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Virtual Parts Repository 2.0 (VPR2)

Virtual parts are modular and reusable mathematical models of biological parts. Here, we describe various components of VPR2, the new version of the Virtual Parts Repository. The previous version is available at virtualparts.org. VPR2 has a Web-based repository, a Web service and a data layer. Both the Web service and the data layer can be used to connect to different synbio repositories that are enabled by the Synthetic Biology Open Language (SBOL).

Please note that the VPR2 project is under development.

The following sections provides descriptions of VPR2 components and how they can be accessed.

VPR2 Repository

VPR2 has its own data repository and is accessible as a web application. The repository is available at http://virtualparts.org and allows searching for parts, and downloading computational models and genetic descriptions of these parts.

VPR SPARQL Endpoint

The SPARQL endpoint for VPR2 is available at http://virtualparts.org/rdf4j-server/repositories/vpr28. The URL can be used to submit SPARQL queries to VPR2.

VPR2 Web Service (VPR2-WS)

VPR2 web service is REST-based and includes several methdods that can be accessed by computational tools. The development version is available at http://virtualparts.org/virtualparts-ws/webapi. Please see list of available methods as a Web Application Description Language (WADL) file at http://virtualparts.org/virtualparts-ws/webapi/application.wadl.

Please use the VPR2 SPARQL endpoint URL to fetch data from the local VPR2 repository using this web service. The following example uses the command-line curl command to submit requests to the VPR2 web service and relies on the VPR2 SPARQL endpoint:

curl  -X POST "http://virtualparts.org/virtualparts-ws/webapi/component/fetch" -d 'stackuri=http://virtualparts.org/rdf4j-server/repositories/vpr28' -d 'componenturi=http://www.bacillondex.org/BO_31362/1'

VPR2 Web Service Methods

The web service provides methods to retrieve models and information about biological parts and interactions. Some of the web service methods are summarised below.

VPR2 Web Service Client

Although, the Web service can directly be accessed by tools, we also provide a Java client library to facilitate programmatic access. The client library is provided as a single Java Jar file that contain all dependencies and can be downloaded from https://github.com/dissys/vprwiki/releases.

VPR2 Data

VPR2 is a standalone library that can be used to populate SBOL designs with additional details from remote SBOL repositories. VPR2 Data is also included as a dependency as part of the client library and is ideal for users who want to implement their own modelling abstractions. VPR2 Data is available at https://github.com/ICO2S/vpr-data. Data mode

Using the VPR2 Web Service Client

The Web service can be used to create models directly from SBOL files. Basic information about designs in the form of SBOL documents can also be used to retreve detailed information from a specified repository.

Using the library in disconnected mode

This option allows users to specify genetic circuits using SBOL to create models based on the constraints specified. The SBOL designs should include all the biological interactions, except degradation reactions which are added automatically by the VPR2.

The following code creates an SBML model using an SBOL design as a parameter. The SBML model is specified in the SBML Level 3 format which is the latest SBML version and supports hierarchical models.

WebTarget target = VPRWebServiceClient.getVPRWebServiceTarget(VPR_WS);
SBMLDocument sbmlDoc = VPRWebServiceClient.getModel(target, sbolDesign);

Disconnected mode

Using the library in connected mode

This option allows users to specify basic information about about genetic circuit design and retrive an SBML model using the information from a remote data repository, which may be the default VPR repository or another SBOL enabled repository such as a SynBioHub instance.

The following code creates an SBML model using an SBOL design as a parameter. An additional parameter is also used to specify the URI of the SPARQL interface of the remote repository.

