University of Iowa Holden Comprehensive Cancer Center caBIG Proposal Overview

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University of Iowa Holden Comprehensive Cancer
CentercaBIG Proposal Overview
Holden Comprehensive Cancer Center (HCCC) George
Weiner, Director Center for Bioinformatics and
Computational Biology (CBCB) Thomas Casavant,
Director Coordinated Laboratory for Computational
Genomics (CLCG) Terry Braun, Director The
University of Iowa Iowa City, Iowa
USA. http//www.uihealthcare.com/depts/cancercente
r/ http//genome.uiowa.edu Meeting participants
Thomas Casavant, Terry Braun, Todd Scheetz,
Andrew Williams, Ramon Lawrence, Jill Kuennen,
Erin Brothers
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Iowas Trenches NCI Cancer and Bioinformatics
Centersexperiences for Community Resource
Development

• Study design assistance and execution
• Permit and promote data sharing through
  interoperability
• Resource development and integration at multiple
  sites
• Data curation and integration

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OverviewExisting Projects Integral to caBIG
Goals

• Transcript Annotation Prioritization and
  Screening System
• (TrAPSS)
• Clinical and Expression Database
• (CED)
• Integrated Expression Environment
• (IEE)
• Custom Sequence Annotation
• (CSA)
• Population Study/Disease Locus Association System
  
• (GenoMap)

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TrAPSS in a Shared Architecture Environment

• Transcript Annotation Prioritization and
  Screening System (TrAPSS)
• Accelerates mutation identification
• laboratory and data automation
• quantitative method to infer pathogenicity
• established software system with user base,
  testing, and feedback
• future development for candidate prioritization

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TrAPSS System Architecture
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PrimerViewer(A TrAPSS component)
The two highest scoring PAR regions for this gene.
Annotation
Primers
Text-based view of a gene structure.
Graphical view of a gene structure.
The PAR Graph
Gene Structure
PAR graph for this gene.
PrimerViewer is a program written to aid in the
selection of oligo pairs for mutation screening.
It also calculates PAR to prioritize regions of
importance for genes.
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Clinical and Expression Database (CED) The
Challenge

• Expression Data
• Multiple computers
• Multiple formats

• Clinical Data
• Paper records
• Electronic Documents
• e.g., pathology, histology
• Diagnoses, prognoses, etc

• Analysis
• Time consuming
• Manual operations
• Difficult to repeat
• Inaccessible to others
• Difficult for collaborators

Analysis
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CED Key Goals

• Develop extensible storage system for both
  clinical and expression data
• Accessible to lab members and collaborators
• Web-based Interface
• Secure data access
• Support multiple, diverse projects
• Allows user management
• Performs basic data analysis with extensive
  annotation
• Provides searching by clinical and expression
  parameters simultaneously

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CED Clinical and Expression Synergy

• Simultaneous analysis of data from multiple
  methods
• EST libraries
• SAGE
• Microarray
• Analysis utilizing multiple annotations
• Unigene
• LocusLink
• Gene Ontology (GO)
• Enzyme Classification (EC)
• Metabolic pathways
• Genomic location
• Allow searches for genes and tissue samples based
  on clinical and expression data
• List all grade 2 chondrosarcoma tissues where
  subject has undergone radiation therapy and p21
  expression is more than 5 different than control
  samples
• Find genes expressed at greater than 5-fold
  difference in grade 3 chondrosarcoma tissues than
  in normal cartilage tissues

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IEE - Integrated Expression Environment
Infrastructure
For large and/or heterogeneous datasets
Raw Data
Analysis Suite
File Server
Results (gene lists, graphs, etc)
link
Http Server
For small and/or homogeneous datasets
PC User
cgi
java
Web browser
GeneSpring
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IEE Web-based µ-array Design, Management, and
Analysis
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CSA Custom Sequence Annotation

• CSA Goals
• Online Access
• User-customized pipeline
• Modular components for pipeline
• Flexible design

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CSA Custom Sequence Annotation(An Illustrative
Example EST-based Gene Discovery Pipeline)
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An Integrated Bioinformatics System Design for
ExpressionCED, IEE and CSA
Clinical Database
Expression Database(s)
Analytical Tools/Database
(Hierarchy)
(Data Sources)
Expressed Sequence Tags (ESTs)
Species Subject Tissue (e.g., tumor) Tissue Sample

• Statistical Analyses
• Quality assessment
• Significance tests
• Sub-classification

Demo- graphics
Pathology Histology
Serial Analysis of Gene Expression (SAGE, MPSS)
Cell line

• Algorithmic Classification
• Pathway identification
• Annotation search
• Transcript analysis

Lab protocol and material control
Micro-arrays (cDNA, Affy, Oligo, etc)
mRNA cDNA Library
RT-PCR, QPCR, etc
Database Integration and Support for Complex
Queries
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Disease Gene Isolation GenoMap

