Department of Health and Human Services


Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)
National Eye Institute (NEI)
National Heart, Lung, and Blood Institute (NHLBI)
National Human Genome Research Institute (NHGRI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute on Drug Abuse (NIDA)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of General Medical Sciences (NIGMS)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Nursing Research (NINR)
National Library of Medicine (NLM)
National Institute on Minority Health and Health Disparities (NIMHD)
National Center for Complementary and Alternative Medicine (NCCAM)
Office of Strategic Coordination (Common Fund)

Funding Opportunity Title

BD2K-LINCS-Perturbation Data Coordination and Integration Center (DCIC) (U54)

Activity Code


U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices

  • January 10, 2014 - See Notice NOT-GM-14-102. Notice of National Institute of General Medical Sciences (NIGMS) Participation
  • December 19, 2013 - See Notice NOT-HG-14-015. Notice of Applicant Information Webinar.
  • December 6, 2013 - See Notice NOT-NR-14-003. Notice of National Institute of Nursing Research (NINR) Participation.

Funding Opportunity Announcement (FOA) Number

RFA-HG-14-001

Companion Funding Opportunity

RFA-RM-13-013; RFA-HG-13-009

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.172; 93.121; 93.846; 93.213; 93.839; 93.838; 93.837; 93.233; 93.866; 93.847; 93.307; 93.399; 93.396; 93.395; 93.394; 93.393; 93.310; 93.173; 93.867; 93.113; 93.856; 93.855; 93.242; 93.273; 93.853; 93.879; 93.279; 93.286; 93.361

Funding Opportunity Purpose

This FOA seeks applications to develop a data coordination and integration center (DCIC) that will address the opportunities and challenges provided by two major NIH efforts: Big Data to Knowledge (BD2K) and the Library of Integrated Network-Based Cellular Signatures (LINCS).  The NIH expects that this BD2K-LINCS DCIC will focus on perturbagen-response data and signatures while ensuring that the resulting resources are effectively utilized by the community by addressing challenges related to biomedical Big Data. A successful DCIC will ensure consistent annotation of data and tools generated within the LINCS program; incorporate (without replicating databases) relevant non-LINCS perturbation data into the LINCS resource; support integration of relevant data, signatures, and tools to allow for seamless exploration of the (LINCS) program’s output by a broad range of biomedical researchers; support linkages to outside knowledge bases, data portals, and resources; support training in perturbation-data science skills; build innovative access and query tools to disparate databases hosting multiple data types; and disseminate the resulting tools and resources to the broad range of biomedical researchers. Related FOAs of relevance to the DCIC include RFA-RM-13-013 soliciting applications for LINCS data and signature generation and RFA-HG-13-009 soliciting applications for BD2K Centers of Excellence.

Key Dates
Posted Date

December 4, 2013

Letter of Intent Due Date(s)

February 19, 2014

Application Due Date(s)

March 19, 2014   

AIDS Application Due Date(s)

March 19, 2014 

Scientific Merit Review

July 2014  

Advisory Council Review

September 2014

Earliest Start Date

November 2014

Expiration Date

March 20, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. See NOT-OD-13-075 and  NIH’s Applying Electronically website for more information.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description


Purpose

The purpose of this funding opportunity announcement (FOA) is to establish a BD2K-LINCS-Perturbation  Data Coordination and Integration Center (DCIC).  The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program with the goal of generating large-scale data sets and signatures that describe human cellular responses to different types of perturbations.  The Big Data to Knowledge (BD2K) initiative is a new trans-NIH initiative that focuses on the challenges of undertaking data science using large and/or diverse datasets.  The goal of the DCIC is to:

As mentioned above, LINCS is an NIH Common Fund program that through the related FOA, RFA-RM-13-013, is expected to establish three to five LINCS Data and Signature Generation Centers (DSGC), which will generate perturbagen-response data, produce relevant cellular signatures from these data, and make these data and signatures available to the research community.  NIH expects that enabling effective community access to the DSGC resources, e.g., by building an integrated knowledge environment, the DCIC will provide the biomedical research community novel ways to extract and build new understanding about the functional relationships among the responding cellular components and consequent cellular and organismal phenotypes.  There are many challenges and opportunities involved in making the perturbation-type data maximally useful as a community resource. These include finding new ways to integrate such perturbation-response data with each other and with other biomedical datasets available in the public domain, developing innovative solutions to providing coherent access to such data and helping support reproducibility of data and analytical results.  Such data science questions are increasingly relevant and critical across the entire biomedical research enterprise, thus forming one of the major aspects of modern biomedical research.  The Big Data to Knowledge (BD2K) initiative is a new trans-NIH initiative that focuses on the challenges of undertaking data science using large and/or diverse datasets.  Multiple initiatives, workshops, etc. are being developed within the purview of BD2K and these can be found at http://bd2k.nih.gov.  Given the common themes and challenges between the aim of establishing a community resource like LINCS and building out novel and innovative solutions to handling data, software, and tools—the aim of BD2K—the NIH has issued this FOA as a joint effort between the two programs to stimulate and enable effective synergies.

