Whole-Genome Analysis for Autism Risk Variants Request for Applications
Grants awarded through this RFA are intended to advance our understanding of the genetic basis of autism, and in particular, to begin to assess genetic variants conferring risk in non-coding regions and in coding regions of the genome that may be less accessible to whole-exome sequencing. Investigators who are interested in developing innovative and efficient ways to analyze whole-genome sequencing data from 500 Simons Simplex Collection (SSC) families are encouraged to apply. The maximum budget is $250,000, including indirect costs, for eighteen months, non-renewable.
$250,000
- Email intent to submit proposal
- Application deadline
- Notification of award
- Funding expected to begin
-
SFARI Grant Programs
sciencerfa@simonsfoundation.org
SFARI mission
The Simons Foundation Autism Research Initiative (SFARI) seeks to improve the understanding, diagnosis and treatment of autism spectrum disorders by funding innovative research of the highest quality and relevance.
Objective and rationale
Grants awarded through this request for applications (RFA) are intended to advance our understanding of the genetic basis of autism, and in particular, to begin to assess genetic variants conferring risk in non-coding regions and in coding regions of the genome that may be less accessible to whole-exome sequencing (WES).
The Simons Simplex Collection (SSC) is a rigorously characterized collection optimized to support the discovery of genetic events that increase risk of developing autism. The collection consists of approximately 2,600 simplex families, all of which have one child with autism, unaffected parents, and in over 80 percent of families at least one unaffected sibling. Analyses based on WES data from the SSC have already identified at least 30 risk genes for autism and have nominated several hundred other genes as strong candidates1,2.
Whole-genome sequencing (WGS) of the SSC is expected to increase the detection of rare variants of clinical importance. In addition to identifying variants in non-coding regions of the genome, WGS analyses are anticipated to identify novel copy number variants (CNVs) and single nucleotide variants (SNVs) in protein-coding regions that have not previously been detected with WES. Preliminary WGS analyses of a separate group of 40 families (160 genomes) from the SSC compared WGS results with WES data from the same 40 families and support the value of WGS in identifying additional variants of potential clinical significance for autism.
To this end, SFARI has partnered with the New York Genome Center (NYGC) to sequence whole-genomes from the whole blood DNA of 500 SSC quartet families (2,000 genomes at 30X sequence coverage).
SFARI plans to make the alignment and variant call data available to all eligible researchers (i.e., not contingent on funding through this RFA) without delay following standard quality control and data processing steps by the NYGC. The first batch of data will likely be available starting in October 2015, and it is anticipated that 90 percent of the WGS data will be available by January 2016. There will be a publication embargo on whole-genome analyses that prevents submission of manuscripts for publication until SFARI has announced that data generation for the full cohort is finished and has passed quality controls and that a first level due diligence on confirmation of calls is complete.
SFARI will work with successful applicants to make the WGS data (estimated to be about 400 TB) available to their academic or cloud-based computing resources. SFARI understands that validation of prioritized hits is a key part of this project and will coordinate some of this confirmation of de novo calls with awardees and the NYGC.
The current RFA seeks applications from investigators who plan to develop innovative and efficient ways to analyze WGS data from the 500 SSC families.
Proposals of particular relevance to this RFA include, but are not limited to:
- Analyses of de novo and inherited mutations in exomes to identify coding variants not originally identified by WES.
- Analyses of de novo and inherited CNVs that were not identified by WES.
- Identification of non-coding variants associated with autism risk, including the potential development of novel algorithms/tools to analyze intronic and regulatory regions of the genome.
- Comparison of the current dataset with sequencing data from other autism and other neurodevelopmental disorders cohorts (including comparisons with WES data from SSC).
- Analyses of mitochondrial DNA.
Recognizing that successful analyses of such large datasets are likely to require multidisciplinary approaches, we encourage collaborations between investigators with complementary expertise.
Investigators should also note that proposals submitted in response to the RFA are expected to include plans to analyze the entire 500 family sample (rather than a subset of individuals).
Eligibility and collaboration
All applicants and key collaborators must hold a Ph.D., M.D. or equivalent degree and have a faculty position or the equivalent at a college, university, medical school or other research facility. Applications may be submitted by domestic and foreign nonprofit organizations; public and private institutions, such as colleges, universities, hospitals, laboratories and units of state and local government; and eligible agencies of the federal government. Applications may also be submitted by for-profit companies, in which case the funds provided for the grant are to be used only for charitable purposes toward research related to autism spectrum disorders. There are no citizenship or national residence requirements.
