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L. J. Morris1,2, J. D. Brenton1,2, C. Caldas1,2, J. Davies3, S. Harris3, I. Papatheodorou1,2, P. Maccallum2, C. Crichton3,
1Department
of Oncology, University of Cambridge, Cambridge, UK; 2CRUK-Cambridge Research Institute, Cambridge, UK
3Computing Laboratory, University of Oxford, Cambridge, UK
Tissue microarray repository
Introduction
Expression microarray analysis has resulted in the
discovery of many novel gene signatures that are
correlated with clinical outcomes in cancer
treatment. Tissue microarrays (TMAs) from paraffinembedded tumour samples are an ideal reagent for
validation of these potential biomarkers, prior to their
clinical use. In the CancerGrid project, we have been
working on techniques for the automatic integration of
TMA data with clinical data obtained in large phase III
studies. This poster describes the tracking and
exchange of TMA data between different institutions
involved in running a phase III study in breast cancer.
•
Acts as a hub to exchange data between collaborators
•
Prepares and exports the data in a format ready for
statistical analysis and integration with clinical data-sets
•
Stores XML slidemap files (provides positional data for
Genentix Ariol Slide Scanner)
•
Stores the results of automated image analysis from Ariol
and manual analysis from pathologist scoring
Cambridge
University
Tissue microarray standards
We looked at the required Common Data Elements
(CDEs) to describe the data exchanged between 2
laboratories involved in running TMA analysis for
several large trials
IIS
TMA images
and metadata
Java Client
slidemap
• define data for exchange
Excel Map.xml
• make use of existing TMA standards (e.g. API Data
Exchange Specification, slidemap schema for TMA
layout developed by the Sanger Centre)
• review CDEs with pathologists and researchers
involved in all stages of TMA analysis from tissue
block collection, TMA design, immunohistochemistry
and statistical analysis
Analysis results
C
Department of Astronomy
TMA designs
TMA results
Pathology data
Pathology.xml
TMA Results
Analysis Results
Images+meta-data
Figure 2 Object model showing the relationship of the TMA CDEs to each
other. Each object represents a CDE. CDEs surrounded in purple are the
terms used in a TMA design (slidemap schema). The remaining terms are
used to describe the results of a TMA experiment. The model allows the
tracking of results (i.e scores attached to a TMA Core images) back to a
patient to enable the integration of clinical data.
•
a TMA block/slide so that it could be analysed in a
different laboratory from where it was created.
•
a set of results from a TMA so they can be integrated
into external databases
Schemas annotated with CDEs, using SAWSDL references
(to appropriate CDE identifier)
Schema for slidemap TMA design
Different results schemas for different scoring systems
Figure 3. Tissue Microarray Repository (TMAR) consists of an
XML database (containing TMA designs or slidemaps, TMA results
data; and associated pathology data) and a web –based front-end
to browse the data. A web service client exports data from the Ariol
TMA SQL-Server database.
Conclusions and future work
We plan to add the ability to browse and score images via
a web-interface, to enable remote and multi-centre scoring
by pathologists. Images that are analysed externally (e.g.
for image analysis by the Department of Astronomy) are
named with tracking data, so that the image can be
uniquely identified, linked back to patient data and
compared with different types of analysis for the same
image. The SAWSDL references (to CDE identifiers)
within the XML schemas could be used to add validation,
for example check whether scores are within an accepted
range, prior to exchange of the data. The annotation of data
with CDEs allows automatic comparison and integration
of data from a variety of sources, enabling data to be reanalysed and shared amongst different researchers.
Figure 1 Screenshot from the CancerGrid Metadata Registry, showing an
example of two TMA CDEs
Acknowledgments
We thank Will Howat (Histopathology Core, CRUK-CRI) and Gareth Maslen
(Sanger Centre) for providing the slidemap schema.
TMAR
TMA Results
The set of TMA CDEs were designed to facilitate the
exchange of data and annotate:
This work was supported by…
Ariol Web
Service
Strangeways Laboratory
• define a minimum set of CDEs (figure 1 and 2)
NHS
CRUK-CRI
Literature cited
The tissue microarray data exchange specification: A community-based, open source tool for sharing tissue
microarray data BERMAN ET AL, BMC Med Inform Decis Mak. 2003; 3: 5.