Background

This FOA is a joint initiative between the NIH Common Fund LINCS and the trans-NIH Big Data to Knowledge (BD2K, http://bd2k.nih.gov/) program.  The goals of these two efforts are summarized below.

LINCS supports high-throughput data collection, cellular signature generation, and integrative computational analyses of these cellular signatures and makes these tools and resources available to the research community (http://lincsproject.org).  Through distributed databases supported by consistent metadata annotations, LINCS incorporates a new approach to addressing the challenge of integrating, visualizing, and computing across diverse data types from different types of human cells reflecting multiple tissues.

The long-term goal of the BD2K Initiative is to support the necessary advances in data science, other quantitative sciences, policy, and training to support the effective use of Big Data in biomedical research.  For BD2K purposes, the term “biomedical” is used in the broadest sense to include biological, biomedical, behavioral, social, environmental, and clinical studies that relate to understanding health and disease.  The BD2K effort aims to address major obstacles facing biomedical researchers:  locating data and software tools, using standards and metadata, organizing, processing, and analyzing big data sets and effectively sharing data.  The BD2K initiative is currently in the process of establishing “Centers of Excellence for Big Data Computing in Biomedical Sciences” via RFA-HG-13-009.  Other related BD2K efforts that the DCIC via this FOA will work with are future initiatives supporting the outcome of various workshops being organized (see http://bd2k.nih.gov/workshops.html)

The pilot phase of the LINCS program successfully met its goals, and the resources, data, and tools developed during the pilot program are available at http://lincsproject.org.  NIH has issued a new FOA, RFA-RM-13-013, that solicits applications for a new set of perturbation-based LINCS data and signature generation centers (DGSCs).  In the pilot phase, LINCS piloted solutions to a number of problems associated with large, heterogeneous datasets, e.g., moving computations to the data instead of downloading data (cloud computing), standardizing metadata annotations across diverse data types, and providing provenance for data and results by linking back from publication figures and tables to primary data and associated analytical tools.  With the new DGSC program, the challenges associated with annotating, integrating, and analyzing perturbational data like those generated in the LINCS program and others are expected to expand in scope and complexity becoming akin to the big data science that the BD2K initiative is addressing on a broader scale.  Therefore, both the LINCS and BD2K programs are supporting this parallel FOA to solicit applications for a BD2K-LINCS-Perturbation DCIC that will address computational, analytical, and community access challenges, including managing, annotating, and accessing large volumes of disparate data, providing unified access to distributed databases, developing and providing innovative analytical and visualization tools for new data types, coordination of diverse and distributed software and analytical tools to the community, data and results provenance.

Objectives of this Research Program

The BD2K-LINCS-Perturbation DCIC will be expected to address significant data science challenges associated with perturbagen-response datasets to enable important advances in our understanding of cellular function and its relationship with disease and normal biology.  NIH expects that the datasets generated within the LINCS program will act as a core for the DCIC projects since it is consistently generated, based on standard SOPs, and there is a programmatic commitment to deep metadata annotations.  In addition to undertaking computational and algorithmic work the DCIC will also address data science challenges specifically related to providing a uniform and coordinated access to the scientific community distributed databases (primary focus here being the databases created in the LINCS program by the pilot and DSGCs established by RFA-RM-13-013) that hold a large diversity of data types, signatures, and tools to access them. 

As indicated above, the main aim of LINCS is to create a community resource and to undertake outreach efforts to multiple scientific communities, especially in domains where such approaches have not yet been commonly adopted.  NIH is addressing the two main tasks of creating such a LINCS resource that include (1) generating perturbation-response data and associated signatures for each data type and (2) supporting associated innovative data science research, using two separate FOAs, RFA-RM-13-013 and this one, respectively.

To understand the objectives of this FOA (RFA-HG-14-001), it is important to appreciate the details of this and the companion LINCS FOA (RFA-RM-13-013) and anticipate how the grants made as a consequence of the two FOAs will work together.  The LINCS pilot program will conclude by summer 2014, however, an appreciation of the new DSGCs can be gained by examining the data and signatures generated in the pilot phase; see http://lincsproject.org.  To summarize, the companion LINCS FOA (RFA-RM-13-013) will result in the support of 3-5 new LINCS Data and Signature Generating Centers (DSGC) that will comprise a research effort across a wider and more diverse scientific scope than the LINCS pilot centers by supporting a broader and more informative range of cell types, perturbations, and cellular responses (assays).  Each DSGC will be responsible for generating one or a few data types, analyzing the data to build signatures, and providing access to the data, metadata, signatures, and SOPs via its own database.  Each DSGC will also be responsible for building software and analytical tools to provide access to its own data and signatures.  All of the DSGCs are then expected to work closely with each other, with the DCIC, and with NIH staff to provide an integrated user experience for all of the LINCS data. The primary responsibility of building the knowledge environment leading to such an integrated user experience is with the DCIC.  Applicants are encouraged to read RFA-RM-13-013 and review present LINCS data at http://lincsproject.org for more details.

