Area 1 Conference Call Minutes
December 11, 2012
Present: Chris Amos, Tao Le, Heike Bickeboller, Saskia Freytag, Maria Tere Landi,
James McKay, Maria Timofeeva, Younghun Han, Darren Brenner, Judi Forman, Lamar
Moss
1. Update on transition of grant
Amos:
- The funding is at Dartmouth and we are now issuing the subcontracts. The
goal is to disperse the monies by the beginning of 2013. All of the MOUs are
in place except those between DKFZ, UMG and MDACC. MDACC also needs
to do an MTA. Tao Le is working on an MOU. It is at legal right now. The
MOU with NCI has been finalized here and has gone back to complete the
component dealing with human subjects.
-
Judi will follow-up with Heike about MOU. Munich also has a problem.
Somebody insisting that they do the contract together so that was holding up
the process.
2. Updates on meta-analysis using HapMap 2 and 1000 genomes
Amos:
- We have finished that except for NCI data (not included for HapMap 2, held
up due to no MOU yet). Space on server at NCI has been increased so DTI,
FOCI, CORRECT, and TRICL are uploaded (need ELIPSE). Each group has
a reporter so whenever data analyses are conducted they will be reviewed by
Rayjean (who is the reporter for TRICL). The analyses that we have done we
can use, but if data is across U19 group then it has to be approved by the
Working Group and the Steering Committee for all the U19s. We can look at
our own data for TRICL.
-
Rayjean is designated as reporter since she is involved in the uploading of
the data. Summary p-value, odds ratio over all the studies, and R2 values for
each independent study is uploaded now (meta-analytical results).
-
Younghun conducted meta-analyses across the groups. We need the sample
size for each study. We also want to do 1000 genome meta-analyses. We will
do TRICL analysis and then upload summary data for all the groups. Yufei is
doing imputation using additional data that he has. We are also going to do
1000 genome meta-analysis. The purpose of the current meta-analysis is to
do HapMap 2. All other GAME-ON members are doing 1000 genome so we
are planning to do it too. The plan is for everyone to upload summary data to
Dartmouth. We don’t have the same constraints on ownership of data at
Dartmouth as we did at MDACC. Access will not be cut off due to lack of
personnel.
-
Heike and Albert have asked to do imputation at MD Anderson and Chris
needs to follow-up. DeCODE is doing imputation and should be close to being
done. We should proceed with this analysis to identify SNPs that will be
placed on the Oncochip platform? Need to make sure German group is
getting imputed. An order for replication genotyping has been placed with
Affymetrix. We are hoping to have arrays delivered before Christmas. We
need shipping of samples to happen from the different sites.
-
Some samples are coming from Toronto.
-
Hongbing cannot send samples outside of China so we are seeking a
genotyping center that he can use there. It will take a few months. Avoiding
downtime while we are waiting for samples is important.
Tere:
- (Tere requested clarification on access to data though TRICL) Since we have
the MOU we give the data to Yufei to analyze 1000 genome data. You have
to reduce it to the HapMap 2.
-
If we send data to Illumina directly we don’t need a contract. Would it be the
same for Toronto since it is a service lab?
Yufei:
- We are still waiting on data from Maria.
-
Yufei has access to Dartmouth. It took one week to upload data (?). Dakai
Zhu sent out directions to access it last week.
-
I need summary data to upload to storage from each group. MD Anderson
and Maria still need to submit data. Tere is going to upload summary results
to Dartmouth as soon as MOU is signed.
Rayjean:
- After DNA is dried and shipped there is some degradation. Did not pass
quality control. We would not recommend that anyone send DNA in glycolized
form.
-
We have started to receive the sample manifest.
-
MTA with IARC – not sure of MTA applies if you are sending to service lab?
(James indicated that this is correct).
3. Fine mapping update
Amos:
- Yufei is pursuing this. He said he has identified some interesting findings but
needs additional data to confirm findings.
4. Development of GAME-ON chip
Amos:
- We submitted two applications to TRICL.
-
GAME-ON application is under review. There is ongoing review of how to
allocate the number of SNPs and uploading data.
-
We need to identify which institutions will be contributing, could do analyses,
and could upload data to dbGAP. We would then be able to do 20,000 cases
and 20,000 controls. We need to see which centers can contribute based on
their protocols.
