Transcript Cancer Informatics - University of Pittsburgh

Cancer Informatics
18th June, 2014
Ansuman Chattopadhyay, PhD
Head, Molecular Biology Information Services
Health Sciences Library System
University of Pittsburgh
[email protected]
http://www.hsls.pitt.edu/molbio
Cancer Biology
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Genetic alterations: Genomics
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Gene expression : Transcriptomics
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Clinical outcome: Drug-Gene Interactions
http://www.hsls.pitt.edu/guides/genetics
Topics
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Cancer Genome Projects
Database Search
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Cancer Genes
Cancer Mutations
Gene Expressions in Cancer Tissues
Compound–target interactions
Data Analysis
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Ingenuity Pathway Analysis
NextBio Research Premium
http://www.hsls.pitt.edu/guides/genetics
Notable Talks / Articles
Talk -- Cancer Genomics: Fulfilling the
Promise
http://www.youtube.com/watch?v=gGdcgUub6YQ
Garraway, Levi A., and Eric S. Lander.
"Lessons from the cancer genome." Cell153.1 (2013): 17-37.
http://www.sciencedirect.com/science/article/pii/S0092867413002882
TCGA Symposium
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http://www.youtube.com/playlist?list=PL1ay9ko4A8sk4l9pbggl5A7T
U4BxAstG3
Excellent Review
Vogelstein, Bert, et al. "Cancer genome
landscapes." science 339.6127 (2013): 15461558.
http://goo.gl/byrkQY
Henry Stewart Talks
http://hstalks.com.pitt.idm.oclc.org/main/browse_series.php?j=764&c=252
Introduction
Henry Stewarts Talk
http://hstalks.com.pitt.idm.oclc.org/main/view_talk.php?t=154&r=20&c=252
Cancer Stem Cell
Cancer: Clonal evolution
Greaves, M. (2007), "A Darwinian Eye View of Cancer", in Nesse, R. (ed.), Evolution and Medicine: How New Applications Advance Research
and Practice, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/bio)
http://www.hsls.pitt.edu/guides/genetics
The lineage of mitotic cell divisions from the fertilized egg to a
single cell within a cancer showing the timing of the somatic mutations
acquired by the cancer cell and the processes that contribute to them.
MR Stratton et al. Nature 458, 719-724 (2009) doi:10.1038/nature07943
Fig. 2 Genetic alterations and the progression of colorectal cancer.
Fig. 2 Genetic alterations and the
progression of colorectal cancer.
B Vogelstein et al. Science 2013;339:1546-1558
B Vogelstein et al. Science 2013;339:1546-1558
Published by AAAS
DNA Sequencing Cost
http://www.genome.gov/sequencingcosts/
http://www.hsls.pitt.edu/molbio
Cancer Genome Projects
http://www.hsls.pitt.edu/guides/genetics
Cancer Genome Projects
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International Cancer Genome Consortium
(ICGC)
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NCI Cancer Genome Atlas (TCGA)
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The Sanger Institute Cancer Genome
Projects
http://www.hsls.pitt.edu/guides/genetics
The Cancer Genome Atlas (TCGA)
URL:
http://cancergenome.nih.gov/
Goal:
Cancer Type: 20
Sample: 500 / cancer type
http://www.hsls.pitt.edu/guides/genetics
The Cancer Genome Projects
http://www.hsls.pitt.edu/guides/genetics
The International Cancer Genome
Consortium
http://www.hsls.pitt.edu/guides/genetics
Cancer Genome
Leidford etal. Nature 464,(2010)
http://www.hsls.pitt.edu/guides/genetics
Cancer Genome
Leidford etal. Nature 464,(2010)
http://www.hsls.pitt.edu/guides/genetics
Circos Plot
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http://circos.ca/
http://www.hsls.pitt.edu/guides/genetics
CirCos Online
Cancer Genes
Literature Search for Cancer Genes
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NCBI Gene : http://www.ncbi.nlm.nih.gov/gene
Quertle: http://www.quertle.info/
BioBase: https://portal.biobase-international.com/cgi-bin/portal/login.cgi
DigSeE: http://210.107.182.61/geneSearch/
Literature Search Engine
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$Genes for Cancer
$Genes Thyroid Cancer
$Neoplasms IDH1
TP53 over-expressed in what $Neoplasms?
What $Drugs target BRAF?
