The power of graphs to analyze biological data

1. the power of graphs for analyzing biological datasets
Davy Suvee
Janssen Pharmaceutica

2. about me
who am i ...
➡ working as an it lead / software architect @ janssen pharmaceutica
• dealing with big scientific data sets
• hands-on expertise in big data and NoSQL technologies
➡ founder of datablend
• provide big data and NoSQL consultancy
Davy Suvee • share practical knowledge and big data use cases via blog
@DSUVEE

3. outline
➡ getting visual insights into big data sets
★ gene expression clustering (mongodb, Neo4j, Gephi)
★ Mutation prevalence (cassandra, Neo4j, Gephi)
➡ fluxgraph, a time machine for you graphs ...

4. insights in big data
➡ typical approach through warehousing
★ star schema with fact tables and dimension tables

5. insights in big data
➡ typical approach through warehousing
★ star schema with fact tables and dimension tables

6. insights in big data
★ real-time visualization
★ filtering
★ metrics
★ layouting
1, 2
★ modular
1. http://gephi.org/plugins/neo4j-graph-database-support/ 2. http://github.com/datablend/gephi-blueprints-plugin

7. gene expression clustering
➡ oncology data set:
★ 4.800 samples
★ 27.000 genes
➡ Question:
★ for a particular subset of samples,
which genes are co-expressed?

8. mongodb for storing gene expressions
{ "_id" : { "$oid" : "4f1fb64a1695629dd9d916e3"} ,
"sample_name" : "122551hp133a21.cel" ,
"genomics_id" : 122551 ,
"sample_id" : 343981 ,
"donor_id" : 143981 ,
"sample_type" : "Tissue" ,
"sample_site" : "Ascending colon" ,
"pathology_category" : "MALIGNANT" ,
"pathology_morphology" : "Adenocarcinoma" ,
"pathology_type" : "Primary malignant neoplasm of colon" ,
"primary_site" : "Colon" ,
"expressions" : [ { "gene" : "X1_at" , "expression" : 5.54217719084415} ,
{ "gene" : "X10_at" , "expression" : 3.92335121981739} ,
{ "gene" : "X100_at" , "expression" : 7.81638155662255} ,
{ "gene" : "X1000_at" , "expression" : 5.44318512260619} ,
… ]
}

9. pearson correlation through map-reduce
x y
pearson correlation 43 99
21 65
25 79 0,52
42 75
57 87
59 81

10. co-expression graph
➡ create a node for each gene
➡ if correlation between two genes >= 0.8, draw an edge between both nodes

11. co-expression graph

12. graphs and time ...
➡ reproducible graph state
➡ towards a time-aware graph ...
➡ fluxgraph: a blueprints-compatible graph on top of Datomic
➡ make FluxGraph fully time-aware
★ travel your graph through time
★ time-scoped iteration of vertices and edges
★ temporal graph comparison

13. travel through time
FluxGraph fg = new FluxGraph();

14. travel through time
FluxGraph fg = new FluxGraph();
Davy
Vertex davy = fg.addVertex();
davy.setProperty(“name”,”Davy”);

15. travel through time
FluxGraph fg = new FluxGraph();
Davy
Vertex davy = fg.addVertex();
davy.setProperty(“name”,”Davy”);
Peter
Vertex peter = ...

16. travel through time
FluxGraph fg = new FluxGraph();
Davy
Vertex davy = fg.addVertex();
davy.setProperty(“name”,”Davy”);
Peter
Vertex peter = ...
Vertex michael = ...
Michael

17. travel through time
FluxGraph fg = new FluxGraph();
Davy
kn
ow
Vertex davy = fg.addVertex();
s
davy.setProperty(“name”,”Davy”);
Peter
Vertex peter = ...
Vertex michael = ...
Edge e1 = Michael
fg.addEdge(davy, peter,“knows”);

18. travel through time
Davy
Date checkpoint = new Date();
kn
ow
s
Peter
Michael

19. travel through time
Davy
Date checkpoint = new Date();
kn
ow
s
davy.setProperty(“name”,”David”); Peter
Michael

20. travel through time
David
Date checkpoint = new Date();
kn
ow
s
davy.setProperty(“name”,”David”); Peter
Michael

21. travel through time
David
Date checkpoint = new Date();
kn
ow
s
davy.setProperty(“name”,”David”); Peter
kn
Edge e2 =
ow
fg.addEdge(davy, michael,“knows”);
s
Michael

22. travel through time by default
time
kn
Davy ow David
Davy
s
kn
ow
checkpoint
s
current
Peter Peter
kn
ow
s
Michael Michael

23. travel through time
time
kn
Davy ow David
Davy
s
kn
ow
checkpoint
s
current
Peter Peter
kn
ow
s
Michael Michael
fg.setCheckpointTime(checkpoint);

24. time-scoped iteration
t1 t2 t3 tcurrrent
change change change
Davy Davy’ Davy’’ Davy’’’
➡ how to find the version of the vertex you are interested in?

