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Goals

This page describes the process of creating an example pathway that includes BioPAX information. By creating this pathway I hope to get an idea about the best way how to include BioPAX, what to include and what not, and identify problems with the current approach. I'm going to create a GPML/BioPAX version of the Notch Signalling pathway, starting from Reactome and maybe including NetPath? information later on. My goal is to include as much information as possible while keeping the visual representation in PathVisio as clear and intuitive as possible. An example of what I DONT want to create is the  NetPath Delta-Notch pathway, that visualizes all possible interactions. I would like to restrict to drawing the main signaling process and key regulators. Underneath that drawing will be a more complete representation stored in BioPAX.

The reactome Notch Signalling pathway

The  Reactome Notch Signalling pathway describes the lifecycle of the Notch receptor from translation to regulation of it's downstream genes. It does not include interactions that regulate this process. The steps in the pathway are:

  • Transport of Notch receptor precursor to golgi
  • Maturation of Notch precursor via proteolytic cleavage
  • Mature Notch receptor trafficks to plasma membrane
  • Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor
  • A third proteolytic cleavage releases NICD
  • NICD trafficks to nucleus

Drawing the Reactome pathway in PathVisio

Here is the Reactome pathway as drawn in PathVisio: As you see this simple pathway is getting quite crowded already, but we assume that the boxed elements are grouped and can be collapsed (see [variants]).

Note that the 'Notch EC', 'Notch TM', 'Notch NEXT' and NICD have the same Uniprot ID (see [of cleaved fragments|Annotation of cleaved fragments]).

Protein variants

By trying to draw each step in GPML the first problem that I stumbled upon was that each step 4 versions, because the Notch receptor has 4 variants (not sure if this is the right biological term, may also be iso-forms? But let's call them variants for now). Because the steps are all the same (which may be not the case in biology, but this is probably all we know), it doesn't make sense to create 4 separate pathways. But we also can't just take one variant, because if we are going to map data on it, we want to see all of them. I looked in to the classic GenMAPP pathways, and there it's solved to stack all 4 proteins, just like with complexes. So the logical solution in GPML would be to group them and create a new group type 'Variants' (or the correct biological term). This way we can distinct them from complexes, and prevent the pathway to become big by collapsing them into a single Notch gene box by default.

The drawing above assumes that we can group the protein variants and collapse them (so it won't look so messy when we implement this in PathVisio). The blue boxes contain the 'Variants' groups, that can be collapsed into a smaller box. Maybe we should give the Group element a 'label' attribute, so that we can show a single label on the collapsed form. This could be useful for both the complex and variants style.

Proposed solution: add a special group type for protein variants

The Gamma secretase complex

So, let's add some BioPAX then. A good point to start is the Gamma-secretase complex:

This complex contains a sub-complex and protein variants, so it is also a good example to illustrate the Group element in GPML. The complex is built of 4 different proteins. One protein (presenilin) participates in the complex as a homo-dimer. Two proteins (presenilin and NCSTN) have variants that can all be part of the complex (if I understand reactome correctly, they don't participate all at once, but either one of the variants). Here is a GPML snippet of the image above, that contains the groups (I left the boxes and labels out): 

<?xml version="1.0" encoding="ISO-8859-1"?>

<Pathway  xmlns="http://genmapp.org/GPML/2007" Name="Gamma-secretase complex example" Data-Source="GenMAPP 2.0" Version="20070427"> 
	<Graphics BoardWidth="18000.0" BoardHeight="12000.0" WindowWidth="18000.0" WindowHeight="12000.0" />

	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="ec4" groupRef="f1e">

		<Graphics Color="Transparent" CenterX="1950.0" CenterY="4965.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768" />

	</DataNode>
	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="e8e" groupRef="f1e">

		<Graphics Color="Transparent" CenterX="2805.0" CenterY="4965.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768-2" />

	</DataNode>

	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="c1b" groupRef="f1e">

		<Graphics Color="Transparent" CenterX="3660.0" CenterY="4965.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768-3" />

	</DataNode>

	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="a45" groupRef="f1e">

		<Graphics Color="Transparent" CenterX="4515.0" CenterY="4965.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768-4" />

	</DataNode>

	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="bc9" groupRef="f1e">

		<Xref Database="SwissProt" ID="P49768-5" />

	</DataNode>

	<DataNode TextLabel="PSEN2" Type="Unknown" GraphId="d29" groupRef="f1e">

		<Graphics Color="Transparent" CenterX="6195.0" CenterY="4965.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49810" />

	</DataNode>

	<DataNode TextLabel="PSEN2" Type="Unknown" GraphId="c8b" groupRef="f1e">

		<Graphics Color="Transparent" CenterX="7050.0" CenterY="4965.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49810-2" />

	</DataNode>
	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="dbd" groupRef="f2e">
		<Graphics Color="Transparent" CenterX="1995.0" CenterY="5865.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768" />

	</DataNode>
	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="c64" groupRef="f2e">

		<Graphics Color="Transparent" CenterX="2850.0" CenterY="5865.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768-2" />

	</DataNode>
	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="df7" groupRef="f2e">

		<Graphics Color="Transparent" CenterX="3705.0" CenterY="5865.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768-3" />

	</DataNode>

	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="eba" groupRef="f2e">

		<Graphics Color="Transparent" CenterX="4560.0" CenterY="5865.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768-4" />

	</DataNode>
	<DataNode TextLabel="PSEN1" Type="Unknown" GraphId="a31" groupRef="f2e">

		<Graphics Color="Transparent" CenterX="5400.0" CenterY="5865.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49768-5" />

	</DataNode>

	<DataNode TextLabel="PSEN2" Type="Unknown" GraphId="c4d" groupRef="f2e">

		<Graphics Color="Transparent" CenterX="6240.0" CenterY="5865.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49810" />

	</DataNode>

	<DataNode TextLabel="PSEN2" Type="Unknown" GraphId="c9b" groupRef="f2e">

		<Graphics Color="Transparent" CenterX="7095.0" CenterY="5865.0" Width="810.0" Height="300.0" />

		<Xref Database="SwissProt" ID="P49810-2" />

	</DataNode>

	<DataNode TextLabel="NCSTN" Type="Unknown" GraphId="e55" groupRef="f4e">

		<Graphics Color="Transparent" CenterX="3285.0" CenterY="2745.0" Width="1200.0" Height="300.0" />

		<Xref Database="SwissProt" ID="Q92542-2" />

	</DataNode>
	<DataNode TextLabel="NCSTN" Type="Unknown" GraphId="b2f" groupRef="f4e">

		<Graphics Color="Transparent" CenterX="2025.0" CenterY="2745.0" Width="1200.0" Height="300.0" />

		<Xref Database="SwissProt" ID="Q92542" />

	</DataNode>

	<DataNode TextLabel="APH1B" Type="Unknown" GraphId="c95" groupRef="f5e">

		<Graphics Color="Transparent" CenterX="1890.0" CenterY="3405.0" Width="1380.0" Height="300.0" />

		<Xref Database="SwissProt" ID="Q8WW43" />

	</DataNode>
	<DataNode TextLabel="PSENEN" Type="Unknown" GraphId="f98" groupRef="f5e">

		<Graphics Color="Transparent" CenterX="1920.0" CenterY="1770.0" Width="1380.0" Height="300.0" />

		<Xref Database="SwissProt" ID="Q9NZ42" />

	</DataNode>
	<Group groupId="f1e" Style="Variants" groupRef="f3e"/>
	<Group groupId="f2e" Style="Variants" groupRef="f3e"/>
	<Group groupId="f3e" Style="Complex" groupRef="f5e"/>
	<Group groupId="f4e" Style="Variants" groupRef="f5e"/>
	<Group groupId="f5e" Style="Complex"/>

	<InfoBox CenterX="0.0" CenterY="0.0" />

</Pathway>

Note that we have nested groups here, the two variants and a sub-complex (the presenilin homo-dimer).

