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1PrognoChip Mediator, FORTH-ICS
Integrating Clinical and Genomic Information through the PrognoChip Mediator
Implemented byManos 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 DoctorsElias Sanidas, Efstathios Stathopoulos, Maria Kafousi
Medical School, University of Crete, Greece
Stamatis VassilarosProlipsis Diagnostic Breast Center, Athens, Greece
2PrognoChip Mediator, FORTH-ICS
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
3PrognoChip Mediator, FORTH-ICS
Tumor Tissue Route
Surgery Tumor sample
liquid nitrozen
or iceHistopathologist
Sample 1
Paraffin cuts
Microscope
paraffin
coloring
report
biopsis
PAGNH: University Hospital
PROLIPSIS: Breast Cancer Center
Sample 2
Tissue Bank
Microarray experiment
RNA later
extraction
FORTH-IMBB: Molecular Biology Lab
4PrognoChip Mediator, FORTH-ICS
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.
5PrognoChip Mediator, FORTH-ICS
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
6PrognoChip Mediator, FORTH-ICS
Mediator
FindingsRepository
Clinical IS
Data MiningTools
Query Engine
metadata
findings
Submit/search/update
medical doctor
(web-based) Genomic IS
NormalizationPlug-ins
Submit/search/update
biologist
(client-serverbased)
GO database
biomedical investigator
(web-based)
Visualization Tools
virtual query
Specify parameters
(local access) output XML file
store/query findings
localinstallation
store administration & temporary data Mediator
DB
PrognoChip: The Integrated Clinico-Genomics Environment
7PrognoChip Mediator, FORTH-ICS
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).
8PrognoChip Mediator, FORTH-ICS
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
20PrognoChip Mediator, FORTH-ICS
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.)
26PrognoChip Mediator, FORTH-ICS
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
30PrognoChip Mediator, FORTH-ICS
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.
35PrognoChip Mediator, FORTH-ICS
Query Processing
1. When a Query Form is saved, part of the related subquery is formed.
2. When the Select Page is filled out, final clinical subqueries are formed.
3. Clinical subqueries are submitted to Clinical IS and results are composed.
4. Based on the tumor names returned in 3), final genomic queries are formed and submitted to Genomic IS.
5. Results from Clinical IS and Genomic IS are joined based on tumor name.
6. Output XML file is formed, based on a predetermined schema.
36PrognoChip Mediator, FORTH-ICS
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
37PrognoChip Mediator, FORTH-ICS
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.
40PrognoChip Mediator, FORTH-ICS
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.
41PrognoChip Mediator, FORTH-ICS
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
42PrognoChip Mediator, FORTH-ICS
PrognoChip Mediator Web Site
http://www.ics.forth.gr/isl/projects/PrognoChip/
43PrognoChip Mediator, FORTH-ICS
Acknowledgements
The development of PrognoChip Mediator was supported by National funds within the context of:
the PrognoChip project (GSRT-EPAN).
PrognoChipPrognoChip
2004-2007