-
There is going to be a process of SNP selection. Opportunity for Yufei to have
SNPs replicated. The GAME-ON chip has 210,00 samples to be analyzed at
CIDR. We would need to start genotyping in June 2013. SNP selection would
be end of March 2013. We could wait until after the meeting in January. We
need to present limited epidemiological data.
5. Pathway analyses
Saskia:
- We are working to identify pathways associated with lung cancer. We have a
finished program that everyone can use. Toronto has already implemented
our method. Both top 10 results had circadian rhythms. This may be
implicated in cancers. Chris is planning to analyze data with MD Anderson.
We have changed our model to include network structure. We are still in the
process to find the best way to present gene-gene interactions. We are
hoping to find best representation and then give programs to all centers to be
able to compare.
-
Heike: Hoping to join IARC data.
-
Amos: Rayjean has a lot of data but is overwhelmed.
-
Tere: (Amos: Tere could start on pathways. R-script is ready now). I will send
Heike an e-mail to follow-up about MOUs.
6. Histology analyses
Rayjean:
- Now under revision in human genetics. Need to work on regional imputation.
-
We have four candidates. Looking at chromosome 17 and 18. Some of
variants show up in 550 but not 317. Working on Japan study and Mayo
study.
-
Chinese and Japanese studies will be analyzed separately. We will study
them for generalizability. Results could also be studied in Nat Rothman’s
study. Between Japanese and Chinese regions, we have enough information.
-
Tere: Will this affect meta-analysis results? (Amos: Hard to predict because
Yufei does not have that much done yet).
-
Amos: Gerry Coatzee is trying to predict functional SNPs (FUNCI SNPs).
7. Further development of statistical methods for meta-analysis
Amos:
- Albert is not on the call.
8. Updates from sequencing
Amos:
- There is a target region on 6q that has been sequenced by GELCC.
-
The sequencing is done on exome from GELCC (not reported yet).
-
Wash U – Whole genome sequencing for GELCC (no update), but samples
have been shipped.
-
GLCC GWAS – It will be a while before any update.
-
We started to look at TCGA. The idea is to integrate summary results from
GWAS with expression studies. TCGA is not very good, has expression but
not normal matching data. We want to integrate meta-analyses with
expression data from genome. We want to see if joint analysis brings forward
anything. We should have a separate working group to work on that. We
should look into using the kernel machine learning tool. First, learn to use Rscript. Would like to develop grant to encompass all of GAME-ON but that
could be challenging. We need to show that we are working with TCGA data,
but it is not all that useful for initial discovery. Dr. Amos suggests developing
two grants for the February-March deadline. One grant will focus on using the
Kernel Machine Test method that Saskia and Heike have developed for genelevel and pathway-level analysis. The other grant would focus on further
studies of the CDKN2 region findings. Dr. Amos worked with Ivan Gorlov at
MD Anderson to submit a grant that uses GEO data to develop functional
annotation of expression data and integrate that with GWAS findings, then
confirm using samples from Dartmouth.
-
Heike: Received agenda for January meeting. Not sure if I need an invitation.
I have booked my flight to attend. I need to know if there is anything to
prepare for a presentation.
9. Action items
- Disperse the subcontract monies by the beginning of 2013.
- Complete MOU and MTA with MD Anderson.
- Judi will follow-up with Heike about MOU.
- Tere will send Heike and e-mail about MOUs (to conduct pathway analyses).
- Determine MOU status with Munich.
- Collect sample size for each study for meta-analysis (finished).
- 1000 genome for GAME-ON.
- Upload summary data to Dartmouth.
- Contact German group about doing imputation at MD Anderson.
- Collect data from Maria for fine mapping.
- Send Yufei summary data to upload to storage.
- Follow-up on meta-analysis using HapMap 2 and 1000 genomes (e.g. using
Illumina/establishing contracts with service labs; determine method of
receiving samples from Toronto; status of incomplete MOUs and sending
data to Yufei).
- Replication studies: Collect separate MTAs for samples. Check with IARC
administration regarding data guidelines.
10. Next meeting
-Tuesday, January 8, 2013 at 10:00 A.M. EDT