Now we can add BioPAX information to the DataNodes? and Groups. Beware that we don't want to add redundant information that is already in the GPML file, so we don't want to add:

  • For DataNodes? (corresponding BioPAX element will depend on type, e.g. bp:protein for 'Protein'): ** bp:XREF to genes or proteins in a database (we can derive this from GPML's XRef)
  • For Groups (corresponding BioPAX element will depend on type, e.g. bp:complex for 'Complex') ** bp:sequenceParticipant (we can derive this from the referring DataNodes?)
  • bp:ORGANISM (can be derived from the pathway's organism

But do want to add:

  • Synonyms
  • Cellular location
  • Literature/evidence
  • Interaction/reaction information
  • [...]

By adding the non-redundant information from Reactome, we get something like this (I removed all elements without BioPAX information, they are identical to the snippet above): 

<?xml version="1.0" encoding="ISO-8859-1"?>

<Pathway  xmlns="http://genmapp.org/GPML/2007" xmlns:bp="http://www.biopax.org/release/biopax-level2.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:rdfs="http://www.w3.org/2000/01/rdf-schema#" xmlns:owl="http://www.w3.org/2002/07/owl#" Name="Gamma-secretase complex example" Data-Source="GenMAPP 2.0" Version="20070427">

	<Biopax>
		<bp:dataSource rdf:ID="ReactomeDataSource">

			<bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:NAME>

			<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">http://www.reactome.org</bp:COMMENT>

		</bp:dataSource>
		<bp:openControlledVocabulary rdf:ID="plasma_membrane">

			<bp:TERM rdf:datatype="http://www.w3.org/2001/XMLSchema#string">plasma membrane</bp:TERM>

			<bp:XREF rdf:resource="#GO_0005886" />

		</bp:openControlledVocabulary>
		<bp:unificationXref rdf:ID="GO_0005886">

			<bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">GO</bp:DB>

			<bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">0005886</bp:ID>

		</bp:unificationXref>
	</Biopax>  
	
<...>

	<DataNode TextLabel="APH1B" Type="Unknown" GraphId="c95" groupRef="f5e">
		<Biopax>
			<bp:protein rdf:ID="APH_1__plasma_membrane_1">

				<bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

				<bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">APH-1 [plasma membrane]</bp:NAME>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Converted from EventSet in Reactome. Each synonym is a name of a ConcreteEntity, and each XREF points to one ConcreteEntity</bp:COMMENT>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">APH-1B [plasma membrane]</bp:SYNONYMS>

			</bp:protein>
		</Biopax>

		<Graphics Color="Transparent" CenterX="1890.0" CenterY="3405.0" Width="1380.0" Height="300.0" />

		<Xref Database="SwissProt" ID="Q8WW43" />

	</DataNode>
	<DataNode TextLabel="PSENEN" Type="Unknown" GraphId="f98" groupRef="f5e">
		<Biopax>
			<bp:protein rdf:ID="UniProt_Q9NZ42_Gamma_secretase_subunit_PEN_2__Presenilin_enhancer_protein_2___MDS033_">

				<bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

				<bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">UniProt:Q9NZ42 Gamma-secretase subunit PEN-2 (Presenilin enhancer protein 2) (MDS033)</bp:NAME>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PEN2</bp:SYNONYMS>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">FUNCTION: Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta- amyloid precursor protein). Probably represents the last step of maturation of gamma-secretase, facilitating endoproteolysis of presenilin and confering gamma-secretase activity. SUBUNIT: Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist. SUBCELLULAR LOCATION: Integral membrane protein (Potential). Predominantly located in the endoplasmic reticulum and in the cis- Golgi. TISSUE SPECIFICITY: Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain. SIMILARITY: Belongs to the PEN-2 family.</bp:COMMENT>

			</bp:protein>
		</Biopax>

		<Graphics Color="Transparent" CenterX="1920.0" CenterY="1770.0" Width="1380.0" Height="300.0" />

		<Xref Database="SwissProt" ID="Q9NZ42" />

	</DataNode>
	<Group groupId="f1e" Style="Variants" groupRef="f3e">
		<Biopax>
			<bp:protein rdf:ID="Presenilin__plasma_membrane_1">

				<bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

				<bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin [plasma membrane]</bp:NAME>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Converted from EventSet in Reactome. Each synonym is a name of a ConcreteEntity, and each XREF points to one ConcreteEntity</bp:COMMENT>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 5) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin2 (variant 2) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin2 (variant 1) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 1) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 2) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 3) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 4) [plasma membrane]</bp:SYNONYMS>

			</bp:protein>
			<bp:unificationXref rdf:ID="REACT_4710.1">

				<bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

				<bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">REACT_4710</bp:ID>

				<bp:ID-VERSION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">1</bp:ID-VERSION>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4710.1</bp:COMMENT>

			</bp:unificationXref>
		</Biopax>
	</Group>
	<Group groupId="f2e" Style="Variants" groupRef="f3e">
		<Biopax>
			<bp:protein rdf:ID="Presenilin__plasma_membrane_1">

				<bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

				<bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin [plasma membrane]</bp:NAME>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Converted from EventSet in Reactome. Each synonym is a name of a ConcreteEntity, and each XREF points to one ConcreteEntity</bp:COMMENT>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 5) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin2 (variant 2) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin2 (variant 1) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 1) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 2) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 3) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin1 (variant 4) [plasma membrane]</bp:SYNONYMS>

			</bp:protein>
			<bp:unificationXref rdf:ID="REACT_4710.1">

				<bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

				<bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">REACT_4710</bp:ID>

				<bp:ID-VERSION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">1</bp:ID-VERSION>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4710.1</bp:COMMENT>

			</bp:unificationXref>
		</Biopax>
	</Group>
	<Group groupId="f3e" Style="Complex" groupRef="f5e">
		<Biopax>
			<bp:complex rdf:ID="Presenilin_homodimer__plasma_membrane_1">

				<bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin homodimer [plasma membrane]</bp:NAME>

				<bp:SHORT-NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Presenilin homodimer</bp:SHORT-NAME>

				<bp:XREF rdf:resource="#Reactome157352" />

				<bp:XREF rdf:resource="#REACT_4710.1" />

				<bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

			</bp:complex>
			<bp:unificationXref rdf:ID="Reactome157352">

				<bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

				<bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">157352</bp:ID>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&amp;ID=157352</bp:COMMENT>

			</bp:unificationXref>
		</Biopax>
	</Group>
	<Group groupId="f4e" Style="Variants" groupRef="f5e">
		<Biopax>
			<bp:protein rdf:ID="Nicastrin__plasma_membrane_1">

				<bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

				<bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Nicastrin [plasma membrane]</bp:NAME>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Converted from EventSet in Reactome. Each synonym is a name of a ConcreteEntity, and each XREF points to one ConcreteEntity</bp:COMMENT>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Nicastrin (variant 1) [plasma membrane]</bp:SYNONYMS>

				<bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Nicastrin (variant 2) [plasma membrane]</bp:SYNONYMS>

			</bp:protein>
		</Biopax>
	</Group>
	<Group groupId="f5e" Style="Complex">
		<Biopax>
			<bp:complex rdf:ID="gamma_secretase_complex__plasma_membrane_1">

				<bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">gamma-secretase complex [plasma membrane]</bp:NAME>

				<bp:SHORT-NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">gamma-secretase complex</bp:SHORT-NAME>

				<bp:XREF rdf:resource="#Reactome157343" />

				<bp:XREF rdf:resource="#REACT_5292.1" />

				<bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

			</bp:complex>
			<bp:unificationXref rdf:ID="REACT_5292.1">

				<bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

				<bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">REACT_5292</bp:ID>

				<bp:ID-VERSION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">1</bp:ID-VERSION>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5292.1</bp:COMMENT>

			</bp:unificationXref>
			<bp:unificationXref rdf:ID="Reactome157343">

				<bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

				<bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">157343</bp:ID>

				<bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&amp;ID=157343</bp:COMMENT>

			</bp:unificationXref>
		</Biopax>
	</Group>

	<InfoBox CenterX="0.0" CenterY="0.0" />

</Pathway>

Note: All names and identifiers are kept the same as in the Reactome owl.