WebTarget target=VPRWebServiceClient.getVPRWebServiceTarget(VPR_WS);
SBOLDocument sbolDesign=SVPWriteHandler.convertToSBOL(design,"tu");    	    	    	
SBMLDocument sbmlDoc=VPRWebServiceClient.getModelUsingDataFromStack(target, sbolDesign, VPR_Repository);

Connected mode

Creating SBOL designs

VPR2’s client library is ideal to create SBOL designs and to retrieve SBML models (see “Using the VPR2 Web Service Client”). This library provides both the syntax and the semantics when creating SBOL designs. Please note that that the libSBOLj java library is already included as part of the VPR2 client library. Alternatively, simple designs can be constructed via the SVPWrite language using the following notation. Note that each part id-type pair MUST be separated by a semicolon. The LAST pair MUST NOT be followed by a semicolon.

<partid>:<parttype>

Part types in SVPWrite are:

The following example creates the prom1-rbs1-cds1-ter1 design where prom1 is a promoter, rbs1 is an RBS, cds1 is a CDS and ter1 is a terminator.

String design="prom1:prom;rbs1:rbs;cds1:cds;ter1:ter";
SBOLDocument sbolDesign=SVPWriteHandler.convertToSBOL(design,"tu");

SBOL equivalents of newly created design components can be referred to directly from the SBOL documents as shown below. The cds1 component is retrieved back as an SBOL ComponentDefinition object, which can then be used to define interactions.

ComponentDefinition cdsCompDef=sbolDesign.getComponentDefinition(URI.create(sbolDesign.getDefaultURIprefix() + "cds1"));

Adding information about biological interactions

In order to create interactions in the disconnected mode, interactions must be fully specified. Interactions MUST be created using the interaction types presented in https://pubs.acs.org/doi/abs/10.1021/acssynbio.7b00459. The VPR provides SBOLInteraction class to guarantee that the interactions are created correctly. Interactions must be created as part of a single SBOL ModuleDefinition which is the container entity for biological interactions. The VPR library supports the following interactions.

The example below creates a ModuleDefinion as a container store information about interactions. Next, it creates two interactions. The first interaction represents the translation of the LacI protein from the lacI coding sequence. The second interaction represents the repression of the pTac promoter by the LacI protein.

ModuleDefinition moduleDef=sbolDesign.createModuleDefinition("design_module");
SBOLInteraction.createTranslationInteraction(moduleDef, lacI, LacI);
SBOLInteraction.createPromoterRepression(moduleDef, pTac, LacI);

Controlling kinetic rate parameters

The VPR library populates SBML models with default values. These values can also be controlled by the user. Often, parameters are properties of interaction objects. For example, the following code creates a repression interaction. The forward rate of this interaction can be overwritten by the user. In the example, the new value is set to 0.1.

Interaction repression=SBOLInteraction.createPromoterRepression(moduleDef, pTac, LacI);
repression.createAnnotation(VPRTerms.toQName(VPRTerms.parameter.kforward,VPRTerms.Ns.getPrefix()), "0.1");

Saving models

The VPR returns an object representing the model using rhe jSBML library. This model can directly be written to a file.

SBMLWriter.write(sbmlDoc, "repressibleTU_Disconnected.xml",' ', (short) 2);

Creating SBOL designs using external tools

SBOL designs can also be created using different SBOL tools and libraries in order to use the VPR2 web service via HTTP directly. VPR2 requires that such SBOL designs provide the necessary semantics about the types, and roles, of biological components and molecular interactions.

Part SBOL Component type SBOL Component Role
Promoter http://www.biopax.org/release/biopax-level3.owl#DnaRegion http://identifiers.org/so/SO:0000167
CDS http://www.biopax.org/release/biopax-level3.owl#DnaRegion http://identifiers.org/so/SO:0000316
RBS http://www.biopax.org/release/biopax-level3.owl#DnaRegion http://identifiers.org/so/SO:0000139
Terminator http://www.biopax.org/release/biopax-level3.owl#DnaRegion http://identifiers.org/so/SO:0000141
Operator http://www.biopax.org/release/biopax-level3.owl#DnaRegion http://identifiers.org/so/SO:0000057
Shim/Spacer http://www.biopax.org/release/biopax-level3.owl#DnaRegion http://identifiers.org/so/SO:0000804
Protein http://www.biopax.org/release/biopax-level3.owl#Protein  

Interaction types should be set as below. In addition, each interaction includes a list of participants and how their roles should be set.