• Driven by large collaborations
• GenoMap goals
• Web-based cooperating heterogeneous users
• Portable, intuitive interface
• Share information among multiple distributed
  clients
• Avoid replication of data to prevent coherency
  problems
• Provide security
• Fundamental Information Components Managed
• pedigree information (familial relationships)
• clinical observations of disease (phenotype)
• sets of known informative genetic probes (genetic
  markers)
• genotypes (inherited genetic patterns)

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UI-Holden ToolscaBIG Interoperability
caBIG Data
Clinical
GenoMap
Expression
CED
IEE
CSA
TrAPSS
Annotation
caBIG Data
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Iowas Trenches NCI Cancer and Bioinformatics
Centersexperiences for Community Resource
Development

• Study design assistance and execution
• Permit and promote data sharing through
  interoperability
• Resource development and integration at multiple
  sites
• Data curation and integration

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CBCB Infrastructure HW/SW

• 190 Computer Systems, 224 processors,
• 115 GigaBytes RAM, 2.7TeraBytes of Disk
• 5 dedicated clusters
• 32 CPUs, 64 GB RAM, 1.0 Gigabit copper Ethernet
  N/W, Linux
• 32 CPUs, 20 GB RAM, 1.0 Gigabit fiber Ethernet
  N/W, Linux
• 18 CPUs, 9 GB RAM, 2.4 Gbit Multistage N/W, Linux
• 17 CPUs, 8GB RAM, ATM N/W, SUNOS
• 8 CPUs, 1 GB RAM, 100 Mbit and ATM N/Ws, Linux
• 9 compute, database, and file servers
• 40 Development systems
• 2000 Sq.ft. lab space (100 Mbit and Gbit
  Ethernet,
• and 802.11a/b wireless system).
• Extensive installed base of Software for genome,
  expression, and linkage study, and other analyses.

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CBCB Faculty Affiliates

• 5 Colleges
• More than 25 Departments/Programs

• Dr. William Ballard (Biological Sciences)
• Dr. Terry A. Braun (Biomedical Engineering)
• Dr. Adrian H. Elcock (Biochemistry)
• Dr. Caroline S. Harwood (Microbiology)
• Dr. Jian Huang, (Statistics and Biostatistics)
• Dr. Kenneth P. Murphy (Biochemistry)
• Dr. Todd E. Scheetz (Ophthalmology)
• Dr. Deborah L Segaloff (Biophysics)
• Dr. Alberto M. Segre (CS, Applied Math, CSG)
• Dr. Val C. Sheffield (Pediatrics, Genetics)
• Dr. Edwin M. Stone (Ophthalmology, Genetics)
• Dr. Debashish Bhattacharya (Biology, Genetics)
• Dr. Kevin Campbell (Physiology and Biophysics)
• Dr. James F. Cremer (Computer Science)
• Dr. Robin Davisson (Anatomy and Cell Biology)
• Dr. Beverly Davidson (Internal Medicine,
  Genetics)
• Dr. Connie Delaney (Nursing, Health Informatics)
• Dr. Robert Deschenes (Biochemistry, Genetics)
• Dr. John Donelson (Biochemistry)

• Dr. David Eichmann (Library/Information Science)
• Dr. Jan Fassler, (Bilogical Sciences, Genetics)
• Dr. G. F. Gebhart (Pharmacology)
• Dr. E. Peter Greenberg (Microbiology)
• Dr. Ramon Lawrence (Computer Science)
• Dr. Matthew Howard (Neurosurgery)
• Dr. Khalid Kader (Biomedical Engineering)
• Dr. Robert J. Linhardt (Pharmacy, Chemical
  Engineering)
• Dr. Michael Mackey (Biomedical Engineering)
• Dr. Paul McCray, (Pulmonary Pediatrics)
• Dr. William Nauseef (Internal Medicine)
• Dr. John P. Robinson (ECE)
• Dr. Curtis Sigmund (Physiology and Biophysics)
• Dr. M. Bento Soares (Physiology, Biochemistry,
  Genetics)
• Dr. Padmini Srinivasan (Library/Information
  Science)
• Dr. Mark Stinski (Microbiology)
• Dr. John B. Stokes (Internal Medicine)
• Dr. Jerrold Weiss (Internal Medicine and
  Microbiology)
• Dr. Michael J. Welsh (Internal Medicine)

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CBCB/CLCG People

• Post-Docs/Sr. Computational Scientists
• Dr. Todd E. Scheetz, Dr. Tom Bair, Dr. Vladimir
  Leontiev
• Staff
• Erin Brothers, Hakeem Abdulkawy, Jason Grundstad,
  Gregg Webster, Dr. Bartley Brown, Dylan Tack,
  Jason Laffin, Rhett Sutphin
• Students
• Annie Chiang, Nishank Trivedi, Jesse Walters,
  Brian OLeary, LaVonne Mangin, Paul Song, Steve
  Davis, Jared Bischof, Brian Mokrzycki, Barry
  Gackle, Rani Kalari, Kevin Jenner, Chris Moressi,
  Mike Smith