If we now extract the text from the BioPAX elements and put them in an owl file, it  validates! This is somewhat unexpected, because you would think that e.g. an element of type bp:complex must have a COMPONENTS property (which we left out here, because we can derive it from GPML).

Adding BioPAX for pathway steps

The Reactome pathway also information for each pathway step (interaction, reaction, transport) Each pathway step in the pathway drawing is represented as two groups, connected by an arrow, and a genebox/group that performs the reaction. Let's take the 2nd step as example. To make it simple, we assume that there's only one Notch variant: [[Image:(NotchStep.png)]]

In the GPML file this is represented as: 

<?xml version="1.0" encoding="ISO-8859-1"?>

<Pathway xmlns="http://genmapp.org/GPML/2007" Name="Maturation of Notch precursor" Data-Source="GenMAPP 2.0" Version="20070430">

    <Graphics BoardWidth="8000.0" BoardHeight="5000.0" WindowWidth="18000.0" WindowHeight="12000.0" />

    <DataNode TextLabel="Furin" Type="Unknown" GraphId="e0a">

        <Graphics Color="Transparent" CenterX="3990.0" CenterY="1620.0" Width="1200.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 polypeptide" Type="Unknown" GraphId="feb">

        <Graphics Color="Transparent" CenterX="2160.0" CenterY="1845.0" Width="1950.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 EC" Type="Unknown" GraphId="cc2" GroupRef="ef1">

        <Graphics Color="Transparent" CenterX="5655.0" CenterY="1860.0" Width="1050.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 TM" Type="Unknown" GraphId="a04" GroupRef="ef1">

        <Graphics Color="Transparent" CenterX="6750.0" CenterY="1860.0" Width="1050.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <Line>

        <Graphics Color="Transparent">

            <Point x="3315.0" y="1875.0" Head="Arrow" GraphRef="feb" />

            <Point x="5055.0" y="1875.0" GraphRef="cd5" />

        </Graphics>

    </Line>
    <Group GraphId="cd5" GroupId="ef1" Type="Complex" />

    <InfoBox CenterX="0.0" CenterY="0.0" />

</Pathway>

Now let's add the BioPAX information: 

<?xml version="1.0" encoding="ISO-8859-1"?>

<Pathway xmlns="http://genmapp.org/GPML/2007" Name="Maturation of Notch precursor" Data-Source="GenMAPP 2.0" Version="20070430">

    <Graphics BoardWidth="8000.0" BoardHeight="5000.0" WindowWidth="18000.0" WindowHeight="12000.0" />

    <DataNode TextLabel="Furin" Type="Unknown" GraphId="e0a">
		<Biopax>
		  <bp:protein rdf:ID="UniProt_P09958_Furin_precursor__EC_3_4_21_75___Paired_basic_amino_acid_residue_cleaving_enzyme___PACE___Dibasic_processing_enzyme_">

		    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		    <bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">UniProt:P09958 Furin precursor (EC 3.4.21.75) (Paired basic amino acid residue cleaving enzyme) (PACE) (Dibasic processing enzyme)</bp:NAME>

		    <bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PACE</bp:SYNONYMS>

		    <bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">FUR</bp:SYNONYMS>

		    <bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">FURIN</bp:SYNONYMS>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">FUNCTION: Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif. CATALYTIC ACTIVITY: Release of mature proteins from their proproteins by cleavage of Arg-Xaa-Yaa-Arg-|-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and von Willebrand factor from their respective precursors. COFACTOR: Calcium. ENZYME REGULATION: Could be inhibited by the not secondly cleaved propeptide. SUBUNIT: Interacts with FLNA (By similarity). Binds to PACS1 which mediates TGN localization and connection to clathrin adapters. SUBCELLULAR LOCATION: Seems to be localized intracellularly to the trans Golgi network. Propeptide cleavage is a prerequisite for exit of furin molecules out of the endoplasmic reticulum (ER). Second cleavage in the propeptide occur in the trans Golgi network (TGN), which is followed by the release of the propeptide bound to furin and the activation of furin. TISSUE SPECIFICITY: Seems to be expressed ubiquitously. DOMAIN: Contains a cytoplasmic domain responsible for its TGN localization and recycling from the cell surface. PTM: The propeptide is autocatalytically removed through an intramolecular cleavage probably in the endoplasmic reticulum (ER). In the TGN the second cleavage in the propeptide could lead to the activation of furin. PTM: Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms. SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily. SIMILARITY: Contains 1 homo B/P domain.</bp:COMMENT>

		  </bp:protein>
		</Biopax>

        <Graphics Color="Transparent" CenterX="3990.0" CenterY="1620.0" Width="1200.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 polypeptide" Type="Unknown" GraphId="feb">

        <Graphics Color="Transparent" CenterX="2160.0" CenterY="1845.0" Width="1950.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 EC" Type="Unknown" GraphId="cc2" GroupRef="ef1">
		<Biopax>
		  <bp:sequenceParticipant rdf:ID="Notch_1_Extracellular_fragment__NEC___Golgi_lumen_">

		    <bp:CELLULAR-LOCATION rdf:resource="#Golgi_lumen" />

		    <bp:PHYSICAL-ENTITY rdf:resource="#UniProt_P46531_Neurogenic_locus_notch_homolog_protein_1_precursor__Notch_1___hN1___Translocation_associated_notch_protein_TAN_1_" />

		    <bp:SEQUENCE-FEATURE-LIST rdf:resource="#Length_19__1_" />

		    <bp:STOICHIOMETRIC-COEFFICIENT rdf:datatype="http://www.w3.org/2001/XMLSchema#double">1</bp:STOICHIOMETRIC-COEFFICIENT>

		  </bp:sequenceParticipant>

		  <bp:sequenceFeature rdf:ID="Length_19__1_">

		    <bp:FEATURE-TYPE rdf:resource="#LengthFeature" />

		    <bp:FEATURE-LOCATION rdf:resource="#SequenceInterval1" />

		  </bp:sequenceFeature>

		  <bp:sequenceInterval rdf:ID="SequenceInterval1">

		    <bp:SEQUENCE-INTERVAL-BEGIN rdf:resource="#SequenceSite2" />

		    <bp:SEQUENCE-INTERVAL-END rdf:resource="#SequenceSite3" />

		  </bp:sequenceInterval>

		  <bp:sequenceSite rdf:ID="SequenceSite2">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">19</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		  </bp:sequenceSite>

		  <bp:sequenceSite rdf:ID="SequenceSite3">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">-1</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		  </bp:sequenceSite>
		</Biopax>