25. time-scoped iteration
t1 t2 t3 tcurrrent
next next next
Davy Davy’ Davy’’ Davy’’’
previous previous previous

26. time-scoped iteration
t1 t2 t3 tcurrrent
next next next
Davy Davy’ Davy’’ Davy’’’
previous previous previous
Vertex previousDavy = davy.getPreviousVersion();

27. time-scoped iteration
t1 t2 t3 tcurrrent
next next next
Davy Davy’ Davy’’ Davy’’’
previous previous previous
Vertex previousDavy = davy.getPreviousVersion();
Iterable<Vertex> allDavy = davy.getNextVersions();

28. time-scoped iteration
t1 t2 t3 tcurrrent
next next next
Davy Davy’ Davy’’ Davy’’’
previous previous previous
Vertex previousDavy = davy.getPreviousVersion();
Iterable<Vertex> allDavy = davy.getNextVersions();
Iterable<Vertex> selDavy = davy.getPreviousVersions(filter);

29. time-scoped iteration
t1 t2 t3 tcurrrent
next next next
Davy Davy’ Davy’’ Davy’’’
previous previous previous
Vertex previousDavy = davy.getPreviousVersion();
Iterable<Vertex> allDavy = davy.getNextVersions();
Iterable<Vertex> selDavy = davy.getPreviousVersions(filter);
Interval valid = davy.getTimerInterval();

30. time-scoped iteration
➡ When does an element change?
➡ vertex:
★ setting or removing a property
★ add or remove it from an edge
★ being removed

31. time-scoped iteration
➡ When does an element change?
➡ vertex: ➡ edge:
★ setting or removing a property ★ setting or removing a property
★ add or remove it from an edge ★ being removed
★ being removed

32. time-scoped iteration
➡ When does an element change?
➡ vertex: ➡ edge:
★ setting or removing a property ★ setting or removing a property
★ add or remove it from an edge ★ being removed
★ being removed
➡ ... and each element is time-scoped!

33. temporal graph comparison
David
Davy Davy
kn
kn
ow
ow
s
s
Peter what changed? Peter
kn
ow
s
Michael Michael
current checkpoint

34. temporal graph comparison
➡ difference (A , B) = union (A , B) - B
➡ ... as a (immutable) graph!

35. temporal graph comparison
➡ difference (A , B) = union (A , B) - B
➡ ... as a (immutable) graph! David
difference ( , )=
kn
ow
s

36. use case: longitudinal patient data
t1 t2 t3 t4 t5
smoking smoking death
patient patient patient patient patient
cancer cancer

37. use case: longitudinal patient data
➡ historical data for 15.000 patients over a period of 10 years (2001- 2010)

38. use case: longitudinal patient data
➡ historical data for 15.000 patients over a period of 10 years (2001- 2010)
➡ example analysis:
★ if a male patient is no longer smoking in 2005
★ what are the chances of getting lung cancer in 2010, comparing
patients that smoked before 2005
patients that never smoked

39. use case: longitudinal patient data
➡ get all male non-smokers in 2005
fg.setCheckpointTime(new DateTime(2005,12,31).toDate());

40. use case: longitudinal patient data
➡ get all male non-smokers in 2005
fg.setCheckpointTime(new DateTime(2005,12,31).toDate());
Iterator<Vertex> males =
fg.getVertices("gender", "male").iterator()

41. use case: longitudinal patient data
➡ get all male non-smokers in 2005
fg.setCheckpointTime(new DateTime(2005,12,31).toDate());
Iterator<Vertex> males =
fg.getVertices("gender", "male").iterator()
while (males.hasNext()) {
Vertex p2005 = males.next();
boolean smoking2005 =
p2005.getEdges(OUT,"smokingStatus").iterator().hasNext();
}

42. use case: longitudinal patient data
➡ which patients were smoking before 2005?
boolean smokingBefore2005 =
((FluxVertex)p2005).getPreviousVersions(new TimeAwareFilter() {
public TimeAwareElement filter(TimeAwareVertex element) {
return element.getEdges(OUT, "smokingStatus").iterator().hasNext()
? element : null;
}
}).iterator().hasNext();

43. use case: longitudinal patient data
➡ which patients have cancer in 2010
working set of smokers
Graph g =
fg.difference(smokerws,
time2010.toDate(),
time2005.toDate());

44. use case: longitudinal patient data
➡ which patients have cancer in 2010
working set of smokers
Graph g =
fg.difference(smokerws,
time2010.toDate(),
time2005.toDate());
➡ extract the patients that have an edge to the cancer node

45. Questions?