, following the order of positive and then negative regulator lists	<source 1>, <source 2>, ..., <source k + l>	literature, literature, literature
Statements list	astatementslist	all support statements of element's positive and negative regulations from individual interactions, combined into a list, following the order of positive and then negative regulator lists	<statements 1>, <statements 2>, ..., <statements k + l>	Akt is phosphorylated at its residue Thr308 by the 3-phosphoinositide-dependent protein kinase 1 (PDK1),'We find that PFKFB4 interacts with ICMT, a posttranslational modifier of RAS. PFKFB4 promotes ICMT/RAS interaction, controls RAS localization at the plasma membrane, activates AKT signaling and enhances cell migration.','The protein phosphatase 2A (PP2A) has long been known to negatively regulate Akt activity.'
Paper IDs list	apaperIDslist	all paper IDs (where statements are found) of element's positive and negative regulations from individual interactions, combined into a list, following the order of positive and then negative regulator lists	<paper IDs 1>, <paper IDs 2>, ..., <paper IDs k + l>	PMC6518649, PMC9348664, PMC10332018

Whenever an individual regulator (positive or negative) has an empty attribute value, this is indicated with None in the list of attribute values.

Finally, several new model attributes are included in executable models to define element update rules, as well as element value and timing parameters for the simulation. These attributes are included under Simulation parameters in the figure above. More details on how these parameters are used in simulation can be found int the DiSH simulator documentation.

Simulation attributes - rule

Attribute	Symbol	Description	Format or Values	Examples
Variable	avariable	Variable name assigned to model element used by simulators and other software	<variable_name>	AKTpf_cytoPCC
Positive regulation rule	aposregrule	A rule used in simulation to compute the level of element's positive regulation	<string> //The rules for creating these positive regulation strings are written separately.	PDPK1pn_cytoPCC
Negative regulation rule	anegregurule	A rule used in simulation to compute the level of element's negative regulation	<string> //The rules for creating these negative regulation strings are written separately.	(ICMTpn_erPCC, PP2Apf_cytoPCC)

Simulation attributes - value

Attribute	Symbol	Description	Format or Values	Examples
Value type	avaluetype	Type of value used for interpretting model outcomes	amount | activity	amount
Levels	alevels	Number of different levels (values) an element can be assigned; or infinite if a continuous variable	<number of distinct levels> | inf	4
State list number	astatelist	State list used in simulation to initialize the element and assign values throughout simulation; multiple state lists can be included and numbered, starting from 0	<value>,<value>[time],...,<value>[time]	1
Const OFF	aconstOFF	Indicates whether the element is assumed to be at the lowest allowed level (usually 0) for the entire simulation	empty | ✓	value you choose
Const ON	aconstON	Indicates whether the element is assumed to be at the highest allowed level for the entire simulation	empty | ✓	value you choose
Increment	aincrement	When the element can have more than two different levels, an increment indicates by how many levels it is allowed to increase or decrease in a single time step	Δvalue	1

Simulation attributes - timing

Attribute	Symbol	Description	Format or Values	Examples
Spontaneous	aspontaneous	Specifies spontaneous behavior of the element, if it has only positive or only negative regulators	<non-negative integer> | None	None
Balancing	abalancing	Specifies the behavior of the element when its positive and negative regulation levels are equal	{increase, <non-negative integer>} | {decrease, <non-negative integer>} | None	decrease,0
Delay	adelay	description	definition	0,0,100,0,0
Update group	aupdategroup	description	definition	1
Update rate	aupdaterate	description	definition	1
Update rank	aupdaterank	description	definition	1