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CTRF Leadership Meeting
June 3, 2002
Institutional Partners
V C U G M U I N O V A
5/06/02
Minutes
Corrections
Approval
Develop Infrastructure and Intellectual
Property that Enhances the Competitiveness of the Partners for Clinical and Extramural Funds
Principle Objective
Evaluate gene expression (and genetic changes) in human brain, ovarian, breast and hematopoetic cancers
Link gene expression (and genetic changes) to clinical findings and clinical laboratory findings (including histopathological diagnoses) in a common database
Evaluate linked data using bioinformatics
Research Objective
ChandhokeGrant
ChristensenFryxell
Jamison
Torr (Central Admin)GinderGarrettBuck
Guiseppe-ElieAbraham
Cooper
Year 1 Year 1 Year 1
$325,000 $582,000 $93,000
Total (3 yrs) Total (3 yrs) Total (3 yrs)
$975,000 $1,734,603 $290,397
Year 2 Year 2 Year 2
$325,000 $578,191 $96,809
Funding From CTRF
DRAFTFiscal Year 2002
Budget Summary Report
CTRF
Account
# PI
June 30
Expenses
Estimated
July 1
Balance
Matching
Funds to Date
535282 Main Account 33,195.44$ 43,839.00$
535283 Garrett 9,312.75$ 169,597.00$
535284 Buck
535286 Guiseppe-Eli 107,728.73$ 148,679.03$
535285 Ginder 93,382.76$ 13.24$
535288 GMU
535286 Inova
Reminder - Cost Share Form (VCU)
Cost share expenditures not paid from cost share linked ledger 4 account must be documented using ‘In Kind/3rd Party Cost Share form’ obtained from Margie Booker’s office. (http://www.vcu.edu/finance/In-kind%20Cost%20Sharing%Certification.pdf)
Cost Share Expenses
FY 02 Rollover
• Rollover process will utilize appropriation adjustments required to be available on July 1, 2002 (Federal fund carry-forward process)
• Automated Transaction System (FATS) request must be submitted between June 12 and 14th
– Summary of budget status (Carry-Forward Form)
– Justification (Transaction brief)• Justification and Carry-Forward Form to be
submitted to Dr. Garrett by June 7, 2002
Request to Carry Forward Form
Justification (Transaction Brief)
Reason for year-end balance:The project began late. Funds were not identified
until 3 months after the programmatic start date. In addition there was a delay in recruitment of key personnel (ex the director of the tissue acquisition service at VCU did not arrive on site until Dec 2002).
Need for carry-forward of these funds:Use of the unexpended funds are essential to
continue the project and carry out the programmatic aims of the grant. There are no alternative funds to achieve the specific aims of the grant. In addition, the institutional partners have already made significant matching obligations to this project.
How the funds will be used:Funds will be used consistent with the grant
proposal
FY 03 Allocation
• [Submit record of expenditures and matching funds (FY02 Closeout)]
• Will need to submit progress indicating milestones achieved in FY02 (in prep - C. Garrett)
Website Update
CTRF “News and Updates” page will be added to site
Focus Group roles and responsibility still needed from Focus Group Leaders
URL for site is: www.ctrf-cagenomics.vcu.edu
SPIN Research Jo Ann Breaux receiving daily notices of
grant opportunities Compiling weekly document of relevant
findings Will be distributed over the CTRF
LISTSERV
SMART documents currently on the CTRF website
• Training is available: http://www.InfoEd.org/default.stm
Tissue Bank Clinical and Pathology Laboratory Data Database Design Data Analysis Quality Assurance in Microarray Analysis (Chip Fabrication - proposed)
Focus Group
Focus Group Leaders
G MU
G e rald in e G ran t ( G M U )S u ha il N as im ( V C U )B a rr ie C o o k ( I n o va)
Tissue Bank
L yn ne P en b e rth y (V C U )S u ha il N as im ( V C U )
J a m e s C o op e r ( I n o va)J a m e s B u rge s s ( I no va)
B a rr ie C o o k ( I n o va)
C linP ath
C u rtis J am is on ( G M U )L yn ne P en b e rth y (V C U )
G re g M ille r (V C U )M ike S he ride n ( I no va)
D B D esign
V ika s C h an d h oke ( G M U )G re g B u ck ( V C U )
D ataA nalysis