Examples

Below you can find complete examples, using the Java web service client API or using the web service directly via the command line CURL tool. As a result of each exmaple, an SBML model is generated. This model can be simulated using the COPASI tool.

Example files are available from the wikiexamples folder.

Ex1: A simple genetic production - disconnected

This example shows how to create a simple genetic circuit that encodes for a protein.

Ex1: Using the VPR2-WS Client API

String design="prom1:prom;rbs1:rbs;cds1:cds;ter1:ter"; 
WebTarget target=VPRWebServiceClient.getVPRWebServiceTarget(VPR_WS);
SBMLDocument sbmlDoc=VPRWebServiceClient.getModel(target, design);
SBMLWriter.write(sbmlDoc, "repressibleTU_DisconnectedSimple.xml",' ', (short) 2);  

Ex1: Using the Curl command line tool and the VPR2-WS

repressibleTU_DisconnectedSimple.svp file:

prom1:prom;rbs1:rbs;cds1:cds;ter1:ter

Specify a genetic circuit as a curl parameter:

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/svpwrite" --data-urlencode 'svpwrite=prom1:prom;rbs1:rbs;cds1:cds;ter1:ter' -d 'modeltype=sbml_l3' -d 'abstractionlevel=simple'

Specify a genetic circuit as a curl parameter that refers to the input SVPWrite file:

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/svpwrite" --data-urlencode svpwrite@repressibleTU_DisconnectedSimple.svp -d 'modeltype=sbml_l3' -d 'abstractionlevel=simple'

Specify a genetic circuit as a curl parameter that refers to the input SVPWrite file. The output will be written to an SBML file.

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/svpwrite" --data-urlencode svpwrite@repressibleTU_DisconnectedSimple.svp -d 'modeltype=sbml_l3' -d 'abstractionlevel=simple' > repressibleTU_DisconnectedSimple.xml

Curl command with the parameters explained:

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/svpwrite"	--> The VPR web interface to use the SVPWrite strings
		--data-urlencode svpwrite@repressibleTU_DisconnectedSimple.svp	-->svpwrite parameters include the local file name containing the design
		-d 'modeltype=sbml_l3'	--> Model type is SBML L3
		-d 'abstractionlevel=simple'	--> The VPR2 modelling abstraction is specified 
	> repressibleTU_DisconnectedSimple.xml	--> Write the SBML output to repressibleTU_DisconnectedSimple.xml

Ex2: Incorporating constraints between parts - disconnected

This example builds upon the previous one by adding with molecular interactions.

Ex2: Adding molecular interactions and retrieving the corresponding model using the VPR2-WS Client API

String design="prom1:prom;rbs1:rbs;cds1:cds;ter1:ter";
SBOLDocument sbolDesign=SVPWriteHandler.convertToSBOL(design,"tu");
     
ComponentDefinition tf=sbolDesign.createComponentDefinition("tf", ComponentDefinition.PROTEIN);
ComponentDefinition prom=sbolDesign.getComponentDefinition(getURI(sbolDesign, "prom1"));
ComponentDefinition cds=sbolDesign.getComponentDefinition(getURI(sbolDesign, "cds1"));     
         
ModuleDefinition moduleDef=sbolDesign.createModuleDefinition("design_module");
SBOLInteraction.createPromoterRepression(moduleDef,prom, tf);
SBOLInteraction.createTranslationInteraction(moduleDef, cds, tf);

WebTarget target=VPRWebServiceClient.getVPRWebServiceTarget(VPR_WS);
SBMLDocument sbmlDoc=VPRWebServiceClient.getModel(target, sbolDesign);
     
SBOLWriter.write(sbolDesign, "repressibleTU_Disconnected.rdf");
SBMLWriter.write(sbmlDoc, "repressibleTU_Disconnected.xml",' ', (short) 2);

Ex2: Using the Curl command line tool and the VPR2-WS

It is assumed that the SBOL file including the description of the circuit and related molecular interactions exists.

