The%20TMAJ%20Software%20Project%20and%20Database:

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The TMAJ Software Project and Database

• Angelo M. De Marzo MD PhD
• James Morgan BS

November 12, 2007
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Introduction

• Many putative new disease target genes with
  diagnostic, prognostic, and therapeutic
  applications
• Validation requires many samples
• Quantitative RT-PCR or protein arrays have
  disadvantages
• Genes may be expressed in multiple different cell
  types
• In situ analyses ideal but generally slow
• Tissue microarrays address some of these problems

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TMA Technology
Tissue microarray technology for high-throughput
molecular profiling of cancer Kallioniemi O
et.al. Human Molecular Genetics, 2001, vol. 10,
No. 7
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Slide from Mark A. Rubin, M.D, Dana Farber
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Donor Block Sampling
Transfer to Recipient Block
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Tissue Microarray Advantages

• High throughput
• Expands tissue use
• Uniform reaction conditions
• Built-in controls
• Economize use of reagents
• Facilitates data recording and linking to
  clinical data

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JHU Tissue Microarray 400 cores, 0.6 mm
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Tissue Microarray 400 cores, 0.6 mm each HE
of 4 µm section
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Digital Image Acquisition

• Can use conventional microscopes
• Record data in spreadsheet diagnoses and
  interpretations
• Or the data can be recorded on paper for later
  entry into a spreadsheet or database
• Major Problem
• Easy to loose track of the x and y coordinates of
  given spots

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Tissue Microarray Image Acquisition
ACIS II, DAKO
Aperio ScanScope
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Need for Data Management
200 TMAs from Johns Hopkins TMA lab
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What is TMAJ?

• TMA-J is a set of open source software tools and
  backend database structure to facilitate
  management and analysis of tissue microarrays and
  associated pathology and image data

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What Does TMAJ Do?
The software applications provide a platform for

• Entering pathology data
• Managing users and permissions
• Designing TMAs
• Viewing and scoring TMA (and other) images online
• Side-by-side viewing of serial TMA images from
  slides stained for different biomarkers
• Publishing large numbers of TMA images and
  datasets on the Internet

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What Does TMAJ Do?

• The Database Tracts
• Clinical information about patients
• Pathology specimens and associated data
• Pathology tissue blocks
• Tissue Microarray cores
• TMA Blocks
• TMA Slides
• TMA core images
• TMA image scoring data manual or semi-automated

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Primary Goals of System

• Address security issues
• Remove or isolate patient identifiers
• Manage multiple organ systems
• Develop web based interface
• Scalable to accommodate large number of
  simultaneous users
• Storage of large sets of images with diagnoses
• Data structure compatible with emerging standards
  for easy data exchange
• CaBIG compatibility (to be defined)
• The tissue microarray data exchange
  specification
• Berman et al., (http//www.pubmedcentral.nih.gov/a
  rticlerender.fcgi?artid165444)

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Database Design
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Patients, Specimens, Blocks
The Patients, Specimens, Blocks, and Tissue
Diagnosis tables all form a one-to-many
relationship.
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ArrayBlocks
The Schema of ArrayBlock-related tables. 
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Security Protecting Patient Information

• Database stored on a secure server
• Identifiable patient information in encrypted
  tables (Approved by the IRB)
• Researchers have no access to patient identifiers
• Creates virtual separate entities clinical
  database and research database

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DATA
Tissue Microarrays 701 Specimens 29,860 Tissue
Blocks 34,783 ArrayCores 90,051 ArraySlides
7532 ArrayImages 248,746
230 users, 41 Institutions, updated Nov. 4, 2008
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Specimens in TMAJ
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Tissue Blocks in TMAJ
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Applications Java from Sun Microsystems

• Java Web Start Software
• Java Web Start software provides a
  browser-independent architecture for deploying
  Java technology-based applications to the client
  desktop
• Each application runs on a dedicated Java Virtual
  Machine (JVM)

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Applications Screenshots
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Specimens Application

• This application allows for detailed input of
  data on individual specimens and
  donor-tissue-blocks. 