If the proposal includes investigators at more than one site, all investigators should have demonstrated prior success in similar collaborations.
Funding period and budget
The grant period is eighteen months. The maximum budget is $250,000 including indirect costs. SFARI may fund a number of projects as a result of this RFA.
Application requirements
Applications should include the following:
- Narrative, not to exceed six pages (excluding references, figures, and figure legends). Proposals should include specific aims, background relevant to the application, significance of the proposed studies, preliminary results, experimental design, pitfalls and alternative strategies, and a timeline with milestones.
- Biosketches for Principal Investigator(s) and Key Collaborators.
- Current and pending support for Principal Investigator(s) and Key Collaborators.
- Budget. The maximum budget is $250,000, including indirect costs. Exceptions with good justification will be considered but are not encouraged. Proposals should include a realistic budget sufficiently detailed for evaluation of needed resources. SFARI will work closely with investigative teams with competitive applications to arrive at a suitable budget. Indirect costs are limited to 20 percent of the modified total direct costs (see SFARI policies).
Applicants should detail a strategy and estimate a budget for confirmation of prioritized hits. But note that SFARI will coordinate and fund directly some of the validation for SNPs in a centralized fashion at the NYGC.
Applicants should detail a strategy and estimate a budget for computing costs (either cloud or academic computing facility). SFARI will pay directly for cloud storage costs so these costs need not be included.
Applications with multiple Principal Investigators from different institutions that would like to be paid separately must include a signed budget template and budget justification for each Principal Investigator’s institution. Applications with subcontracts must include a budget and budget justification. The budget template and budget justification are available for download in the proposal attachments section of proposalCENTRAL’s full application.
- Research environment and resources. Investigators should demonstrate access to appropriate resources for high-capacity data analysis and computation.
- Data-sharing plan. The plan should include the sharing of all analyzed data in addition to sharing any new algorithms/data visualization tools that are a direct result of this award. SFARI will work closely with awarded investigative teams to ensure that the plan includes timely dissemination of data.
For more details, see the Instructions document, which is available for download in the “Proposal Attachments” section of proposalCENTRAL.
Application deadline
We request that investigators who intend to submit a proposal send an email by 28 July 2015 with the intended investigators’ names and affiliations and their intended proposal’s title to grants@simonsfoundation.org with the subject line: SFARI WGA RFA Notice of Intent.
The deadline for full proposal submission is 14 August 2015. No extensions will be given. If you have any difficulties, please contact grants@simonsfoundation.org.
Competitive applications will receive external peer review. SFARI will make final funding decisions; notification of award is anticipated by 15 October 2015, with funding expected to begin 1 November 2015.
Instructions for submission
Applications must be completed electronically and submitted using forms provided at proposalCENTRAL. Please log in as an applicant, scroll to “Simons Foundation” and click on the program.
Contacts
Scientific inquiries:
sciencerfa@simonsfoundation.org
646-654-0066
Administrative inquiries:
grants@simonsfoundation.org
646-654-0066
SSC collection inquiries:
collections@sfari.org
646-654-0066
proposalCENTRAL:
pcsupport@altum.com
800-875-2562
The Simons Foundation uses an electronic grants submission process. All interested grant applicants must submit their applications online through proposalCENTRAL.
$250,000
- Email intent to submit proposal
- Application deadline
- Notification of award
- Funding expected to begin
-
SFARI Grant Programs
sciencerfa@simonsfoundation.org
$250,000
- Email intent to submit proposal
- Application deadline
- Notification of award
- Funding expected to begin
-
SFARI Grant Programs
sciencerfa@simonsfoundation.org
-
Frequently Asked Questions
Where do I submit my application proposal?
Applications are online and must be submitted online through proposalCENTRAL. New users first need to create a user account on proposalCENTRAL (https://proposalcentral.altum.com/). For instructions on how to create a user account, please see question number 2 below. For all users, log in and select “Create New Proposal” or click on the “Grant Opportunities” tab. Filter the Grant Maker by “Simons Foundation” and click on “Apply Now” next to the “Whole-Genome Analysis for Autism Risk Variants Request for Applications” program. Once all sections are complete and the attachments are uploaded, the “Submit” button will be activated.
How do I create a proposalCENTRAL user account?Go to https://proposalcentral.altum.com/ and click “Create One Now” under “First Time Users.” Fill in the required fields, check the boxes to agree to proposalCENTRAL’s “Terms of Service and Acceptable Use Policy” and then click “Save.”
