Download PGRN-RIKEN Proposal Submission We are encouraging

PGRN-RIKEN Proposal Submission
We are encouraging applications from a broad group of investigators who are members of the
PGRN or have recently applied for membership (see http://www.pgrn.org/join.html). Applicants must
have samples from pharmacogenomics studies of well-phenotyped patients. The review process will
involve reviewers who have approved PGRN-RIKEN projects (http://www.pgrn.org/pgrn-riken.html).
Applicants with projects that have been selected for a PGRN-RIKEN collaborative study must agree to
(a) review proposals if requested; and (b) attend PGRN-RIKEN meetings (at your own expense). The
new PGRN-RIKEN collaboration is evolving and continues to expand. We encourage both types of
proposals for sequencing and genomewide association studies. In particular, applications from
investigators who are studying drugs that have not been previously studied using genomewide
approaches, or new phenotypes of drug response that have not been studied. Such phenotypes may
include hard endpoints, e.g. rather than statin-associated change in LDL-cholesterol, a new
phenotype might be time to a cardiovascular event on statins.
Timeline for PGRN-RIKEN Proposals, Round 15
September 19th, 2016 (Monday) by 9 am Pacific Time: Proposals due from investigators.
September 21st, 2016 (Wednesday): Proposals assigned to reviewers (members of the past PGRNRIKEN collaboration).
October 13th, 2016 (Thursday): Proposals reviewed on a call by the members of the past PGRNRIKEN collaboration.
October 24th, 2016 (Monday): Final revised proposals due from investigators.
October 28th, 2016 (Friday): Approved proposals sent to RIKEN.
November 28th, 2016 (Monday): Proposals accepted for presentation by RIKEN.
January 18th and 19th, 2017 (Wednesday, Thursday): Presentations and Meeting in Yokohama,
Japan.
Instructions and criteria for PGRN-RIKEN Proposals, Round 15
We will accept two types of proposals: one is the usual proposal focused on genome-wide association
studies (see Section 1), and the second is a new proposal to perform deep sequencing (see Section
2). Two types of sequencing proposals will be accepted; one for sequencing around previously
identified gene regions within the past PGRN-RIKEN projects (Round 1 to Round 14) (see Section 2),
and the other for sequencing of one or more specific pharmacogenes, which can be from current or
new projects. The list of specific pharmacogenes is appended.
Send any questions to Dr. Sook Wah Yee at [email protected]
SECTION 1: Submission for Genome-wide Association Study
1. Proposal Format (GWAS):
Apply according to the following format. If not compliant with the following, the proposal will be
returned without reviewed.
1. One page cover with study title and all investigators involved (indicate PI and Co-PI), with their
affiliations and funders listed (also indicate which PGRN groups or the name of the funded
pharmacogenomics research)
2. Three page length overall for the submission with these elements:
a. Background including other studies in the field
b. Importance of the problem to pharmacogenomics
c. Population to be studied, and description of any approvals needed from collaborators
d. Phenotypes that will be analyzed (description of primary endpoint/s, other information
that may be available)
e. Genotyping requested, with justification for approach
f. Statistical analysis plan, including power calculations
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g. Data deposits plan, and statement of consent status (for Genome-wide Association
Study).
h. Data analysis and replication plans, within appropriate time line
i. Functional follow up plan to reveal the mechanism of the SNP
j. Statement of agreement to follow Standard Operating Procedures (SOPs). Contact
[email protected] to request a copy of the SOP.
3. Proposal may be resubmitted in a subsequent call if they are responsive to the concerns of the
reviewers. Resubmission applications must include a short paragraph at the beginning of the
proposal indicating how the proposal has been changed to reflect the concerns expressed by
the reviewers.
4. Submit as a single pdf file to [email protected].
5. PIease include a statement that a PI on the project will be present for the meeting in
Yokohama, Japan.
2. Criteria for evaluation of genome-wide association study (by past PGRN-RIKEN members)
1. What is the scientific merit of the proposed study? Scientific merit will include the significance
and innovation of the proposal.
2. Is the sample size adequate and is the statistical plan appropriate? (evaluation by statisticians
selected by the PGRN-RIKEN Leadership)
3. Do proposals meet the following qualifications?
a. Are the DNA samples ready-to-ship, and will the phenotype data for the studies be ready
within 6 months from the study’s approval?
b. If the situation is anything other than samples ready-to-ship, is there reason to proceed now
rather than wait?
c. Did the investigators agree to SOPs?
d. Does the proposal conform to the required format guidelines? (see above)
4. Plan to attend and present at the meeting.
SECTION 2: Submission for Deep Sequencing Study That May Include the Top
Pharmacogenes (see Table 1) or Specific Loci With Appropriate Rationale
1. Proposal Format (Deep Sequencing):
Apply according to the following format. If not compliant with the following, the proposal will be
returned without reviewed
1. One page cover with study title and all investigators involved (indicate PI and Co-PI), with their
affiliations and funders listed (also indicate which PGRN groups or the name of the funded
pharmacogenomics research).