        <Graphics Color="Transparent" CenterX="5655.0" CenterY="1860.0" Width="1050.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 TM" Type="Unknown" GraphId="a04" GroupRef="ef1">
		<Biopax>
		   <bp:sequenceParticipant rdf:ID="Notch_1_Transmembrane_fragment__NTM___Golgi_lumen_">

		    <bp:CELLULAR-LOCATION rdf:resource="#Golgi_lumen" />

		    <bp:PHYSICAL-ENTITY rdf:resource="#UniProt_P46531_Neurogenic_locus_notch_homolog_protein_1_precursor__Notch_1___hN1___Translocation_associated_notch_protein_TAN_1_" />

		    <bp:SEQUENCE-FEATURE-LIST rdf:resource="#Length_1_2556_" />

		    <bp:STOICHIOMETRIC-COEFFICIENT rdf:datatype="http://www.w3.org/2001/XMLSchema#double">1</bp:STOICHIOMETRIC-COEFFICIENT>

		  </bp:sequenceParticipant>

		  <bp:sequenceFeature rdf:ID="Length_1_2556_">

		    <bp:FEATURE-TYPE rdf:resource="#LengthFeature" />

		    <bp:FEATURE-LOCATION rdf:resource="#SequenceInterval" />

		  </bp:sequenceFeature>

		  <bp:openControlledVocabulary rdf:ID="LengthFeature">

		    <bp:TERM rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Chain Coordinates</bp:TERM>

		  </bp:openControlledVocabulary>

		  <bp:sequenceInterval rdf:ID="SequenceInterval">

		    <bp:SEQUENCE-INTERVAL-BEGIN rdf:resource="#SequenceSite" />

		    <bp:SEQUENCE-INTERVAL-END rdf:resource="#SequenceSite1" />

		  </bp:sequenceInterval>

		  <bp:sequenceSite rdf:ID="SequenceSite">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">1</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		  </bp:sequenceSite>

		  <bp:sequenceSite rdf:ID="SequenceSite1">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">2556</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		  </bp:sequenceSite>
		</Biopax>

        <Graphics Color="Transparent" CenterX="6750.0" CenterY="1860.0" Width="1050.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <Line>
	<Biopax>  
		<bp:pathwayStep rdf:ID="Notch_1_precursor_cleaved_to_form_a_heterodimerStep">

    		<bp:STEP-INTERACTIONS rdf:resource="#Notch_1_precursor_cleaved_to_form_a_heterodimer" />

    		<bp:NEXT-STEP rdf:resource="#Notch_1_heterodimer_trafficks_to_the_plasma_membraneStep" />

    		<bp:STEP-INTERACTIONS rdf:resource="#furin_activity_of_furin__Golgi_membrane_" />

  		</bp:pathwayStep>
		<bp:biochemicalReaction rdf:ID="Notch_1_precursor_cleaved_to_form_a_heterodimer">

		    <bp:LEFT rdf:resource="#Notch_1_receptor_precursor__Golgi_lumen_1" />

		    <bp:RIGHT rdf:resource="#NTM_NEC_1_heterodimer__Golgi_lumen_" />

		    <bp:EC-NUMBER rdf:datatype="http://www.w3.org/2001/XMLSchema#string">3.4.21.75</bp:EC-NUMBER>

		    <bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Notch 1 precursor cleaved to form a heterodimer</bp:NAME>

		    <bp:SHORT-NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Notch 1 precursor cleaved to form a heterodimer</bp:SHORT-NAME>

		    <bp:XREF rdf:resource="#Reactome157042" />

		    <bp:XREF rdf:resource="#REACT_1127.2" />

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">At the beginning of this reaction, 1 molecule of 'Notch 1 receptor precursor' is present. At the end of this reaction, 1 molecule of 'NTM-NEC 1 heterodimer' is present.&lt;br&gt;&lt;br&gt; This reaction takes place in the 'Golgi lumen' and  is mediated by the 'furin activity' of 'furin'.&lt;br&gt;</bp:COMMENT>

		    <bp:XREF rdf:resource="#Pubmed_9653148" />

		    <bp:XREF rdf:resource="#Pubmed_9244302" />

		    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		  </bp:biochemicalReaction>

		  <bp:sequenceParticipant rdf:ID="Notch_1_receptor_precursor__Golgi_lumen_1">

		    <bp:CELLULAR-LOCATION rdf:resource="#Golgi_lumen" />

		    <bp:PHYSICAL-ENTITY rdf:resource="#UniProt_P46531_Neurogenic_locus_notch_homolog_protein_1_precursor__Notch_1___hN1___Translocation_associated_notch_protein_TAN_1_" />

		    <bp:STOICHIOMETRIC-COEFFICIENT rdf:datatype="http://www.w3.org/2001/XMLSchema#double">1</bp:STOICHIOMETRIC-COEFFICIENT>

		  </bp:sequenceParticipant>

		  <bp:physicalEntityParticipant rdf:ID="NTM_NEC_1_heterodimer__Golgi_lumen_">

		    <bp:CELLULAR-LOCATION rdf:resource="#Golgi_lumen" />

		    <bp:PHYSICAL-ENTITY rdf:resource="#NTM_NEC_1_heterodimer__Golgi_lumen_1" />

		    <bp:STOICHIOMETRIC-COEFFICIENT rdf:datatype="http://www.w3.org/2001/XMLSchema#double">1</bp:STOICHIOMETRIC-COEFFICIENT>

		  </bp:physicalEntityParticipant>

		  <bp:unificationXref rdf:ID="Reactome157091">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">157091</bp:ID>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&amp;ID=157091</bp:COMMENT>

		  </bp:unificationXref>

		  <bp:unificationXref rdf:ID="REACT_5481.1">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">REACT_5481</bp:ID>

		    <bp:ID-VERSION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">1</bp:ID-VERSION>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5481.1</bp:COMMENT>

		  </bp:unificationXref>

		  <bp:catalysis rdf:ID="furin_activity_of_furin__Golgi_membrane_">

		    <bp:CONTROLLER rdf:resource="#furin__Golgi_membrane_" />

		    <bp:CONTROLLED rdf:resource="#Notch_1_precursor_cleaved_to_form_a_heterodimer" />

		    <bp:DIRECTION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PHYSIOL-LEFT-TO-RIGHT</bp:DIRECTION>

		    <bp:CONTROL-TYPE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">ACTIVATION</bp:CONTROL-TYPE>

		    <bp:XREF rdf:resource="#furin_activity" />

		    <bp:XREF rdf:resource="#Reactome156993" />

		    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		  </bp:catalysis>

		  <bp:sequenceParticipant rdf:ID="furin__Golgi_membrane_">

		    <bp:PHYSICAL-ENTITY rdf:resource="#UniProt_P09958_Furin_precursor__EC_3_4_21_75___Paired_basic_amino_acid_residue_cleaving_enzyme___PACE___Dibasic_processing_enzyme_" />

		    <bp:SEQUENCE-FEATURE-LIST rdf:resource="#Length_108_794_" />

		  </bp:sequenceParticipant>

		  <bp:openControlledVocabulary rdf:ID="Golgi_membrane">

		    <bp:TERM rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Golgi membrane</bp:TERM>

		    <bp:XREF rdf:resource="#GO_0000139" />

		  </bp:openControlledVocabulary>

		  <bp:unificationXref rdf:ID="GO_0000139">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">GO</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">0000139</bp:ID>