A la n C h ris ten s en ( G M U )A n d re a F e rre ira - G o n z ale z (V C U )
Q A / LQ C
VCU I nova
Focus Group Leaders
• IRB approval at INOVA
• Tissue Acquisition person to be hired and managed by Marianne Smith
– Inova to work out process for obtaining necessary informed consent
• Tissue Bank person to go to OR area with pathologist responding to request for frozen section and take tissue at that time
• Ideal procedure is unclear at this time for tissue acquisition unclear:
– Cut and freeze a piece of tissue at the OR (most rapid)
– Perform a frozen section on a block and then drop the latter into liquid nitrogen (delay 5-10min)
• Protocol handling for Bone Marrow Aspirates not yet specified
• Tissue is not to leave Inova until surg path written report is completed
INOVA -CTRF - Tissue Bank
VCU - Tissue Bank
• TAS approved by IRB 4/15/02
• Tissue Bank Staff Activities (Cynthia Losco)
– Procedures Established in Main OR and Ambulatory Surgery
– Cynthia to be notified 30 minutes before specimen to be ready on cases identified for CTRF eligibility
– In-service given to OR staff to address new procedure
– Bone Marrow Biopsy patients are being consented directly after procedure
Specimens Acquired
Organ Number ofSpecimens
Breast 8
Bone Marrow 14
Ovary 3
Brain 0
Manual Form for Tissue Acquisition
Histopathologic Parameters
Tissue Acquisition Database
• Access Database
• To Contain Inova and VCU Cases
• Demo Today after Leadership Meeting
Tissue Utilization(1)
Non-anonymized tissue samples are a form of patient medical record
The health system where the medical record is created is responsible for access and integrity.
Personal identifying information should be maintained behind a health systems firewall.
Tissue Utilization(2)
Each health system which creates non-anonymized human tissue sample banks will:ο identify a guardian who is
responsible for maintenance of the integrity of the collection and monitoring utilization.
ο establish a tissue utilization committee to formulate criteria for use of samples.
Institutional Tissue Utilization Committee
Formulate criteria for who is eligible to obtain human residual samples at the institution.ο Faculty status, IRB approval, ?
scientific validityο ?minimum QA requirementsο ?minimum data access
requirements Review requests for human tissue
utilization. Formulate criteria for the degree of
clinical information which can be provided with the samples.
Assess resources required to fill request and whether PI is prepared to provide them.
Tissue Utilization(3)
For purposes of regulating utilization of all samples collected by CTRF tissue collection personnel for the CTRF Ca Genomics Project, it is assumed that:ο the VCU and Inova tissue utilization
committees agree to follow the criteria and decisions regarding tissue utilization as determined by the CTRF Ca Genomics Project Tissue Utilization Group.
CTRF Ca Genomics Project Tissue Utilization Group
• Project PIs• Tissue Guardians• ?Other Project Leadership• Issues
– QA Program– Pre-Analytical Tissue Handling
• Storage Conditions (Freezer Monitoring, etc)
– Manner in which tissue is supplied– Storage and availability of data
Tissue Utilization Summary
VCU TissueCommittee
Inova TissueCommittee
CTRF TissueUtilization Group
Analyze Samples
Database Design/Clinical Info
Clinical Data ElementsDefine minimal set of common clinical
data elements; Initial choice to be the elements required to be sent to state cancer registry
Data elements should include MIAME (Minimum Information about a Microarray Experiment) for holding Expression Array Data
GeneX Database – Initial choice for storing project data
GeneX Database (Update) GMUVCU
“Terabyte” Database – (Update)VCU
LabBook (Update - Buck) VCU
Database Design/Data Analysis
Schema (VCU Preliminary) 16 Chips
Test for Variation Chip-Chip Labeling Buffers Modules (4)
Update – VCU/GMU
QA/QC
Normalization and ControlsMethod DescriptionArabidopsis The MWG 10K human oligo set comes with arabidopsis controls for
hybridization verification. Positive controls for hybridization.
