prognochip mediator, forth-ics 1 integrating clinical and genomic information through the prognochip...

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


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


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


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.


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


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


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).


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


Clinical Query Forms


10 11


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.)


Histopathologic Query Forms


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


Genomic Query Forms


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.


Select Page: Part 1


Select Page: Part 2


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.


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


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.


Output XML File


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.


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


PrognoChip Mediator Web Site

http://www.ics.forth.gr/isl/projects/PrognoChip/


Acknowledgements

The development of PrognoChip Mediator was supported by National funds within the context of:

the PrognoChip project (GSRT-EPAN).

PrognoChipPrognoChip

2004-2007


Thank you !!!

prognochip mediator, forth-ics 1 integrating clinical and genomic information through the prognochip...

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