This document discusses using graph analytics and linked open data to study pharmacology. It describes challenges in querying across heterogeneous life sciences linked open data sources and proposes a pattern-based approach to rewrite queries. An application called PhLeGrA is presented that generates a k-partite network by retrieving entities and relations from multiple sources to study drug mechanisms. Preliminary results using network-based algorithms to rank mechanisms are also discussed.

1. Graph Analytics in Pharmacology over the
Web of Life Sciences Linked Open Data
26th World Wide Web Conference (WWW)
Perth, 4th – 8th April 2017
MAU LIK R . KA MDA R A N D MA RK A . MU S E N
Stanford Center for Biomedical Informatics Research
maulikrk@stanford.edu

2. Linked Open Data (LOD) Cloud
Cyganiak, Richard et al. 2014
2

3. Life Sciences Linked Open Data (LSLOD) Cloud
…
3

4. 4

5. Semantic Web: Publishing Data as a Graph
5
589.25
mol_weight
Gleevec (Mol. Wt.: 589.25 g/mol, Half-Life: 18 hours)
inhibits PDGFR, involved in signal transduction.
“18 hours”
half-life
x-ref
Gleevec
DrugB: DB00619
Gleevec
Resource Description Framework (RDF)
Inhibits
target name
type
GO:0007165
(Signal
Transduction)
process
PDGFR
KEGG: D01441http://bio2rdf.org/kegg:D01441
http://bio2rdf.org/drugbank:DB00619
Uniform Resource Identifier

6. Semantic Web: Querying the Graph
< 1000
mol_weight
?half-life
x-ref
?
?
What are the half-lives of drugs that have
Mol. Wt < 1000 g/mol and inhibit proteins
involved in signal transduction?
SPARQL Query Language
6
Inhibits
?target name
type
GO:0007165
(Signal
Transduction)
process

7. Life Sciences Linked Open Data Cloud – query federation
• Challenges associated with retrieving information from LSLOD sources
• Pattern-based method to rewrite queries across LSLOD sources
• An application in mechanism-based pharmacovigilance - PhLeGrA
What this talk is about …
7

8. 8

9. Query Federation: Rewriting and executing
queries across different sources
QUERY FEDERATION
Drug
 molecular-weight < 1000
 target
 process = “GO:0007165”
 half-life
9Schwarte, et al. ISWC 2012
Drug
 molecular-weight < 1000
 target
 half-life
Drug
 molecular-weight < 1000
 target
 process = “GO:0007165”
What are the half-lives of drugs that
have Mol. Wt < 1000 g/mol and inhibit
proteins involved in signal transduction?

10. Heterogeneity in the LSLOD Cloud
10
Gleevec
molecular-weight
493.61 Gleevec
mol_weight
589.25
Label Mismatch: Different labels for classes, relations and attributes
(clinical features) (biological features)

11. Heterogeneity in the LSLOD Cloud
11
Gleevec
molecular-weight
493.61 Gleevec
mol_weight
589.25
Label Mismatch: Different labels for classes, relations and attributes
(clinical features) (biological features)

12. Heterogeneity in the LSLOD Cloud
12
Gleevec PDGFR
drug-target
Gleevec
Inhibits
PDGFR
target
name
type
PubMed: 21152856
source
Model Mismatch: Different graph patterns to capture granularity
Gleevec
molecular-weight
493.61 Gleevec
mol_weight
589.25
Label Mismatch: Different labels for classes, relations and attributes
(clinical features) (biological features)

13. Heterogeneity in the LSLOD Cloud
13
• Inconsistent Meanings
• Inconsistent URI labels for
classes, relations and attributes
• Inconsistent Attribute values for entities
• Inconsistent Graph patterns for
SPARQL queries
• Incomplete Relations between entities

14. Query Rewriting fails over the LSLOD Cloud
What are the half-lives of drugs that have Mol. Wt < 1000 g/mol and
inhibit proteins involved in signal transduction?
?s a <Drug>
?s <molecular-weight> ?mw
?s <target> ?protein
?s <half-life> ?hl
?mw < 1000 g/mol
?protein <hasGO> <GO:0007165>
?s a <Drug>
{?s <molecular-weight> ?mw}
{?s <half-life> ?hl}
?mw < 1000 g/mol
?s a <Drug>
{?s <target> ?protein}
?protein <hasGO> <GO:0007165>
Query
Rewriting
14

15. Using Graph Patterns for Query Rewriting
?Drug DrugBank:drug-target ?Protein
?Drug KEGG:target ?blank KEGG:link ?Protein
Mapping Rules:
15
?Drug hasTarget ?Protein

16. Using Graph Patterns for Query Rewriting
?Drug DrugBank:drug-target ?Protein
?Drug KEGG:target ?blank KEGG:link ?Protein
Mapping Rules:
What are the half-lives of drugs that have Mol. Wt < 1000 g/mol and
inhibit proteins involved in signal transduction?
?s a <Drug>
?s <hasMolWt> ?mw
?s <hasTarget> ?protein
?s <hasHalfLife> ?hl
?mw < 1000 g/mol
?protein <hasGO> <GO:0007165>
?s a <Drug>
{?s <molecular-weight> ?mw}
?s <drug-target> ?protein
{?s <half-life> ?hl}
?mw < 1000 g/mol
?s a <Drug>
?s <mol_wt> ?mw
{?s <target> ?protein_blank
?protein_blank <link> ?protein}
?protein <hasGO> <GO:0007165>
Query
RewriteQuery
Rewriting
16
?Drug hasTarget ?Protein

17. Life Sciences Linked Open Data Cloud – query federation
• Challenges associated with retrieving information from LSLOD sources
• Pattern-based method to rewrite queries across LSLOD sources
• An application in mechanism-based pharmacovigilance - PhLeGrA
What this talk is about …
17

18. PhLeGrA – Linked Graph Analytics in Pharmacology
18
Phlegra is a spider genus of the Salticidae family, commonly termed jumping spiders.

19. k-partite network will be generated as output
19

20. Entities and Relations from 4 different sources
are retrieved to create the k-partite Network
This k-partite network is generated in < 1 day
20

21. Query Federation overcomes heterogeneous
Distribution of Entities and Relations
R1: Drug hasTarget ProteinE1: Drug
• Similar and complete unique entities and relations exist between data sources
• Necessary to get the complete picture, but also determine sources of noise
21

22. Several underlying mechanisms are possible …
http://onto-apps.stanford.edu/phlegra 22

23. A graph analytics module to rank the mechanisms
23

24. Preliminary results using network-based
Apriori Algorithm for ranking mechanisms
24

25. The story so far …
25
Pattern-based federation methods can retrieve data
from multiple sources in the Life Sciences Linked Open
Data Cloud, and can enable development of advanced
methods for mechanism-based pharmacovigilance.
…

26. Acknowledgments
Musen Lab, Stanford
Biomedical Informatics Training Program
Michel Dumontier
US NIH Grant HG004028
26

27. PhLeGrA – Linked Graph Analytics in Pharmacology
27
www.stanford.edu/~maulikrk/research.html
www.onto-apps.stanford.edu/phlegra