		  </bp:unificationXref>

		  <bp:sequenceFeature rdf:ID="Length_108_794_">

		    <bp:FEATURE-TYPE rdf:resource="#LengthFeature" />

		    <bp:FEATURE-LOCATION rdf:resource="#SequenceInterval2" />

		  </bp:sequenceFeature>

		  <bp:sequenceInterval rdf:ID="SequenceInterval2">

		    <bp:SEQUENCE-INTERVAL-BEGIN rdf:resource="#SequenceSite4" />

		    <bp:SEQUENCE-INTERVAL-END rdf:resource="#SequenceSite5" />

		  </bp:sequenceInterval>

		  <bp:sequenceSite rdf:ID="SequenceSite4">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">108</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		  </bp:sequenceSite>

		  <bp:sequenceSite rdf:ID="SequenceSite5">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">794</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		  </bp:sequenceSite>

		  <bp:relationshipXref rdf:ID="furin_activity">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">GO</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">0004276</bp:ID>

		    <bp:RELATIONSHIP-TYPE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">GO molecular function</bp:RELATIONSHIP-TYPE>

		  </bp:relationshipXref>

		  <bp:unificationXref rdf:ID="Reactome156993">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">156993</bp:ID>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&amp;ID=156993</bp:COMMENT>

		  </bp:unificationXref>

		  <bp:unificationXref rdf:ID="Reactome157042">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">157042</bp:ID>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&amp;ID=157042</bp:COMMENT>

		  </bp:unificationXref>

		  <bp:unificationXref rdf:ID="REACT_1127.2">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">REACT_1127</bp:ID>

		    <bp:ID-VERSION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2</bp:ID-VERSION>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1127.2</bp:COMMENT>

		  </bp:unificationXref>

		  <bp:publicationXref rdf:ID="Pubmed_9653148">

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">9653148</bp:ID>

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pubmed</bp:DB>

		    <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#int">1998</bp:YEAR>

		    <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">The Notch1 receptor is cleaved constitutively by a furin-like convertase</bp:TITLE>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Logeat, F</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">LeBail, O</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Jarriault, S</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Seidah, NG</bp:AUTHORS>

		    <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Proc Natl Acad Sci U S A 95:8108-12</bp:SOURCE>

		  </bp:publicationXref>
		 <bp:publicationXref rdf:ID="Pubmed_9244302">

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">9244302</bp:ID>

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pubmed</bp:DB>

		    <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#int">1997</bp:YEAR>

		    <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane</bp:TITLE>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Blaumueller, CM</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Qi, H</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Zagouras, P</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Artavanis-Tsakonas, S</bp:AUTHORS>

		    <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell 90:281-91</bp:SOURCE>

		  </bp:publicationXref>
	</Biopax>

    <Graphics Color="Transparent">

      <Point x="3315.0" y="1875.0" Head="Arrow" GraphRef="feb" />

      <Point x="5055.0" y="1875.0" GraphRef="cc2" />

    </Graphics>

    </Line>
    <Group GroupId="ef1" Type="Complex">
		<Biopax>
 			<bp:complex rdf:ID="NTM_NEC_1_heterodimer__Golgi_lumen_1">

			    <bp:COMPONENTS rdf:resource="#Notch_1_Transmembrane_fragment__NTM___Golgi_lumen_" />

			    <bp:COMPONENTS rdf:resource="#Notch_1_Extracellular_fragment__NEC___Golgi_lumen_" />

			    <bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">NTM-NEC 1 heterodimer [Golgi lumen]</bp:NAME>

			    <bp:SHORT-NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">NTM-NEC 1 heterodimer</bp:SHORT-NAME>

			    <bp:XREF rdf:resource="#Reactome157091" />

			    <bp:XREF rdf:resource="#REACT_5481.1" />

			    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		  </bp:complex>
		</Biopax>
	</Group>

    <InfoBox CenterX="0.0" CenterY="0.0" />

</Pathway>

To summarize the information that's added:

  • Line
    • pathwayStep
      • Participants
        • Notch_1_precursor_cleaved_to_form_a_heterodimer (biochemicalReaction)
        • furin_activity_of_furinGolgi_membrane_ (catalysis)
        • Notch_1_heterodimer_trafficks_to_the_plasma_membraneStep (next step)
    • biochemicalReaction (Notch_1_precursor_cleaved_to_form_a_heterodimer)
      • EC number
      • XRef to reactome
      • in/output (left, right)
        • Notch_1_receptor_precursorGolgi_lumen_1
          • Refers to BioPAX protein in DataNode? 'Notch precursor'
        • NTM_NEC_1_heterodimerGolgi_lumen_
          • Refers to BioPAX complex in Group 'ef1'
    • catalysis (furin_activity_of_furinGolgi_membrane_)
    • PublicationXRefs to pubmed
  • DataNode? 'furin'
    • protein (referred to in catalysis)
  • DataNode? 'Notch precursor'
    • protein (referred to in Notch_1_receptor_precursorGolgi_lumen_1)
  • Group 'ef1'
    • complex
      • Participants
        • Notch_1_Transmembrane_fragmentNTM_Golgi_lumen_
          • Refers to sequenceParticipant in DataNode? 'Notch 1 TM'
        • Notch_1_Transmembrane_fragmentNEC_Golgi_lumen_
          • Refers to sequenceParticipant in DataNode? 'Notch 1 EC'
    • DataNode? 'Notch TM'
      • sequenceParticipant (Notch_1_Transmembrane_fragmentNTM_Golgi_lumen_)
        • The sequence locations of this cleaved part
    • DataNode? 'Notch EC' (Notch_1_Transmembrane_fragmentNEC_Golgi_lumen_)
      • The sequence locations of this cleaved part

Complete pathway with Groups and BioPAX

[...]

Including NetPath? information

[...]

Making PathVisio ready

Groups

  • Manually added group elements are currently lost when saving the pathway in PathVisio
  • No layout options (stack, collapse) for group elements yet

BioPAX

  • Manually added BioPAX elements are currently lost when saving the pathway in PathVisio
  • No way to add BioPAX via a UI yet

Validation of BioPAX in PathVisio

We currently 'link' the GPML elements to their corresponding BioPAX element by nesting the BioPAX snippet in the GPML element's body. How do we ensure that this BioPAX element contains code that's compatible with the GPML elements that it's nested in. E.g., how do we ensure that DataNode? with type 'Protein' has a BioPAX snippet containing one, and only one bp:protein BioPAX element. What would happen if we don't enforce this? Could something go wrong when adding BioPAX properties that will be derived from the GPML (XREF, sequenceParticipant)? [...]

Export to a BioPAX only file

We finally want to be able to export the hybrid GPML/BioPAX file to a BioPAX-only file (without the layout information off course). This could be as simple as putting all text in the Biopax elements in a rdf:RDF tag in a single owl file: 

<?xml version="1.0" encoding="UTF-8"?>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bp="http://www.biopax.org/release/biopax-level2.owl#" xmlns:rdfs="http://www.w3.org/2000/01/rdf-schema#" xmlns:owl="http://www.w3.org/2002/07/owl#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" xmlns="http://www.reactome.org/biopax#" xml:base="http://www.reactome.org/biopax">
<owl:Ontology rdf:about="">
	<owl:imports rdf:resource="http://www.biopax.org/release/biopax-level2.owl" />
	<rdfs:comment rdf:datatype="http://www.w3.org/2001/XMLSchema#string">BioPAX pathway converted from "Notch Signaling Pathway" in the Reactome database.</rdfs:comment>
</owl:Ontology>
[[code form Biopax tags will go here]]
<rdf:RDF>
</pre>

However, we have to derive more information from GPML. For DataNodes we need to add the XREF properties, for Groups of type 'Complex' we need to add bp:sequenceParticipants. For linked nodes/edges we can create interactions, if they are not available yet. [...]

