Talk presented at the "Beyond the Genome 2014: Cancer Genomics" conference (10 October 2014) http://www.beyond-the-genome.com/2014/ Cancer is a heterogeneous disease, and molecular profiling of tumors from large cohorts has enabled characterization of new tumor subtypes. This is a prerequisite for improving personalized treatment and ultimately better patient outcomes. Potential tumor subtypes can be identified with methods such as unsupervised clustering or network-based stratification, which assign patients to sets based on high-dimensional molecular profiles. Detailed characterization of identified sets and their interpretation, however, remain a time-consuming exploratory process. To address these challenges, we have developed StratomeX (http://stratomex.caleydo.org), an interactive visualization tool that complements algorithmic approaches. StratomeX also integrates a computational framework for query-based guided exploration directly into the visualization, enabling discovery of novel relationships between patient sets and efficient generation and refinement of hypotheses about tumor subtypes. StratomeX enables analysts to efficiently compare multiple patient stratifications, to correlate patient sets with clinical information or genomic alterations, and to view the differences between molecular profiles across patient sets.

1. Guided visual exploration
of patient stratifications in
cancer genomics
Nils Gehlenborg
Harvard Medical School
Center for Biomedical Informatics
nils_gehlenborg

2. Machine
Human

3. Machine
Human

4. Machine
Human
Data

5. INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
Data

6. “In every chain of reasoning, the evidence of the last conclusion can
be no greater than that of the weakest link of the chain, whatever
may be the strength of the rest.”
- Thomas Reid, Essays on the Intellectual Powers of Man (1786)

7. INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
Data
Hypotheses
Discoveries
Knowledge
Cognition

8. x y1 y2
1.00 0.96 0.76
2.00 0.76 -0.14
3.00 -0.14 -0.91
4.00 -0.91 -0.84
5.00 -0.84 0.00
6.00 0.00 0.84
7.00 0.84 0.91
8.00 0.91 0.14
9.00 0.14 -0.76
10.00 -0.76 -0.96
11.00 -0.96 -0.28

9. -1
-0.5
0
0.5
1
1 2 3 4 5 6 7 8 9 10 11

10. INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
Hypotheses
Discoveries
Knowledge
Data
Cognition

11. INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
Hypotheses
Discoveries
Knowledge
Data|
Cognition

12. ?

14. TCGAThe Cancer Genome Atlas

16. mRNA expression
microRNA expression
DNA methylation
protein expression
copy number variants
mutation calls
clinical parameters

22. Stratome

23. Anthony92931 / Wikimedia Commons

26. StratomeX
A Lex, M Streit, H-J Schulz, C Partl, D Schmalstieg, PJ Park, N Gehlenborg, “StratomeX: Visual Anal-
ysis of Large-Scale Heterogeneous Genomics Data for Cancer Subtype Characterization“, Computer
Graphics Forum 31:1175-1184 (2012)
M Streit, A Lex, S Gratzl, C Partl, D Schmalstieg, H Pfister, PJ Park, N Gehlenborg, “Guided Visual
Exploration of Genomic Stratifications in Cancer“, Nature Methods 11:884-885 (2014)

27. Comparing Patient Sets
across StratificationsPROBLEM 1

37. Comparing Patient Sets
within StratificationsPROBLEM 2

49. Finding Relevant
Stratifications and PathwaysPROBLEM 3

50. ?

51. Knowledge-driven Exploration
Data-driven Exploration

53. Query
Rank
Visualize
Stratifications
Clinical Params
Pathways
Guided Exploration

55. LineUp
S Gratzl, A Lex, N Gehlenborg, H Pfister and M Streit, “LineUp: Visual Analysis of Multi-Attribute
Rankings“, IEEE Transactions on Visualization and Computer Graphics 19:2277-2286 (2013)

56. Query
Rank
Visualize
Stratifications
Clinical Params
Pathways
Guided Exploration

59. INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
Hypotheses
Discoveries
Knowledge
Data|
Cognition

61. www.caleydo.org

62. www.caleydo.org

63. www.caleydo.org

64. Domino
S Gratzl, N Gehlenborg, A Lex, H Pfister and M Streit, “Domino: Extracting, Comparing, and
Manipulating Subsets across Multiple Tabular Datasets“, IEEE Transactions on Visualization and
Computer Graphics (2014)

65. MD Anderson Cancer Center
University of Rostock
Peter J Park
Michael S Noble, David Heiman, Firehose Team, Gad Getz
Terrence Wu, Ian Watson, Lynda Chin
Harvard Medical School
Broad Institute of MIT & Harvard
Christian Partl, Dieter SchmalstiegGraz University of Technology
Johannes Kepler University Linz Samuel Gratzl, Marc Streit
Hans-Jörg Schulz
Acknowledgements
Harvard SEAS Alexander Lex, Hanspeter Pfister
Funding
NIH/NHGRI K99 HG007583 Pathway to Independence