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).

Table 7 Regulation attributes - basic

Attribute	Symbol	Description	Values	Examples
Positive regulator list	\(a^{\mathrm{posreglist}}\)	All positive regulators of the element from individual interactions, combined into a list	<positive regulator 1>, <positive regulator 2>, …, <positive regulator \(k\)>	examples
Positive connection type list	\(a^{\mathrm{posconnectiontypelist}}\)	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 \(k\)>	examples
Positive mechanism list	\(a^{\mathrm{posmechanismlist}}\)	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 \(k\)>	examples
Positive site list	\(a^{\mathrm{possitelist}}\)	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 \(k\)>	examples
Negative regulator list	\(a^{\mathrm{negreglist}}\)	All negative regulators of the element from individual interactions, combined into a list	<negative regulator 1>, <negative regulator 2>, …, <negative regulator \(l\)>	examples
Negative connection type list	\(a^{\mathrm{negconnectiontypelist}}\)	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 \(l\)>	examples
Negative mechanism list	\(a^{\mathrm{negmechanismlist}}\)	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 \(l\)>	examples
Negative site list	\(a^{\mathrm{negsitelist}}\)	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 \(l\)>	examples

Table 8 Regulation attributes - provenance

Attribute	Symbol	Description	Values	Examples
Score list	\(a^{\mathrm{scorelist}}\)	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 \(k+l\)>	examples
Source list	\(a^{\mathrm{sourcelist}}\)	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 \(k+l\)>	examples
Statements list	\(a^{\mathrm{statementslist}}\)	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 \(k+l\)>	examples
Paper IDs list	\(a^{\mathrm{paperIDslist}}\)	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 \(k+l\)>	examples

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.

Table 9 Simulation attributes - rule

Attribute	Symbol	Description	Values	Examples
Variable	\(a^{\mathrm{variable}}\)	Variable name used by simulators and other software	<variable_name>	examples
Positive regulation rule	\(a^{\mathrm{posregrule}}\)	A rule used by simulation to compute the level of element’s positive regulation	<string> //The rules for creating these positive regulation strings are written separately.	examples
Negative regulation rule	\(a^{\mathrm{negregurule}}\)	A rule used by simulation to compute the level of element’s negative regulation	<string> //The rules for creating these negative regulation strings are written separately.	examples

Table 10 Simulation attributes - value

Attribute	Symbol	Description	Values	Examples
Value type	\(a^{\mathrm{valuetype}}\)	Type of value used for interpretting model outcomes	amount | activity	examples
Levels	\(a^{\mathrm{levels}}\)	Number of different levels (values) an element can be assigned; or infinite if a continuous variable	<number of distinct levels> | inf	examples
State list number	\(a^{\mathrm{statelist}}\)	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]	examples
Const OFF	\(a^{\mathrm{constOFF}}\)	Indicates whether the element is assumed to be at the lowest allowed level (usually 0) for the entire simulation	empty | \(\checkmark\)	examples
Const ON	\(a^{\mathrm{constON}}\)	Indicates whether the element is assumed to be at the highest allowed level for the entire simulation	empty | \(\checkmark\)	examples
Increment	\(a^{\mathrm{increment}}\)	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	\(\Delta \mathrm{value}\)	examples

Table 11 Simulation attributes - timing

Attribute	Symbol	Description	Values	Examples
Spontaneous	\(a^{\mathrm{spontaneous}}\)	Specifies spontaneous behavior of the element, if it has only positive or only negative regulators	<non-negative integer> | None	examples
Balancing	\(a^{\mathrm{balancing}}\)	Specifies the behavior of the element when its positive and negative regulation levels are equal	{increase <non-negative integer>} | {decrease <non-negative integer>} | None	examples
Delay	\(a^{\mathrm{delay}}\)	description	definition	examples
Update group	\(a^{\mathrm{updategroup}}\)	description	definition	examples
Update rate	\(a^{\mathrm{updaterate}}\)	description	definition	examples
Update rank	\(a^{\mathrm{updaterank}}\)	description	definition	examples