== Other issues ==
=== Duplicate graphical elements ===
The pathway drawing often contains duplicate element, e.g. the homo-dimer of presenilin is there twice. This will mean that we will store a lot of redundant BioPAX information (the images are duplicate, they mean the same thing). With the current approach (where the BioPAX is linked to the GPML element because it's nested in that element) we can't store all shared BioPAX elements in a central place, because then we wouldn't be able to link them. If we can assume that every GPML element can have only one BioPAX element, then we could store all BioPAX code in a single tag and give every GPML element a 'BiopaxRef' attribute that contains the name of the BioPAX element it links to in the BioPAX code. Here's an example:

<pre>
<?xml version="1.0" encoding="ISO-8859-1"?>

<Pathway xmlns="http://genmapp.org/GPML/2007" xmlns:bp="http://www.biopax.org/release/biopax-level2.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:rdfs="http://www.w3.org/2000/01/rdf-schema#" xmlns:owl="http://www.w3.org/2002/07/owl#" Name="Gamma-secretase complex example" Data-Source="GenMAPP 2.0" Version="20070427">
Name="Maturation of Notch precursor" Data-Source="GenMAPP 2.0" Version="20070430">

    <Graphics BoardWidth="8000.0" BoardHeight="5000.0" WindowWidth="18000.0" WindowHeight="12000.0" />

    <DataNode TextLabel="Furin" Type="Unknown" GraphId="e0a" BiopaxRef="#furin__Golgi_membrane_">

        <Graphics Color="Transparent" CenterX="5655.0" CenterY="1860.0" Width="1050.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 TM" Type="Unknown" GraphId="a04" GroupRef="ef1" BiopaxRef="#Notch_1_Transmembrane_fragment__NTM___Golgi_lumen_">

        <Graphics Color="Transparent" CenterX="3990.0" CenterY="1620.0" Width="1200.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 polypeptide" Type="Unknown" GraphId="feb" BiopaxRef="#Notch_1_receptor_precursor__Golgi_lumen_1">

        <Graphics Color="Transparent" CenterX="2160.0" CenterY="1845.0" Width="1950.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <DataNode TextLabel="Notch1 EC" Type="Unknown" GraphId="cc2" GroupRef="ef1" BiopaxRef="#Notch_1_Transmembrane_fragment__NEC___Golgi_lumen_">

        <Graphics Color="Transparent" CenterX="6750.0" CenterY="1860.0" Width="1050.0" Height="300.0" />

        <Xref Database="" ID="" />

    </DataNode>

    <Line>

    <Graphics Color="Transparent">

      <Point x="3315.0" y="1875.0" Head="Arrow" GraphRef="feb" />

      <Point x="5055.0" y="1875.0" GraphRef="cc2" />

    </Graphics>

    </Line>
    <Group GroupId="ef1" Type="Complex" BiopaxRef="#NTM_NEC_1_heterodimer__Golgi_lumen_1"/>

    <InfoBox CenterX="0.0" CenterY="0.0" />
	<Biopax>
		<bp:protein rdf:ID="UniProt_P46531_Neurogenic_locus_notch_homolog_protein_1_precursor__Notch_1___hN1___Translocation_associated_notch_protein_TAN_1_">

		    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		    <bp:ORGANISM rdf:resource="#Homo_sapiens" />

		    <bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">UniProt:P46531 Neurogenic locus notch homolog protein 1 precursor (Notch 1) (hN1) (Translocation-associated notch protein TAN-1)</bp:NAME>

		    <bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">NOTCH1</bp:SYNONYMS>

		    <bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">TAN1</bp:SYNONYMS>

		    <bp:XREF rdf:resource="#UniProt_P46531" />

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">FUNCTION: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBP-J kappa and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May be important for normal lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms. Involved in the maturation of both CD4+ and CD8+ cells in the thymus (By similarity). SUBUNIT: Heterodimer of a C-terminal fragment N(TM) and a N- terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity). Interacts with DTX1 and DTX2. SUBCELLULAR LOCATION: Type I membrane protein. Following proteolytical processing NICD is translocated to the nucleus (By similarity). TISSUE SPECIFICITY: In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues. PTM: Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C- terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity). PTM: Phosphorylated (By similarity). DISEASE: NOTCH1 truncation is associated with T-cell acute lymphoblastic leukemia. SIMILARITY: Belongs to the NOTCH family. SIMILARITY: Contains 5 ANK repeats. SIMILARITY: Contains 36 EGF-like domains. SIMILARITY: Contains 3 Lin/Notch repeats.</bp:COMMENT>

		  </bp:protein>
		<bp:sequenceParticipant rdf:ID="Notch_1_Extracellular_fragment__NEC___Golgi_lumen_">

		    <bp:CELLULAR-LOCATION rdf:resource="#Golgi_lumen" />

		    <bp:PHYSICAL-ENTITY rdf:resource="#UniProt_P46531_Neurogenic_locus_notch_homolog_protein_1_precursor__Notch_1___hN1___Translocation_associated_notch_protein_TAN_1_" />

		    <bp:SEQUENCE-FEATURE-LIST rdf:resource="#Length_19__1_" />

		    <bp:STOICHIOMETRIC-COEFFICIENT rdf:datatype="http://www.w3.org/2001/XMLSchema#double">1</bp:STOICHIOMETRIC-COEFFICIENT>

		</bp:sequenceParticipant>

		<bp:sequenceFeature rdf:ID="Length_19__1_">

		    <bp:FEATURE-TYPE rdf:resource="#LengthFeature" />

		    <bp:FEATURE-LOCATION rdf:resource="#SequenceInterval1" />

		</bp:sequenceFeature>

		<bp:sequenceInterval rdf:ID="SequenceInterval1">

		    <bp:SEQUENCE-INTERVAL-BEGIN rdf:resource="#SequenceSite2" />

		    <bp:SEQUENCE-INTERVAL-END rdf:resource="#SequenceSite3" />

		</bp:sequenceInterval>

		<bp:sequenceSite rdf:ID="SequenceSite2">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">19</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		</bp:sequenceSite>

		<bp:sequenceSite rdf:ID="SequenceSite3">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">-1</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		</bp:sequenceSite>
 		<bp:sequenceParticipant rdf:ID="Notch_1_Transmembrane_fragment__NTM___Golgi_lumen_">

		    <bp:CELLULAR-LOCATION rdf:resource="#Golgi_lumen" />

		    <bp:PHYSICAL-ENTITY rdf:resource="#UniProt_P46531_Neurogenic_locus_notch_homolog_protein_1_precursor__Notch_1___hN1___Translocation_associated_notch_protein_TAN_1_" />

		    <bp:SEQUENCE-FEATURE-LIST rdf:resource="#Length_1_2556_" />

		    <bp:STOICHIOMETRIC-COEFFICIENT rdf:datatype="http://www.w3.org/2001/XMLSchema#double">1</bp:STOICHIOMETRIC-COEFFICIENT>

		</bp:sequenceParticipant>

		<bp:sequenceFeature rdf:ID="Length_1_2556_">

		    <bp:FEATURE-TYPE rdf:resource="#LengthFeature" />

		    <bp:FEATURE-LOCATION rdf:resource="#SequenceInterval" />

		</bp:sequenceFeature>

		<bp:openControlledVocabulary rdf:ID="LengthFeature">

		    <bp:TERM rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Chain Coordinates</bp:TERM>