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Security Options Specimens

• Users may only access specimens to which they
  have permission.
• Admins may assign a user permission to a specimen
  by using the Users-Specimens tab in the
  Administrator application.

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Images Application
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Image Application Filtering

• The table shows information about every image
  (identified by x and y) in an ArraySlide.
• Images identified as Prostate Carcinoma are
  highlighted in red.

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Images Application Viewing 2 Stains
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T. Cornish, MD PhD, J. Morgan Image Analysis
Software in Process (v 1.0)
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Publishing TMA Images and Scoring Data Over the
Internet

• Roughly modeled after Stanford Microarray
  Database
• Concept
• Once a study is published by a journal, all TMA
  diagnoses, image, scoring and non-protected
  clinical data can be published as supplemental
  data to the Internet for public online viewing or
  down loading
• TMAJ Images now linked to Proteinpedia database
• (http//humanproteinpedia.org) by Akhilesh Pandy,
  MD PhD.

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For More Information

• http//tmaj.pathology.jhmi.edu
• To see published images
• login to tmaj as a guest and then click the
  Images button.
• Username guest
• Password guest

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Institutions Using TMAJ

• Johns Hopkins University
• Harvard Dana Farber Cancer Institute
• Cleveland Clinic
• University of Texas Southwestern
• Vanderbilt University

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Dynamic Fields in TMAJ

• What are Dynamic Fields, why are they important,
  and how are they managed in TMAJ?

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Dynamic Fields

• Different organ systems will have different
  recorded data. For example the Gleason score is
  only relevant to the prostate.
• Dynamic fields allow TMAJ to keep track of
  different data for different organ systems.
• TMAJ can have dynamic fields added at any time
  through the GUI. Database access is not needed
  and the code does not need to be recompiled.

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Dynamic Fields GUI
? The user is prompted to choose a specimen type.
When users add a new specimen, they are prompted
to choose a Specimen Type. In this case they
choose the Radical Prostatectomy type. After
the type is selected, we see fields that are
common for every specimen (SurgPathNumber and
Date SpecimenTaken), as well as fields that are
only relevant for a Radical Prostatectomy
(GleasonSum, HasSeminalVesicle). Note the
dynamic fields are in italics.
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Changing Meta Data
Above we see a Type called Prostate Atrophy
with several fields such as HistologicType and
Prostate_Zone. The Prostate_Zone has several
allowed choices such as Central Zone and
Peripheral Zone. These values can be added,
modified, or deleted by using the buttons on
right.
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One Approach A Key-Values Table

• A Key Values table would only have 3 fields A
  Key (such a Prostate Weight), a value, and a
  foreign key that links the record back to the
  main table (such as the Specimens table).
• We did not use this approach because it does not
  keep track of the meta-data. Meta-Data is data
  that describes data, and in this case it would be
  the type (Prostate), the field for the type
  (Prostate Weight), and any allowed choices.

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Dynamic Data for Specimens

• Fields common to all Specimens are stored in the
  Specimens Table
• The SpecimenTypes, SpecimenFields, and
  SpecimenEnums are the Meta Data
• The SpecimenTypes contains values such as
  Prostate, Bladder, Kidney, and Lung
• The SpecimenFields lists the field names for each
  Specimen Type. A Prostate SpecimenType may have
  a Gleason Score or Prostate Weight field.
• The SpecimenEnums table give a list of valid
  choices for each SpecimenField.

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TMAJ Frida Integration

• The image analysis software package Frida has
  been integrated with TMAJ

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Using Image Analysis in TMAJ

• New Image Analysis Sessions are created for a
  scanned array-slide

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Viewing Image Analysis Results

• Image Analysis Results may be viewed side-by-side
  with a regular scoring session

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Acknowledgements
Tissue Microarray Lab Marc Halushka MD
PhD Helen Fedor BS Marcella Southerland BS Qizhi
Zheng MD James Morgan BS Kristen Lecksell BS
De Marzo Lab Jessica Hicks BS Toby Cornish MD
PhD