Housekeeping Genes spotted to determine the basal level of expression
Pin Normalization To normalize the variation in deposition of oligos by the spotting pins
Spiking Known amounts of labeled oligo, which are specific for a subset of arrayed probes, are included in the hybridization fluid.
3’/5’ Ratio The 3’ and 5’ end of certain defined genes will be arrayed. The ratio of the intensities will be taken as an indication of the mRNA degradation
Global The global intensity average will be used to normalize the intensity of the individual spots.
Dynamic Range A subset of oligos are spotted in a concentration gradient, and the hybridization buffer is spiked with the labeled complement. The resulting intensity gradient yields information on hybridization uniformity, sensitivity, and dynamic range. The dynamic range yields info on validity of signal as a function of the signal to noise ratio.
Yellow slide An mRNA sample is labeled with both Cy3 and Cy5 in equal ratios. After hybridization the slide is used to balance the laser power.
Two slides/ Flip Each microarray experiment will be done on 4 slides. mRNA (Sample and Control) is each labeled with two dyes. 2 slides are hybridized with RED Sample and GREEN Control, 2 slides are hybridized with GREEN Sample and RED Control.
Suggestions for Array Design Among CTRF Members
• Spiking: Include the same spiking genes used on the Affy chip, on the C3B and GMU chips
• 3’/5’ controls: Include the same genes used on the Affy chip. Can they be added to the GMU chip?
•Dynamic Range: This can be implemented on the C3B and GMU chips.
• Pin Normalization: This is a statistical routine in the R software package, this can be implemented on the C3B and GMU chip.
• 5 Slide Experimental Design
5 Slide Experimental Design
1 2 3
1-Yellow1-Yellow2-Std2-Std3-Flip3-Flip
C C
1
C S S C
32
2/1=Actual Fold change Std = 2’3/1=Actual Fold change Flip = 3’2’/3’=1
Microarray Format for the MWG 10K Human Oligo Set
66.95 mm
16.55 mm
KEY
Houskeeping
Spiking & 3’/5’
Dynamic Range
Empty
Replicate Array 1 Replicate Array 2
Establish Standing Weekly or Biweekly Meeting Dates and Times
Complete the Milestone Updates
Document Discussions and Progress Using Listservs
REMINDER
CG-TISBK: Tissue Bank CG-CLNDT: Clinical and Pathology Data CG-DBDSN: Database Design CG-ANLDT: Analyze Data (Data Analysis) CG-QAQC: QAQC CG-LDRPI: Focus Group Leaders and PIs CG-MEMBS: All Members
Communication Amongst Members and Focus Groups
Address messages to: [email protected]
Unsubscribe to the listserv by submitting a message with the words SIGNOFF listname to: [email protected]
Subscribe to the listserv by asking the PI with whom you work to submit your name and E-mail address to the Program Director (C.Garrett)
USE the listserv(s) to inform members of your activity or to seek advice from the members.
LISTSERVS
Old Business
New BusinessoC3B Presentations at BECON2002 Symposium
Intellectual property reporting - licenses, patents, etc
Publications
New applications
CTRF Administrative office
will search for new funding opportunities (SPIN)
will collect CVs, other support, facilities, interest documents
goal - 4 - 8 million in d.c. from CTRF CG Project
5/21/02 - 1 million (1yr) submission to VTSF (Penberthy-PI)
Any other discoveries
Federal money leveraged
Private research money leveraged
Advancement of technology and economic development in VA
CTRF - Specific Reportables - - Reminder - -
Monday
July, 1 2002
9:30 am