		</bp:openControlledVocabulary>

		<bp:sequenceInterval rdf:ID="SequenceInterval">

		    <bp:SEQUENCE-INTERVAL-BEGIN rdf:resource="#SequenceSite" />

		    <bp:SEQUENCE-INTERVAL-END rdf:resource="#SequenceSite1" />

		</bp:sequenceInterval>

		<bp:sequenceSite rdf:ID="SequenceSite">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">1</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

	  	</bp:sequenceSite>

	  	<bp:sequenceSite rdf:ID="SequenceSite1">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">2556</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		</bp:sequenceSite>
		<bp:protein rdf:ID="UniProt_P09958_Furin_precursor__EC_3_4_21_75___Paired_basic_amino_acid_residue_cleaving_enzyme___PACE___Dibasic_processing_enzyme_">

		    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		    <bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">UniProt:P09958 Furin precursor (EC 3.4.21.75) (Paired basic amino acid residue cleaving enzyme) (PACE) (Dibasic processing enzyme)</bp:NAME>

		    <bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PACE</bp:SYNONYMS>

		    <bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">FUR</bp:SYNONYMS>

		    <bp:SYNONYMS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">FURIN</bp:SYNONYMS>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">FUNCTION: Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif. CATALYTIC ACTIVITY: Release of mature proteins from their proproteins by cleavage of Arg-Xaa-Yaa-Arg-|-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and von Willebrand factor from their respective precursors. COFACTOR: Calcium. ENZYME REGULATION: Could be inhibited by the not secondly cleaved propeptide. SUBUNIT: Interacts with FLNA (By similarity). Binds to PACS1 which mediates TGN localization and connection to clathrin adapters. SUBCELLULAR LOCATION: Seems to be localized intracellularly to the trans Golgi network. Propeptide cleavage is a prerequisite for exit of furin molecules out of the endoplasmic reticulum (ER). Second cleavage in the propeptide occur in the trans Golgi network (TGN), which is followed by the release of the propeptide bound to furin and the activation of furin. TISSUE SPECIFICITY: Seems to be expressed ubiquitously. DOMAIN: Contains a cytoplasmic domain responsible for its TGN localization and recycling from the cell surface. PTM: The propeptide is autocatalytically removed through an intramolecular cleavage probably in the endoplasmic reticulum (ER). In the TGN the second cleavage in the propeptide could lead to the activation of furin. PTM: Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms. SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily. SIMILARITY: Contains 1 homo B/P domain.</bp:COMMENT>

		</bp:protein>
		<bp:pathwayStep rdf:ID="Notch_1_precursor_cleaved_to_form_a_heterodimerStep">

    		<bp:STEP-INTERACTIONS rdf:resource="#Notch_1_precursor_cleaved_to_form_a_heterodimer" />

    		<bp:NEXT-STEP rdf:resource="#Notch_1_heterodimer_trafficks_to_the_plasma_membraneStep" />

    		<bp:STEP-INTERACTIONS rdf:resource="#furin_activity_of_furin__Golgi_membrane_" />

  		</bp:pathwayStep>
		<bp:biochemicalReaction rdf:ID="Notch_1_precursor_cleaved_to_form_a_heterodimer">

		    <bp:LEFT rdf:resource="#Notch_1_receptor_precursor__Golgi_lumen_1" />

		    <bp:RIGHT rdf:resource="#NTM_NEC_1_heterodimer__Golgi_lumen_" />

		    <bp:EC-NUMBER rdf:datatype="http://www.w3.org/2001/XMLSchema#string">3.4.21.75</bp:EC-NUMBER>

		    <bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Notch 1 precursor cleaved to form a heterodimer</bp:NAME>

		    <bp:SHORT-NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Notch 1 precursor cleaved to form a heterodimer</bp:SHORT-NAME>

		    <bp:XREF rdf:resource="#Reactome157042" />

		    <bp:XREF rdf:resource="#REACT_1127.2" />

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">At the beginning of this reaction, 1 molecule of 'Notch 1 receptor precursor' is present. At the end of this reaction, 1 molecule of 'NTM-NEC 1 heterodimer' is present.&lt;br&gt;&lt;br&gt; This reaction takes place in the 'Golgi lumen' and  is mediated by the 'furin activity' of 'furin'.&lt;br&gt;</bp:COMMENT>

		    <bp:XREF rdf:resource="#Pubmed_9653148" />

		    <bp:XREF rdf:resource="#Pubmed_9244302" />

		    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		</bp:biochemicalReaction>

		<bp:sequenceParticipant rdf:ID="Notch_1_receptor_precursor__Golgi_lumen_1">

		    <bp:CELLULAR-LOCATION rdf:resource="#Golgi_lumen" />

		    <bp:PHYSICAL-ENTITY rdf:resource="#UniProt_P46531_Neurogenic_locus_notch_homolog_protein_1_precursor__Notch_1___hN1___Translocation_associated_notch_protein_TAN_1_" />

		    <bp:STOICHIOMETRIC-COEFFICIENT rdf:datatype="http://www.w3.org/2001/XMLSchema#double">1</bp:STOICHIOMETRIC-COEFFICIENT>

		</bp:sequenceParticipant>

		<bp:physicalEntityParticipant rdf:ID="NTM_NEC_1_heterodimer__Golgi_lumen_">

		    <bp:CELLULAR-LOCATION rdf:resource="#Golgi_lumen" />

		    <bp:PHYSICAL-ENTITY rdf:resource="#NTM_NEC_1_heterodimer__Golgi_lumen_1" />

		    <bp:STOICHIOMETRIC-COEFFICIENT rdf:datatype="http://www.w3.org/2001/XMLSchema#double">1</bp:STOICHIOMETRIC-COEFFICIENT>

		</bp:physicalEntityParticipant>

		<bp:unificationXref rdf:ID="Reactome157091">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">157091</bp:ID>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&amp;ID=157091</bp:COMMENT>

		</bp:unificationXref>

		<bp:unificationXref rdf:ID="REACT_5481.1">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">REACT_5481</bp:ID>

		    <bp:ID-VERSION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">1</bp:ID-VERSION>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5481.1</bp:COMMENT>

		</bp:unificationXref>

		<bp:catalysis rdf:ID="furin_activity_of_furin__Golgi_membrane_">

		    <bp:CONTROLLER rdf:resource="#furin__Golgi_membrane_" />

		    <bp:CONTROLLED rdf:resource="#Notch_1_precursor_cleaved_to_form_a_heterodimer" />

		    <bp:DIRECTION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PHYSIOL-LEFT-TO-RIGHT</bp:DIRECTION>

		    <bp:CONTROL-TYPE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">ACTIVATION</bp:CONTROL-TYPE>

		    <bp:XREF rdf:resource="#furin_activity" />

		    <bp:XREF rdf:resource="#Reactome156993" />

		    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		</bp:catalysis>

		<bp:sequenceParticipant rdf:ID="furin__Golgi_membrane_">

		    <bp:PHYSICAL-ENTITY rdf:resource="#UniProt_P09958_Furin_precursor__EC_3_4_21_75___Paired_basic_amino_acid_residue_cleaving_enzyme___PACE___Dibasic_processing_enzyme_" />

		    <bp:SEQUENCE-FEATURE-LIST rdf:resource="#Length_108_794_" />

		</bp:sequenceParticipant>

		<bp:openControlledVocabulary rdf:ID="Golgi_membrane">

		    <bp:TERM rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Golgi membrane</bp:TERM>

		    <bp:XREF rdf:resource="#GO_0000139" />

		</bp:openControlledVocabulary>

		<bp:unificationXref rdf:ID="GO_0000139">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">GO</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">0000139</bp:ID>