2. Three page length overall for the submission with these elements:
a. Background including other studies in the field
b. Importance of the problem to pharmacogenomics
c. Summary of previous GWAS results if applicable
d. Rationale for proposed sequencing
e. Sequencing requested - specify loci to be sequenced and samples. Provide brief
rationale for each loci and for the samples.
f. Specific gene information – gene name(s), length of coding region, information for
pseudogene and family genes, priority of each gene (Number of genes is assumed to
be less than 30. Final gene list to be sequenced is determined after the discussion with
RIKEN). Investigator can also propose to sequence the top pharmacogenes and
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simply select any genes from the gene list irrespective of gene group/category (see
Table 1).
g. Study Design Plan, including power calculations
h. Data analysis plan, within appropriate time line
3. Proposal may be resubmitted in a subsequent call if they are responsive to the concerns of the
reviewers. Resubmission applications must include a short paragraph at the beginning of the
proposal indicating how the proposal has been changed to reflect the concerns expressed by
the reviewers.
4. Submit as a single pdf file to [email protected].
5. PIease include a statement that a PI on the project will be present for meeting in Yokohama,
Japan.
2. Criteria for evaluation of deep sequencing study (by past PGRN-RIKEN members)
1. Are the samples requested for deep sequencing from PGRN-RIKEN projects (Round 1 to 14)?
If not, are they new projects for specific pharmacogenes?
2. What is the scientific merit of the proposed study? Scientific merit will include the significance
and innovation of the proposal.
3. Is the sample size adequate and is the statistical plan appropriate? (evaluation by statisticians
selected by the PGRN-RIKEN Leadership)
4. Is the deep sequencing project well-rationalized?
5. Do proposals meet the following qualifications?
a. Are the DNA samples at RIKEN and enough for deep sequencing? (> 1 μg)
b. Are the phenotype data for the studies sufficient and ready for the association analysis?
c. Does the proposal conform to the required format guidelines? (see above)
6. Plan to attend and present at the meeting in Japan.
POST-SELECTION RESPONSIBILITIES FOR PRINCIPAL INVESTIGATOR:
1. Plan to attend the PGRN-RIKEN Calls (2nd Thursday of each month), or send a very informed
representative as needed. Plan to respond to all requests for information (for PGRN oversight,
communication and coordination, and sharing of “best practices” network-wide).
2. Plan to work directly with your assigned RIKEN collaborator for coordination of the particulars of
your study (for sample preparation and plating, shipping dates, review of data quality and analysis
of results, and publications). Within 6 months of the study’s approval, samples should be sent to
RIKEN, and all phenotypic information for the data analysis should be ready.
3. Plan to attend the PGRN-RIKEN meetings, typically once or twice per year at alternating locations
between the US and Japan.
4. These are collaborations, and communication should be bi-directional about data analysis, results,
and planned replication studies (remember that the PGRN-RIKEN is facilitating this collaboration,
and please credit).
5. Immediately after selection, and thereafter as needed:
a. Submit monthly updates (e.g. shipping and data receipt dates, IRB clearances, status of
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results, abstracts & papers, etc.) during monthly calls or by e-mail to [email protected].
b. Be a reviewer if requested by the PGRN-RIKEN Leadership.
6. Immediately after publication of the genomewide association study, the summary statistics of the
data will be deposited to PGRN-RIKEN website as a pharmacogenomics resource to other
studies. Any researcher who uses your data should acknowledge your publication.
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Table 1. List of 100 Pharmacogenes.
Group
Group 1
Group 2
Category Core Pharmacogenes Genes expressed in liver
Gene list
Updated July 2016
CYP1A2
CYP2A6
CYP2B6
CYP2C19
CYP2C8
CYP2C9
CYP2D6
CYP2E1
CYP3A4
CYP3A5
CYP4A11
NAT2
UGT1A1
CES1
ABCB1
ABCC2
ABCG2
SLCO1B1
SLCO1B3
VKORC1
CYP2C18
CYP2J2
CYP3A7
CYP3A43
CYP4F2
CYP4F3
CYP4F12
FMO3
FMO5
UGT1A3
UGT1A4
UGT1A6
UGT1A9
UGT2B7
UGT2B10
UGT2B15
UGT2B28
SULT1A1
SULT1A2
CES2
GSTM1
ABCB11
ABCC3
SLC10A1
SLC22A1
SLC22A9
SLC29A3
SLC47A1
SLCO2B1
POR
Group 3
Genes expressed in other
tissues
CYP1A1
CYP1B1
CYP4B1
FMO1
FMO2
FMO4
GSTA1
NAT1
SLC10A2
SLC15A1
SLC22A2
SLC22A5
SLC22A6
SLC22A8
SLC22A11
SLC28A1
UGT1A5
UGT1A7
UGT1A8
UGT1A10
Group 4
Genes expressed in multiple
tissues
ABCC1
ABCC4
CYP11A1
CYP17A1
CYP19A1
CYP2A13
CYP2S1
CYP2W1
CYP26A1
CYP4F8
CYP4Z1
GSTT1
GSTP1
SLC15A2
SLC16A7
SLC19A1
SLC22A3
SLC22A4
SLC22A12
SLC28A2
SLC28A3
SLC29A1
SLC29A2
SLC31A1
SLC46A1
SLC47A2
SLCO1A2
SULT1E1
SULT2B1
TPMT
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