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Systems Networks and Cancer Sharmila Bapat, Ph.D National Centre
for Cell Science, Pune, [email protected] Africa-India
Joint Virtual Conference 2011
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EnvironmentMolecular Pathways &
NetworksCellsTissuesIndividualsBasic Life
ProcessesHomeostasisGenetic CompositionEpigenetic RegulationBifx
Africa-India Joint Virtual Conference 2011
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Digitalization of the human genome ChromatinChromosomesGenes
(DNA)RNAProteins
NetworksCellsTissuesIndividualsEnvironmentBifx Africa-India
Joint Virtual Conference 2011
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Imbalance in such profiles that constitute networks leads to
aberrant states
such as cancer
in which cell, tissue and functioning are compromised.Bifx
Africa-India Joint Virtual Conference 2011
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It thus becomes pertinent to question cancer as an aberrant
state defined
by disrupted networks in the transformed cell / tissue
i.e.
Resolve the transformed state as a function of systems networks
rather
than address it on a reductionist level as being driven by a
single geneBifx Africa-India Joint Virtual Conference 2011
-
Systems Biology
Hypothesis-driven
Global data acquisition
Integrate data from different platforms/diff types of data
Delineate biological network dynamics
Formulate models that can be validatedApplying the principles of
systems biologyBifx Africa-India Joint Virtual Conference 2011
-
An example in point studied recently in our lab is that of
the identification of a gene signature associated with
serous ovarian adenocarcinoma Bifx Africa-India Joint Virtual
Conference 2011
-
Serous ovarian adenocarcinoma is one of the most aggressive
Gynecological cancers and is associated with a
very poor prognosis for most patients
It is often termed as Silent Killer because of lack of early
symptoms of
disease and rapid progression to a metastatic stage Bifx
Africa-India Joint Virtual Conference 2011
-
Poor correlation in biomarkers identified betweenprevious
studies
- Limited sample size - Limited normal tissue primary
Vs.metastases - Discrepancy across microarray platforms - Limited
validationIntegrative Approaches for the identification and
assessment of Cancer BiomarkersBifx Africa-India Joint Virtual
Conference 2011
-
1. A4 in vitro model transformation systemDifferential Gene
Expression Databases for serous ovarian carcinomas 2. IST - In
Silico Transcriptomics3. TCGA -The Cancer Genome
AtlasIdentification of a SeOvCa gene signature based on
transcriptional profilingBifx Africa-India Joint Virtual Conference
2011
-
Analytical Pipeline
-
SeOvCa gene
signatureCDCA4EXO1LAMA5MALMCM2MESTMMP9RRM2SLC39A4SOX17SYNCRIPTM7SF2TNNT1DAB2DIXDC1EFEMP1FBN1GNB5HNMTKLF2LHFPLRRC17PAPSS2PROS1PTGISRNASE4SGK1SMARCA2ATAD2Downregulated
genesBCAT1Bifx Africa-India Joint Virtual Conference 2011
-
In silico validation with the database Prognoscan-1+2Bifx
Africa-India Joint Virtual Conference 2011
-
Algorithm for the Reconstruction of Accurate Cellular
NetworksSystems Networks Analysis Applying ARACNe 30 SeOvCa
signature genes were considered as nodes around which interactions
were predicted as individual or interacting hubs.
The MI (Mututal Information) was fixed at 0.20
DPI (Data Processing Inequality) was set at 0.10. Bifx
Africa-India Joint Virtual Conference 2011
-
Node - Interacting Genes Network (27-781) Stand-alone
NodesSocial NodesBifx Africa-India Joint Virtual Conference
2011
-
Node - Linker - Node Interactions (23 nodes 95 linkers)Bifx
Africa-India Joint Virtual Conference 2011
-
Components of the Interface Network (20 nodes 9 linkers)Bifx
Africa-India Joint Virtual Conference 2011
-
Chromosomal location analyses of the networkNode-gene same
chromosome location
-
Predictions of copy no. amplifications6q12 -
6q16.16q218q24.320q11.2-20q13.3SYNCRIPATAD2SLC39A4LAMA5Bifx
Africa-India Joint Virtual Conference 2011
-
6q21 /8q24.320qValidation - FISHBifx Africa-India Joint Virtual
Conference 2011
-
MALMESTEFEMP1PAPSS2PTGISFBN1ELELELELELH3K9H3K27H3K4INPUTAb
CTRLPTGISMALMEST-4723-4673-4592-4542-3523-3473369413499455-122-930-866-405-349-251-171-107-6390134A2A1A2A1PAPSS2EFEMP1FBN1-3003-2951-203-159-77-1522-1244-1478-1200-1122-1077-233-189A1A1A1A1HypomethylationNo
change in methylation
K4K27K4-K9K4-K27K9-K27K4-K9-K27TSSDOWNEpigenetic Regulation of some
SeOvCa genesBifx Africa-India Joint Virtual Conference 2011
-
Protein Interaction Networks (PINA)Bifx Africa-India Joint
Virtual Conference 2011
-
Overlap of ARACNe and PINA NetworksBifx Africa-India Joint
Virtual Conference 2011
-
c-MYCp53Rb1Gene and Protein NetworksBifx Africa-India Joint
Virtual Conference 2011
-
Identification of functional modules in serous ovarian
adenocarcinomaBifx Africa-India Joint Virtual Conference 2011
-
Sharmila A. Bapat, Anagha Krishnan, Avinash D. Ghanate, Anjali
P. Kusumbeand Rajkumar S. Kalra -
Gene Expression: Protein Interaction Systems Network Modeling
Identifies
Transformation-Associated Molecules and Pathways in Ovarian
Cancer
Cancer Research 70(12); 480919 2010References for this
presentation cited in the following publication
-
AcknowledgementsCollaborators
Dr. C.B.Koppiker, Jehangir Hospital, PuneDr. Matthias Nees, VTT,
Turku, FinlandDr. Renu Wadhwa, AIST JapanDr. Sunil Kaul, AIST
JapanFunding
Department of Biotechnology, Ministry of Science &
Technology, Govt. of IndiaMr. Avinash MaliMs. Anjali KusumbeMr.
Rajkumar Kalra Mr. Brijesh KumarMr. Anand Kamal SinghMs. Rutika
NaikMs. Rohini KshirsagarMs. Tejaswini DeshpandeMr. Swapnil
KambleMr. Nilesh GardeDr. Nicholas BerryDr. Nawneet KurreyDr. Neeti
SharmaMs. Swati JalgaonkarMs. Shweta JadhavMs. Nimisha SinghMr.
Avinash GhanateMs. Anagha KrishnanMr. Prasad ChaskarMr. Mihir
MetkarMs. Divya RamalingamMr. Alok JoglekarAlumniResearch
group@NCCS