Is the Notice of Intent required to submit a full application? Is it the same as a Letter of Intent (LOI)?No, the Notice of Intent is not required for application submission but we request that investigators who intend to submit a proposal send an email by 28 July 2015 with the intended investigators’ names and affiliations and their intended proposal’s title to grants@simonsfoundation.org with the subject line: SFARI WGA RFA Notice of Intent.
The Notice of Intent is not the same as a formal Letter of Intent (LOI). Approval is not required for application submission.
Can someone else (assistant, staff member, etc.) submit my application for me?Yes, you can add users with administrator access to the proposalCENTRAL application so that someone other than the Principal Investigator (PI) can edit and submit the application. To add another user, go to section 3, “Enable Other Users to Access This Proposal,” and complete the required fields.
Can postdoctoral associates apply as Principal Investigators?No, postdoctoral associates may not apply as PIs. All applicants and key collaborators must hold a Ph.D., M.D. or equivalent degree and have a faculty position or the equivalent at a college, university, medical school or other research facility.
Can multiple Principal Investigators apply for a grant?Yes, if the proposal includes multiple PIs at more than one site, all investigators should have demonstrated prior success in similar collaborations.
For projects that have multiple PIs at different institutions, applications must be submitted by the PI designated as the contact PI and his/her institution. All applicants and key collaborators must hold a Ph.D., M.D. or equivalent degree and have a faculty position or the equivalent at a college, university, medical school or other research facility, and must submit a biosketch and a list of current and pending support.
Applications with multiple PIs from different institutions who will be paid directly by the contact PI’s institution are considered subcontracts.
Does the Simons Foundation require letters of support or collaboration?We do not require letters of support or letters of collaboration for Co-investigators. If a letter is prepared, it can be uploaded as “Appendix: In-press papers on related topics.”
Is there a minimum percent effort for Principal Investigators or Co-investigators?There is no minimum percent effort required for any personnel, but we expect personnel, in particular PIs and Co-investigators, to have efforts that reflect their roles in the project.
What is required for a subcontract? Where do I add the subcontract budget and upload subcontract budget details?"Applications with subcontracts must submit a subcontract budget for each subcontract awardee and grant year. The applicant PI must include the direct cost budget totals for all subcontracts in the “Consortium & Contractual Direct” section and indirect costs for all subcontracts in the “Subcontract Indirect Cost” section. The subcontract budget can be downloaded and uploaded in the “Proposal Attachments” section of the full application on proposalCENTRAL.
What is the funding period? When will funding begin?The initial funding period is for eighteen months and up to $250,000, including 20 percent of the modified total direct costs (see SFARI policies), beginning 1 November 2015.
Can foreign institutions apply for a grant?Yes. Please upload, if available, a copy of your U.S. Internal Revenue Service (IRS) 501(c)(3) determination or equivalency letter as part of the application. The Simons Foundation requires a determination letter from the IRS stating exemption under 501(c)(3) and furthermore, either a 509(a)(1), (2) or (3) classification. If an international institution is selected for funding and does not have the aforementioned documentation, the Simons Foundation will require the institution to complete an equivalency determination with NGOsoucre (see SFARI policies).
Can for-profit companies apply for a grant?Applications may be submitted by for-profit companies, in which case the funds provided for the grant are to be used only for charitable purposes toward research related to autism spectrum disorders.
Are references, figures and figure legends included in the narrative six-page limit? How should they be included?References, figures and figure legends are not included in the page limit for the full proposal. Please attach them at the end of the six-page narrative in the same PDF file. The Simons Foundation’s preference is for figures to follow the narrative rather than be embedded in the text.
What can I include as an appendix?‘In-press’ papers can be included as appendices, as well as any papers that you consider essential for the work of the review committee (not more than three). Any other material should be included, if possible, in the narrative.
If you have video attachments for your proposal, please upload as an appendix (all file types are accepted). All appendices should be uploaded in the “Proposal Attachments” section of the application.
What are the font, font size and margin requirements?11-point, legible font and .5 inch margins.
How can I find out more about available biospecimens and other data available from the Simons Simplex Collection (SSC)?You can access and request information about the SSC biospecimens and data on SFARI Base. Please see our resources website for more information (/resource/sfari-base/request-data-and-biospecimens). If you do not have a SFARI ID, you must create one. If you have problems with the log-in or have questions regarding the collections, please email collections@sfari.org.
