Cancer Informatics
18th June, 2014
Ansuman Chattopadhyay, PhD
Head, Molecular Biology Information Services
Health Sciences Library System
University of Pittsburgh
ansuman@pitt.edu
http://www.hsls.pitt.edu/molbio
Cancer Biology
Genetic alterations: Genomics
Gene expression : Transcriptomics
Clinical outcome: Drug-Gene Interactions
http://www.hsls.pitt.edu/guides/genetics
Topics
Cancer Genome Projects
Database Search
Cancer Genes
Cancer Mutations
Gene Expressions in Cancer Tissues
Compound–target interactions
Data Analysis
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
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
International Cancer Genome Consortium
(ICGC)
NCI Cancer Genome Atlas (TCGA)
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
http://circos.ca/
http://www.hsls.pitt.edu/guides/genetics
CirCos Online
Cancer Genes
Literature Search for Cancer Genes
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
$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
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
http://www.sciencemag.org/content/suppl/201
3/03/27/339.6127.1546.DC1/1235122Tables
S1-4.xlsx
Cancer Mutations
Somatic Mutations in Cancer
COSMIC
http://www.sanger.ac.uk/genetics/CGP/cosmic/
http://www.hsls.pitt.edu/guides/genetics
Cancer Mutation
Query….
a single gene
a cancer tissue
Cancer Genes
Driver
Mut-Driver
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
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:
COSMIC
ICGC Data Portal
cBIO Cancer Genomics Portal
Cancel Cell Line Encyclopedia
Intogene
ICGC Data Poertal
ICGC Search Examples
Organ/Tissue (Lung, Breast)
Projects (TCGA)
Donors/Patients
Mutations
Genes
ICGC
BRAF missense mutations in colorectal
cancer
Most frequently mutated genes in stage III
malignant lymphoma
Brain cancer donors with frameshift
mutations and having methylation data
available
Cancer Cell Line Encyclopedia
Hands-on Exercise
Start with your favorite gene or EGFR or
IDH1 and look for the presence of somatic
mutations in cancer tissues.
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
TTN
Olfactory Genes
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
NCBI Cancer Chromosome
http://www.ncbi.nlm.nih.gov/sites/entrez?db=cancerchromosomes
NCBI SKY/M-FISH CGH Database
NCI Recurrent Aberration in Cancer
http://www.ncbi.nlm.nih.gov/projects/sky/skyquery.cgi
http://cgap.nci.nih.gov/Chromosomes/RecurrentAberrations
ChimerDB 2.0
http://ercsb.ewha.ac.kr:8080/FusionGene/
http://www.hsls.pitt.edu/guides/genetics
Cancer Transcriptome
Cancer Microarray Database
NCBI Gene Expression Omnibus
EBI Array Express
http://www.ncbi.nlm.nih.gov/geo/
http://www.ebi.ac.uk/microarray-as/ae/
NextBio
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
Cancer Resource:
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
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
http://www.nature.com/tcga/
Pan-Cancer Analysis
Pan-Cancer Analysis
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
Search and Explore
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
ansuman@pitt.edu
412-648-1297
@ansuman90