		</bp:unificationXref>

		<bp:sequenceFeature rdf:ID="Length_108_794_">

		    <bp:FEATURE-TYPE rdf:resource="#LengthFeature" />

		    <bp:FEATURE-LOCATION rdf:resource="#SequenceInterval2" />

		</bp:sequenceFeature>

		<bp:sequenceInterval rdf:ID="SequenceInterval2">

		    <bp:SEQUENCE-INTERVAL-BEGIN rdf:resource="#SequenceSite4" />

		    <bp:SEQUENCE-INTERVAL-END rdf:resource="#SequenceSite5" />

		</bp:sequenceInterval>

		<bp:sequenceSite rdf:ID="SequenceSite4">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">108</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		</bp:sequenceSite>

		<bp:sequenceSite rdf:ID="SequenceSite5">

		    <bp:SEQUENCE-POSITION rdf:datatype="http://www.w3.org/2001/XMLSchema#integer">794</bp:SEQUENCE-POSITION>

		    <bp:POSITION-STATUS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">EQUAL</bp:POSITION-STATUS>

		</bp:sequenceSite>

		<bp:relationshipXref rdf:ID="furin_activity">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">GO</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">0004276</bp:ID>

		    <bp:RELATIONSHIP-TYPE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">GO molecular function</bp:RELATIONSHIP-TYPE>

		</bp:relationshipXref>

		<bp:unificationXref rdf:ID="Reactome156993">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">156993</bp:ID>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&amp;ID=156993</bp:COMMENT>

		</bp:unificationXref>

		<bp:unificationXref rdf:ID="Reactome157042">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">157042</bp:ID>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&amp;ID=157042</bp:COMMENT>

		</bp:unificationXref>

		<bp:unificationXref rdf:ID="REACT_1127.2">

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome</bp:DB>

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">REACT_1127</bp:ID>

		    <bp:ID-VERSION rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2</bp:ID-VERSION>

		    <bp:COMMENT rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1127.2</bp:COMMENT>

		</bp:unificationXref>

		<bp:publicationXref rdf:ID="Pubmed_9653148">

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">9653148</bp:ID>

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pubmed</bp:DB>

		    <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#int">1998</bp:YEAR>

		    <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">The Notch1 receptor is cleaved constitutively by a furin-like convertase</bp:TITLE>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Logeat, F</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">LeBail, O</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Jarriault, S</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Seidah, NG</bp:AUTHORS>

		    <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Proc Natl Acad Sci U S A 95:8108-12</bp:SOURCE>

		</bp:publicationXref>
		<bp:publicationXref rdf:ID="Pubmed_9244302">

		    <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">9244302</bp:ID>

		    <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pubmed</bp:DB>

		    <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#int">1997</bp:YEAR>

		    <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane</bp:TITLE>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Blaumueller, CM</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Qi, H</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Zagouras, P</bp:AUTHORS>

		    <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Artavanis-Tsakonas, S</bp:AUTHORS>

		    <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell 90:281-91</bp:SOURCE>

		</bp:publicationXref>
 		<bp:complex rdf:ID="NTM_NEC_1_heterodimer__Golgi_lumen_1">

			    <bp:COMPONENTS rdf:resource="#Notch_1_Transmembrane_fragment__NTM___Golgi_lumen_" />

			    <bp:COMPONENTS rdf:resource="#Notch_1_Extracellular_fragment__NEC___Golgi_lumen_" />

			    <bp:NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">NTM-NEC 1 heterodimer [Golgi lumen]</bp:NAME>

			    <bp:SHORT-NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">NTM-NEC 1 heterodimer</bp:SHORT-NAME>

			    <bp:XREF rdf:resource="#Reactome157091" />

			    <bp:XREF rdf:resource="#REACT_5481.1" />

			    <bp:DATA-SOURCE rdf:resource="#ReactomeDataSource" />

		 </bp:complex>
	</Biopax>

</Pathway>

BioPAX Conversion

Thomas: The sections above are notes from my attempt to convert a Reactome pathway to GPML (including BioPAX). It’s probably not really useful and most issues are really GPML/PathVisio related (e.g. how to represent complexes in a compact, clear way). It also doesn’t cover the conversion really well, it’s more about how to use BioPAX within GPML. Also, it’s a bit out of date. I changed the way GPML handles BioPAX according to the proposal in the last section ([#Duplicate_graphical_elements]). Another update is that BioPAX is now used in the WikiPathways? applet to store literature references (that’s the only use of BioPAX in GPML right now), it could be useful to look at this code. Try to add some literature references to a pathway on WikiPathways? and save it as GPML, then you see how it’s stored as BioPAX and linked to the GPML elements using the BiopaxRef? element. My current idea of how we should do the conversion. The conversion itself will be pretty similar to the Cytoscape converter:

  • Convert all datanodes to a bp:physicalEntity subclass
  • Convert all lines that connect a datanode to a bp:physicalInteraction
  • Convert all groups (with style stack/complex) to a bp:complex
  • Create a bp:pathway element (I’m not sure how to set the bp:pathwayStep properties)

And all elements of which we don’t know the semantic meaning of (labels, shapes) are lost. The resulting file will be a kind of skeleton interaction network. All other semantic information (e.g. what are the characteristics of the interaction) should already be stored in BioPAX syntax within GPML (by using the Biopax element in GPML in combination with the BiopaxRef? element, similar to literature references). So we should merge this code into the generated physicalEntities and physicalInteractions.

Interface

There is no user interface to add BioPAX information to a line, datanode or group yet in PathVisio or the WikiPathways? applet, but we can create an example pathway where we put in some code manually.

Java API to BioPAX

For the actual implementation of the conversion, I wonder what’s the best way to handle BioPAX in Java. It would be great to have a java API to BioPAX. Currently for the literature references, I’ve implemented a class that reflects the BioPAX PublicationXRef class myself and my plan is to do this for all BioPAX elements which we are going to support (which probably aren’t that many). However, if there is already a java library for BioPAX, it could save us a lot of work. I did some attempts to work with PaxTools?, but it didn’t provide the functionality I needed (e.g. validating the BioPAX code) and I think it’s too heavy (a lot of dependencies on large jar files) for our simple purpose of converting a pathway. Could you ask the BioPAX people if they have experience with other conversion tools in java? What do they use, all custom build java model of BioPAX, or an existing library? AP: From the BioPAX meeting I attended in Oct 2007, it was clear that the way to go is with PaxTools?. Emek gave a convincing presentation on the topic. A new version of paxtools will be released shortly after BioPAX Level 3 (due by end of Dec 2007) that will address many prior issues, especially size.

  • Here are some of the key points/features for Paxtools:
    • POJO beans
    • OO interpretation of the OWL
    • current i/o layer uses Jena thus heavyweight; plan to plugout Jena in future, if demanded
    • efficient, once in Java
    • validates and fails-fast
    • additional, complex rule validation is possible with separate code by Emek (not checked in)
    • provides JPA and Lucene persistence and query
    • level 2 core is stable
    • level 3 core should follow biopax release

There is a mailing list for BioPAX that we should join in order to ask questions and monitor progress. In particular, we should lobby for changes we want to paxtools to make it work for us. Emek was clear that he is very eager to have people use paxtools and user feedback has a direct effect on what he does with the project. And as you can see from the activity on the list, I think we would have a large stake at this early point in dev:  http://groups.google.com/group/biopax-discussion

Example Pathway

Well, I think the best way to tackle the problem is to create a simple example pathway a lot of BioPAX information and try to convert it manually. I’m not sure if the Reactome pathway I picked is suitable for this, maybe we should even create a non-existing pathway just as example.

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