Transcript ppt presentation

Integrating Clinical and Genomic Information
through the PrognoChip Mediator
Implemented by
Manos Kalaitzakis, Dimitris Manakanatas, Haridimos Kondylakis,
Manolis Nikoloudakis, and Maria Michou
Under the guidance of
Anastasia Analyti & Dimitris Plexousakis
Institute of Computer Science, FORTH-ICS, Greece
Department of Computer Science, University of Crete, Greece
Medical Doctors
Elias Sanidas, Efstathios Stathopoulos, Maria Kafousi
Medical School, University of Crete, Greece
Stamatis Vassilaros
Prolipsis Diagnostic Breast Center, Athens, Greece
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The aim of PrognoChip is:
– the identification of molecular markers for the
classification and prognosis of Breast Cancer,
based on:
the correlation of patient’s clinicohistopathological
parameters and therapy response with their tumor
gene expression profiles
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Tumor Tissue Route
liquid nitrozen
Surgery
or ice
Tumor sample
Histopathologist
PAGNH: University
Hospital
Sample 1
PROLIPSIS: Breast
Cancer Center
paraffin
Paraffin cuts
coloring
Microscope
Sample 2
RNA later
Tissue Bank
extraction
Microarray
experiment
biopsis
report
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FORTH-IMBB: Molecular
Biology Lab
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The Integrated Clinico-Genomics Environment of
PrognoChip
Consists of:
(a)
a Clinical Information System to keep patient clinical information (i.e.,
clinical, laboratory, and histopathological information),
(b)
a Genomic Information System to manage DNA microarray
experiments, analyze raw hybridization data, and store gene expression
profiles,
(c)
a middleware layer, called PrognoChip Mediator, for the integration
of the Clinical and Genomic Information Systems, and
(d)
a Data Mining layer, for the intelligent processing of the retrieved
clinico-genomic data, knowledge extraction, and visualization.
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Three Databases to Integrate
 Genomic Information System (extension of BASE v1.2.16,
developed by Lund Univ.)
• microarray design, samples, hybridizations, etc.
 Clinical Information System (extension of Integrated Care
Solutions, developed by FORTH-ICS.)
• patient medical history, current findings, diagnostic test
results, tumor histopathologic diagnosis, etc.
 Gene Ontology (GO) Database
• ontology terms for the annotation of gene products
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PrognoChip: The Integrated
Clinico-Genomics Environment
findings
Visualization
Tools
metadata
store/query findings
Findings
Repository
Data Mining
Tools
biomedical
investigator
output XML file
virtual query
(web-based)
medical
doctor
Query
Engine
store administration
& temporary data
Mediator
Mediator
DB
biologist
Submit/search/
update
(client-server
based)
Submit/search/
update
Clinical IS
(web-based)
Genomic IS
GO database
local
installation
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Normalization
Plug-ins
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The PrognoChip Mediator
 The authorized biomedical investigator can form clinico-genomic
queries through a web-based graphical user interface.
 Specifically, the user can specify criteria for selecting tumors:
(i) excised from patients with a clinical profile of interest,
(ii) having histopathologic characteristics of interest, and
(iii) participating in a PrognoChip microarray experiment of
specified quality and characteristics.
 Returned tumors are accompanied with desirable clinico-genomic
information (e.g., gene expression profiles).
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Clinical Criteria
• Patient past breast diseases
• Gynecological history (e.g. age of menarche,
menopausal status, etc.)
• Total duration of hormone intake
• Other risk factors (e.g. smoking habits, etc. )
• Family history of malignancy
• Current findings and blood tumor markers
• Therapies before and after surgery
• Effectiveness of therapies
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Clinical Query Forms
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Tumor Histopathologic Criteria
• Tumor histological type
• Diameter
• Grade
• Lymphatic, Veinous, Perineural, Skin, Nipple, and
Lymph node invasion
• Histological TMN
• Immunohistochemical tumor markers
(ER, HER-2, etc.)
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Histopathologic Query Forms
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Genomic Criteria




The channel of the cancerous tissue
Hybridization quality indicators
Dates of hybridizations
The name of the desired normalization procedure
 Reporter/Gene filtering criteria
– GO annotations and evidence code
• Molecular Function, Biological Process, and
Cellular Location ontology terms
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Genomic Query Forms
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Select Page
After patient/tumor criteria specification, the user
selects the clinical, histopathologic, and genomic
fields of interest that will accompany the cancerous
sample in the output.
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Select Page: Part 1
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Select Page: Part 2
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Query Processing
1.
2.
3.
4.
5.
6.
When a Query Form is saved, part of the related subquery is
formed.
When the Select Page is filled out, final clinical subqueries
are formed.
Clinical subqueries are submitted to Clinical IS and results
are composed.
Based on the tumor names returned in 3), final genomic
queries are formed and submitted to Genomic IS.
Results from Clinical IS and Genomic IS are joined based
on tumor name.
Output XML file is formed, based on a predetermined
schema.
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Output XML File Schema
• For the full Output XML File schema, see:
http://www.ics.forth.gr/~analyti/PrognoChip/
OutputXMLFileSchema.jpg
• Description is provided in:
http://www.ics.forth.gr/~analyti/PrognoChip/
OutputXMLFileDescription.pdf
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Result Page
In the Result Page, the user can:
• download the complete set of output files to
his/her machine,
• view the output XML file, and
• download previous results.
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Output XML File
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Data Mining Layer
 It supports decision making operations, on
output XML files.
 Examples:
• Retrieve the tumor gene expression profiles of patients that
meet clinical profile A and clinical profile B. Then, find the
genes that best discriminate between these two groups.
• Cluster patients based on their tumor gene expression
profiles. Then, identify indicative patient clinical profiles,
for these clusters.
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Details on the PrognoChip Mediator can be
found in:
 Anastasia Analyti, Haridimos Kondylakis, Dimitris
Manakanatas, Manos Kalaitzakis, Dimitris Plexousakis,
George Potamias, Integrating Clinical and Genomic
Information through the PrognoChip Mediator, Procs. of
the 7th International Symposium on Biological and
Medical Data Analysis (ISBMDA-2006), 250-261, 2006.
Springer-Verlag
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PrognoChip Mediator Web Site
 http://www.ics.forth.gr/isl/projects/PrognoChip/
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Acknowledgements
The development of PrognoChip Mediator was
supported by National funds within the context of:
 the PrognoChip project (GSRT-EPAN).
PrognoChip
2004-2007
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Thank you !!!
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