Embed Size (px)
DESCRIPTION
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.
Citation preview
Guided visual exploration of patient stratifications in cancer genomics
Nils GehlenborgHarvard Medical SchoolCenter for Biomedical Informatics
nils_gehlenborg!
Machine
Human
"
#
Machine
Human
"
#
Machine
Human
"
#
Data
INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
"
#
Data
“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)
INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
"
#
Data
HypothesesDiscoveries
KnowledgeCognition
x y1 y2
1.00 0.96 0.762.00 0.76 -0.143.00 -0.14 -0.914.00 -0.91 -0.845.00 -0.84 0.006.00 0.00 0.847.00 0.84 0.918.00 0.91 0.149.00 0.14 -0.7610.00 -0.76 -0.9611.00 -0.96 -0.28
-1
-0.5
0
0.5
1
1 2 3 4 5 6 7 8 9 10 11
INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
Hypotheses Discoveries
Knowledge
"
#
Data
Cognition
INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
Hypotheses Discoveries
Knowledge
"
#
Data|
Cognition
?
TCGAThe Cancer Genome Atlas
mRNA expression
microRNA expression
DNA methylation
protein expression
copy number variants
mutation calls
clinical parameters
Stratome
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)
Comparing Patient Sets across StratificationsPROBLEM 1
Comparing Patient Sets within StratificationsPROBLEM 2
Finding Relevant Stratifications and PathwaysPROBLEM 3
?
Knowledge-driven Exploration
Data-driven Exploration
Query
Rank
VisualizeStratifications
Clinical Params Pathways
Guided Exploration
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)
Query
Rank
VisualizeStratifications
Clinical Params Pathways
Guided Exploration
INTERPRETATION
GENERATIONCOMPUTATION
Machine
Human
Hypotheses Discoveries
Knowledge
"
#
Data|
Cognition
www.caleydo.org
www.caleydo.org
www.caleydo.org
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)
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