Do the annual budget limits include the cost of purchasing SSC biospecimens?No, SSC biospecimen estimated costs are not included in the budget limit. Prices for SSC biospecimens can be found in the price list on our website.
How were the 500 families from the SSC chosen to be sequenced out of a possible ~2,600?All families with likely pathogenic mutations in probands and siblings, as identified by previous CNV and exome analyses, were excluded. The selection of the final 500 families from the remaining list was randomized. The list of the IDs of selected samples (together with summary information) is available here. Detailed phenotypic information for all individuals is available via SFARI Base (https://www.sfari.org/resource/sfari-base/).
Can manuscripts focusing on a small number of genes be submitted for publication during the embargo period, which prevents submission of whole-genome analyses for publication until all data are deposited and QC is complete?SFARI will consider these on a case-by-case basis, but yes, it is likely that researchers will have permission to submit these types of manuscripts for publication.
Do researchers need to send a copy of manuscripts to SFARI in parallel to submitting to a journal?Yes, researchers must send a copy of manuscripts to SFARI in parallel to submitting to journals.
Does the PI need to sign the signature page?No, only the signing official is required to sign the signature page.
How are applicants selected?Applicants will be selected based on qualifications and experience with the topic(s) relevant to the program. Competitive applications will receive external peer review. Notification of application status is expected by 15 October 2015.
Is validating my proposal the same as submitting it?No. “Validating” the proposal checks for errors and omissions and will alert you to missing requirements of your Letter of Intent or application. If the application is complete, you must then click “Submit.” You will receive an email within ten minutes, and should contact pcsupport@altum.com if you do not receive confirmation and do not see your application in the “Submitted” tab or with the status changed to “Submitted.”
I get an error message citing a missing section when I try to submit.The “Validate” button reviews your application for missing sections. The submission instructions list the required sections and attachments. You must complete the missing sections listed. If you are still receiving error messages after completing and saving the indicated sections, please contact pcsupport@altum.com.
Where is the “Submit” button?The “Submit” button is located in the last section of the application. You will be unable to submit if you have not provided all the required information. If the problem persists, please contact pcsupport@altum.com.
Can I make changes to the application once it has been submitted?You must contact Simons Foundation to un-submit your full application before you can edit attachments or HTML sections. Please email grants@simonsfoundation.org or call 646-654-0066 if you would like to un-submit your application prior to the 14 August 2015 deadline.
Is there a confirmation email when I submit?A confirmation email is sent upon submission of the application. Please contact pcsupport@altum.com if you submitted your application and have not received a confirmation email within ten minutes. Make sure that spam filters allow emails from pcsupport@altum.com.
Integrating large-scale whole-exome data with whole-genome data
- Awarded: 2015
- Award Type: Targeted: Whole-Genome Analysis for Autism Risk Variants
- Award #: 385027
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Joseph Buxbaum, Ph.D.
Icahn School of Medicine at Mount Sinai -
Xin He, Ph.D.
University of Chicago -
Michael Talkowski, Ph.D.
Massachusetts General Hospital
Combining whole-genome sequencing data from Utah high-risk pedigrees and Simons Simplex Collection families
- Awarded: 2015
- Award Type: Targeted: Whole-Genome Analysis for Autism Risk Variants
- Award #: 388196
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Gabor Marth, M.D., Ph.D., D.Sc.
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Hilary Coon, Ph.D.
University of Utah
Discovery of regulatory variants underlying pediatric neurological disease
- Awarded: 2015
- Award Type: Targeted: Whole-Genome Analysis for Autism Risk Variants
- Award #: 385330
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Greg Cooper, Ph.D.
HudsonAlpha Institute for Biotechnology
Structural variation and the genetic architecture of autism
- Awarded: 2015
- Award Type: Targeted: Whole-Genome Analysis for Autism Risk Variants
- Award #: 385035
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Evan Eichler, Ph.D.
University of Washington
Extending autism risk locus discovery to the noncoding genome
- Awarded: 2015
- Award Type: Targeted: Whole-Genome Analysis for Autism Risk Variants
- Award #: 385110
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Matthew State, M.D., Ph.D.
University of California, San Francisco -
Stephan Sanders, B.M.B.S., Ph.D.
University of California, San Francisco -
A. Jeremy Willsey, Ph.D.
University of California, San Francisco -
David Goldstein, Ph.D.
Columbia University -
Nenad Sestan, Ph.D.
Yale University