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/sbol" --data-urlencode sbol@repressibleTU_Disconnected.rdf -d 'modeltype=sbml_l3' -d 'abstractionlevel=simple' > repressibleTU_Disconnected.xml

The same command in multiple lines:

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/sbol" \
		--data-urlencode sbol@repressibleTU_Disconnected.rdf \
		-d 'modeltype=sbml_l3' \
		-d 'abstractionlevel=simple' \
	> repressibleTU_Disconnected.xml

Ex3: Using a specified constraints repository - connected (A negative autoregulatory circuit)

In this example, a SynBioHub instance instance with parts and corresponding interaction data is used. The genetic circuit consists of a promoter, an RBS and a CDS. The CDS encodes for a TF, which inhibits the promoter.

Ex3: Retrieving the model using a specified remote repository - via the VPR2-WS Client API

Specifyihg the types and order of parts to r

String svpDesign="BO_2685:prom;BO_27783:rbs;BO_32077:cds;BO_4257:ter";
svpDesign=getSVPDesign("https://synbiohub.org/public/bsu/%s/1",svpDesign);
WebTarget target=VPRWebServiceClient.getVPRWebServiceTarget(VPR_WS);
SBOLDocument sbolDesign=SVPWriteHandler.convertToSBOL(svpDesign,"tu");             
SBMLDocument sbmlDoc=VPRWebServiceClient.getModelUsingDataFromStack(target, sbolDesign, "https://synbiohub.org/sparql");

The content of the svpDesign variable. Each part is defined using its URI from the SynBioHub repository.

<https://synbiohub.org/public/bsu/BO_2685/1>:prom;<https://synbiohub.org/public/bsu/BO_27783/1>:rbs;<https://synbiohub.org/public/bsu/BO_32077/1>:cds;<https://synbiohub.org/public/bsu/BO_4257/1>:ter

Ex3: Using the Curl command line tool and the VPR2-WS (Input data is SBOL)

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/sbol_fromstack" --data-urlencode sbol@repressibleTU_Connected.rdf -d 'modeltype=sbml_l3' -d 'abstractionlevel=simple' -d 'stackuri=https://synbiohub.org/sparql' > repressibleTU_Connected.xml

The same command in multiple lines:

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/sbol_fromstack" \
		--data-urlencode sbol@repressibleTU_Connected.rdf \
		-d 'modeltype=sbml_l3' \
		-d 'abstractionlevel=simple' \
		-d 'stackuri=https://synbiohub.org/sparql' \
	> repressibleTU_Connected.xml

Ex3: Using the Curl command line tool and the VPR2-WS (Input data is SVPWrite)

repressibleTU_Connected.svp:

<https://synbiohub.org/public/bsu/BO_2685/1>:prom;<https://synbiohub.org/public/bsu/BO_27783/1>:rbs;<https://synbiohub.org/public/bsu/BO_32077/1>:cds;<https://synbiohub.org/public/bsu/BO_4257/1>:ter

Curl command:

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/svpwrite_fromstack" --data-urlencode svpwrite@repressibleTU_Connected.svp -d 'modeltype=sbml_l3' -d 'abstractionlevel=simple' -d 'stackuri=https://synbiohub.org/sparql' > repressibleTU_ConnectedSVP.xml

The same command in multiple lines:

curl -X POST "http://virtualparts.org/virtualparts-ws/webapi/model/svpwrite_fromstack" \
		--data-urlencode svpwrite@repressibleTU_Connected.svp \
		-d 'modeltype=sbml_l3' \
		-d 'abstractionlevel=simple' \
		-d 'stackuri=https://synbiohub.org/sparql' \
	> repressibleTU_Connected.xml