Visualization Approaches for Biomedical Omics Data: Putting It All Together

Nils GehlenborgHarvard Medical SchoolCenter for Biomedical Informatics

nils_gehlenborg!

Why am I doing this?

Machine

Human

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INTERPRETATION

GENERATIONCOMPUTATION

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Human

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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

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Human

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Data

Hypotheses Discoveries

Knowledge Cognition

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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

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Hypotheses Discoveries

Knowledge

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Data|

Cognition

What are the data?

Biomedical Omics Data

DNA Icon by Darrin Higgins, from The Noun Project

Genome What is the DNA sequence?

Genome

sequencing of genomic DNAHOW?

single nucleotide variants (SNVs) copy number variants

complex structural variants

WHAT?

http://www.broadinstitute.org/igv

http://www.broadinstitute.org/igv

http://circos.ca, Krzywinski et al. 2009, Genome Research

Clark et al. 2009, PLoS Genetics

source: Human

destination: Lizardchr1

chr2

chr3

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chr1

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chrX

chrY

chr3

chr1

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chra

chrb

chrc

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saturationline

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10Mb

chr3

go to:

chr3 chr2

51280143 152008850

51709189 152345239

orientation:

match

inversion

invert

out in

http://www.mizbee.org

http://genome.lbl.gov/vista

Genome

Transcriptome

What is the DNA sequence?

Which genes are active?

Transcriptome

sequencing of mRNA/microRNA molecules microarray-based hybridization

HOW?

abundance of transcripts/genes/isoformsWHAT?

http://research.fhcrc.org/mcintosh/en/tools.html

http://miso.readthedocs.org/en/latest/sashimi.html#visualizing-and-plotting-miso-output

Genome

Transcriptome

Proteome

What is the DNA sequence?

Which genes are active?

Which proteins are present?

Proteome

mass spectrometry of peptides array-based techniques

HOW?

presence of peptides & proteins abundance of peptides & proteins

WHAT?

Genome

Transcriptome

Proteome

Metabolome

What is the DNA sequence?

Which genes are active?

Which proteins are present?

Which metabolites can be identified?

Metabolome

mass spectrometry NMR spectroscopy

HOW?

presence of metabolites abundance of metabolites

WHAT?

Genome

Transcriptome

Proteome

Metabolome

What is the DNA sequence?

Which genes are active?

Which proteins are present?

Which metabolites can be identified?

Interactome Which molecules are interacting?

Interactome

mass spectrometry, yeast-2-hybrid text mining

HOW?

links between moleculesWHAT?

Genome

Epigenome

Transcriptome

Proteome

Metabolome

What is the DNA sequence?

Which genes are active?

Which proteins are present?

Which metabolites can be identified?

How are DNA and associated proteins modified?

Interactome Which molecules are interacting?

Epigenome

ChIP-seq, ChIP-chip (histones modifications) bisulfite sequencing (DNA methylation)

HOW?

histone modifications along genome DNA methylation patterns along genome

WHAT?

http://epigenomegateway.wustl.edu/browser/

http://compbio.med.harvard.edu/flychromatin/

http://compbio.med.harvard.edu/flychromatin/

Genome

Epigenome

Transcriptome

Proteome

Metabolome

Nucleome

What is the DNA sequence?

Which genes are active?

Which proteins are present?

How is the DNA organized in space/time?

Which metabolites can be identified?

How are DNA and associated proteins modified?

Interactome Which molecules are interacting?

Nucleome

3C/4C/5C chromosome conformation capture Hi-C sequencing

HOW?

contact probabilities for different parts of the genome

WHAT?

Lieberman-Aiden et al., Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome, 2009

Scaling

Dimensions

Genomic Entities

Samples

Timepoints

Data Types

?

TCGAThe Cancer Genome Atlas

mRNA expression

microRNA expression

DNA methylation

protein expression

copy number variants

mutation calls

clinical parameters

Stratome

Anthony92931 / Wikimedia Commons + Modification by Nils Gehlenborg

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)

Is there a mutation that overlaps with this mRNA cluster?

Is there a CNV that affects survival?

Is there a pathway that is enriched in this cluster?

Is there a mutually exclusive mutation?

Query

Rank

VisualizeStratifications

Clinical Params Pathways

Guided Exploration

dem

and

products

use

rs

visualization tools

use

rs

visualization tools

use

rs

visualization tools

genome browser network viewer heatmap visualization

http://genome.ucsc.org

use

rs

visualization tools

genome browser network viewer heatmap visualization

use

rs

visualization tools

customized tools for very specific problems

Meyer et al., “MulteeSum: A Tool for Comparative Spatial and Temporal Gene Expression Data”, 2010

use

rs

visualization tools

customized tools for very specific problems

What am I doing?

Building infrastructure to build visualization tools.

Data Management

Visualization Components

Visualization Tools

Data Analytics

Visualization Libraries

Data Management

Visualization Components

Visualization Tools

Data Analytics

Visualization Libraries

Abstraction

System/Platform

Data Management

Visualization Components

Visualization Tools

Data Analytics

Visualization Libraries

Abstraction

Think about scale.

Think about systems.

MD Anderson Cancer Center

University of Rostock

Psalm Haseley, Richard Park, Peter J Park

Michael S Noble, Douglas Voet, Lihua Zou, Spring Liu, Hailei Zhang, Sachet Shukla, Aaron McKenna, Andrew Cherniak, Pei Lin, Gad Getz

Jianhua Zhang, Terrence Wu, Ian Watson, Steven Quayle, Lynda Chin

Harvard Medical School

Broad Institute of MIT & Harvard

Christian Partl, Dieter SchmalstiegGraz University of Technology

Johannes Kepler University Linz Samuel Gratzl, Stefan Luger, Marc Streit

Hans-Jörg Schulz

Acknowledgements

Harvard SEAS Alexander Lex, Hanspeter Pfister

Harvard School of Public Health

Funding NIH/NHGRI K99 HG007583

Ilya Sytchev, Shannan Ho Sui, Winston Hide