Quertle Search
List of Articles
List of …
Genes
$Genes
Disease States
$Diseases
Drugs
$Drugs
DigSee : Disese Gene Search Engine
http://210.107.182.61/geneSearch/
Cancer Genes Catalogs
http://www.hsls.pitt.edu/guides/genetics
Cancer Gene Census
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http://www.sanger.ac.uk/genetics/CGP/Census/
http://www.hsls.pitt.edu/guides/genetics
Cancer Gene Census
Catalog of Cancer Genes
http://www.sciencemag.org/content/339/6127/1546.full
Catalog of Cancer Genes
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http://www.sciencemag.org/content/suppl/201
3/03/27/339.6127.1546.DC1/1235122Tables
S1-4.xlsx
Cancer Mutations
Somatic Mutations in Cancer
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COSMIC
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http://www.sanger.ac.uk/genetics/CGP/cosmic/
http://www.hsls.pitt.edu/guides/genetics
Cancer Mutation
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Query….
a single gene
 a cancer tissue
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Cancer Genes
 Driver
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Mut-Driver
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Oncogene
Tumor Suppressor
Epi-Driver
Passenger
Driver Mutations
Fig. 4 Distribution of mutations in two oncogenes (PIK3CA and IDH1) and two tumor
Oncogene and Tumor Supressor Genesuppressor genes (RB1 and VHL).
20/20 Rule
B Vogelstein et al. Science 2013;339:1546-1558
Published by AAAS
Common Questions
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Is my favorite gene frequently mutated in
colon cancer?
Which genes are reported to be mutated in
liver cancer?
Are the mutations in my favorite gene
“drivers” in a specified tumor type?
Which genes are known to be mutated in
A549 cell line?
http://www.hsls.pitt.edu/guides/genetics
Cancer Genomics databases:
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COSMIC
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ICGC Data Portal
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cBIO Cancer Genomics Portal
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Cancel Cell Line Encyclopedia
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Intogene
ICGC Data Poertal
ICGC Search Examples
Organ/Tissue (Lung, Breast)
Projects (TCGA)
Donors/Patients
Mutations
Genes
ICGC
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BRAF missense mutations in colorectal
cancer
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Most frequently mutated genes in stage III
malignant lymphoma
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Brain cancer donors with frameshift
mutations and having methylation data
available
Cancer Cell Line Encyclopedia
Hands-on Exercise
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Start with your favorite gene or EGFR or
IDH1 and look for the presence of somatic
mutations in cancer tissues.
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Start with your cancer of interest and retrieve
associated genes with somatic mutations
http://www.hsls.pitt.edu/guides/genetics
Driver Vs. Passenger Mutations
Replication Timing; Mutation Frequency
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TTN
Olfactory Genes
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Animation:
http://en.wikipedia.org/wiki/File:Animatedfiringprog
ress.gif
Nature paper:
Lawrence, Michael S, Petar Stojanov, Paz Polak, Gregory V Kryukov, Kristian
Cibulskis, Andrey Sivachenko, Scott L Carter, et al. 2013. “Mutational
Heterogeneity in Cancer and the Search for New Cancer-Associated Genes.”
Nature 499 (7457) (July 11): 214–8. doi:10.1038/nature12213.
http://dx.doi.org/10.1038/nature12213.
Cancer Driver Genes
Cancer Mutation
Fig. 8 Signal transduction pathways affected by mutations in human cancer.
B Vogelstein et al. Science 2013;339:1546-1558
Published by AAAS
Spectral karyotype
The diploid genome sequence of an individual human. PLoS Biol. 2007 Sep 4
http://www.hsls.pitt.edu/guides/genetics
Chromosome
Aberrations/Translocations
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NCBI Cancer Chromosome
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http://www.ncbi.nlm.nih.gov/sites/entrez?db=cancerchromosomes
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NCBI SKY/M-FISH CGH Database
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NCI Recurrent Aberration in Cancer
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http://www.ncbi.nlm.nih.gov/projects/sky/skyquery.cgi
http://cgap.nci.nih.gov/Chromosomes/RecurrentAberrations
ChimerDB 2.0
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http://ercsb.ewha.ac.kr:8080/FusionGene/
http://www.hsls.pitt.edu/guides/genetics
Cancer Transcriptome
Cancer Microarray Database
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NCBI Gene Expression Omnibus
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EBI Array Express
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http://www.ncbi.nlm.nih.gov/geo/
http://www.ebi.ac.uk/microarray-as/ae/
NextBio
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https://hsls.nextbio.com/
http://www.hsls.pitt.edu/guides/genetics
Gene Expression Databases
NCBI
• Gene Expression Omnibus
(GEO)
EBI
• ArrayExpress
http://www.hsls.pitt.edu/guides/genetics
Array Express
http://www.hsls.pitt.edu/guides/genetics
Gene Expression Atlas
http://www.ebi.ac.uk/gxa/
http://www.hsls.pitt.edu/guides/genetics
NextBio
https://hsls.nextbio.com
http://www.hsls.pitt.edu/guides/genetics
NextBio
NextBio
NextBio
Cancer Pathways
Fig. 8 Signal transduction pathways affected by mutations in human cancer.
B Vogelstein et al. Science 2013;339:1546-1558
Published by AAAS
Fig. 7 Cancer cell signaling pathways and the cellular processes they regulate.
B Vogelstein et al. Science 2013;339:1546-1558
Published by AAAS
Common Pathways: IPA
http://www.hsls.pitt.edu/guides/genetics
Pathway Map: p53
Red:
Green:
http://www.hsls.pitt.edu/guides/genetics
Pathway Drawing Tool : ePath3D
http://hsls.libguides.com/molbio/epath3d
ePath3D online
Cancer Drugs
http://www.hsls.pitt.edu/guides/genetics
Compound Target Interactions
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Cancer Resource:
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http://bioinformatics.charite.de/cancerresource/
http://www.hsls.pitt.edu/guides/genetics
Cancer Resources
http://www.hsls.pitt.edu/guides/genetics
Cancer Resources
http://www.hsls.pitt.edu/guides/genetics
Compound Target Interactions
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http://www.cancerrxgene.org/
http://www.hsls.pitt.edu/guides/genetics
Compound Target Interactions
http://www.hsls.pitt.edu/guides/genetics
Personalized Cancer Medicine Portal
http://goo.gl/HCvbd
Pan Cancer Analysis
TCGA Pan-Cancer Data
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http://www.nature.com/tcga/
Pan-Cancer Analysis
Pan-Cancer Analysis
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http://www.nature.com/ng/journal/v45/n10/full/ng.2762.html
Tumor classification
Oncogenic Signature
Gene Expression Data
Analysis
Microarray Data Analysis
raw
data
GeneSpring / Partek
Statistical packages
Gene List
Literature findings
Biology
•Ingenuity IPA
•GeneGO Metacore
•DAVID
•Explain
http://www.hsls.pitt.edu/guides/genetics
Pathway Analysis
Control
Treated
A549 cell
+
Ethanol (25mmol/L) 48 hr
A549 cell
+
Resveratrol (25mmol/L) 48 hr
YouTube video on Resveratrol
http://www.hsls.pitt.edu/guides/genetics
Gene Expression Databases
NCBI
• Gene Expression Omnibus
(GEO)
EBI
• ArrayExpress
http://www.hsls.pitt.edu/guides/genetics
Microarray Data Processing: ArrayAssist
Workflow:
http://www.hsls.pitt.edu/guides/genetics
Microarray Processed Data
http://www.hsls.pitt.edu/guides/genetics
Discovery Step: Pathway Analysis
Ingenuity
IPA
DAVID
Gene List
http://www.hsls.pitt.edu/guides/genetics
Metacore
Ingenuity IPA
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Search and Explore
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Genes, proteins, diseases and chemicals
Connect genes
Build pathways
Explore pathways
Analyze dataset
Interpret high-throughput data in the context of biological
processes, pathways and networks
http://www.hsls.pitt.edu/guides/genetics
Common Functions and Pathways: IPA
Analysis
http://www.hsls.pitt.edu/guides/genetics
Common Pathways: IPA
http://www.hsls.pitt.edu/guides/genetics
Pathway Map: p53
Red:
Green:
http://www.hsls.pitt.edu/guides/genetics
Pathway Map: NFkB and TGF beta
http://www.hsls.pitt.edu/guides/genetics
Interaction Network Maps: IPA
http://www.hsls.pitt.edu/guides/genetics
Interaction Map with Data Overlay: IPA
http://www.hsls.pitt.edu/guides/genetics
Search Engine for Cancer Resources
Thank you!
Any questions?
Ansuman Chattopadhyay
[email protected]
412-648-1297
@ansuman90