A. Integrated Knowledge Environment.

To meet the goals of this FOA, the LINCS program, and the BD2K initiative, NIH anticipates that innovative data science approaches to integrated access, querying, visualization, and analysis of LINCS and LINCS-like perturbation-response data, signatures and tools would be essential.  Unified access would support an integrated knowledge environment that can be used to obtain access and use perturbation-response data and signatures to facilitate the research aims of many groups across  the broad biomedical research community.

Since each LINCS Data and Signature Generation Center (DSGC) will have capacity for management of its own data and signatures and the infrastructure and analytical capability to support the ability of the community to run queries on its own data, the activities of the DCIC will be mainly focused on data integration and capability to seamlessly query across diverse data and signature sources across all DSGCs and other related data sources outside the LINCS consortium.  Such seamless queries should accommodate different database and software interfaces.  The DCIC should not simply duplicate the functions of any existing public databases (e.g., GEO, OMIM, NIF, TCIA, UniProt, HMDB).

NIH anticipates that the pilot LINCS data (see http://lincsproject.org) and access methods, APIs, and other tools can be used as a template to guide proposed innovative solutions and approaches for this FOA.  While innovative new solutions are encouraged, so is building upon existing open-source community tools or projects. It is also critical, however, to maintain flexibility and innovation both in the types of data science research undertaken during the course of this project as well as software engineering approaches that will be adopted.  Such flexibility is essential given the uncertainty regarding the data types that will be the core part of LINCS DSGCs and rapidly evolving pace of science in the field.  However, given the constraints of scale and data quality for the DSGCs, the range of data types will be constrained and many of these data types can be scientifically anticipated in the DCIC application.  A suitably robust and flexible approach should be able to adapt to incorporate new, diverse data types.

Innovative solutions in enabling a knowledge environment including the associated software, technical, infrastructural solutions, are clearly necessary for a DCIC.  Other essential features of the knowledge environment would include scientifically meaningful metadata annotations, and visualization and analytical tools to support multiple types of data integration activities.  The data sources supporting the knowledge environment should include datasets and signatures from funded DSGCs, the pilot LINCS data and signatures, and other data and tools relevant to LINCS programmatic goals (see RFA-RM-13-013).  The data should be presented through a user-friendly web-interface, and the DCIC should address the needs of both the typical biomedical researcher and the expert computational researcher in accessing and using LINCS resources.  Flexibility in the implementation plan including for the single-user interface is crucial, as the DCIC implementation plan may be adjusted after award to accommodate the approaches and data from the DSGCs that will be funded after the DCIC application is due.  The web-interface built and maintained by the DCIC will also be the public face of the entire LINCS program, so professional design and software elements should be incorporated. In addition, it would be useful to provide the community with useful summaries of the content of the LINCS and related resources available for querying and browsing.  The DCIC will build an integrative knowledge environment that will be used to advance the understanding of the interconnections between mechanism-based associations, as defined by the signatures describing the response to disparate biological perturbations in diverse cell types.  To that end, the DCIC is expected to conduct research and development of approaches, methods, software, tools, and other resources relevant to LINCS-type perturbagen-response data to enable management (e.g., approaches for developing efficient querying of distributed databases storing diverse data types, suitable data and metadata formats, standards, ontologies, and as relevant, interoperability, etc.), processing, and annotation. Development of novel methods of visualization, statistical and computational analysis, simulation, and modeling as applicable for generating an integrative understanding and classification or predictions of perturbation datasets would be core data science research areas for the DCIC. The main aim of the data science research should be to enhance the value of the LINCS resource and other perturbation-type public domain data for a broad segment of the biomedical research community.

A1. Data Integration.  Data integration is a substantial data science challenge.  In the particular case of the LINCS program, data integration critically involves relating perturbation readouts within and across data and signature types, including additional knowledge from non-LINCS sources to make the LINCS resources more valuable and useful.  In integrating non-LINCS data to other types of data it might be useful to consider other relevant data science challenges, such as those associated with multiplatform data (desktop, cloud-based storage, etc.) or data with special considerations (e.g., sparse data, heterogeneous data, or very large or very small datasets), or efficient access of distributed databases serving different data types. The utility of other, non-LINCS community resources could be key in undertaking a number of data integration tasks, e.g., knowledge of disease interconnections may be extracted and synthesized from information sources such as existing public databases (GEO, Peptidome, dbGaP, Protein Expression Purification and Crystallization DataBase [PepcDB], and Human Gene Mutation Database [HGMD], etc.) and published literature.  NIH recognizes that the DCIC application will be written in the absence of information about the DSGCs that will form the new LINCS consortium. This can be challenging. Scientifically, one way to address it is by utilizing the LINCS pilot datasets (both the pilot U54 data generation centers and the technology development U01 centers) and other public domain datasets as exemplars to describe the types of data integration algorithms that would be built along with detailed description of the general guiding principles on collaborations with DSGCs that could have newer data types.

A2. Collaborative Environments and Technologies.  NIH anticipates that novel data science challenges will have to be addressed in providing an integrated access to LINCS and other pertubation data resources to the broader scientific community.  One aspect of this challenge is how to engage and provide access to LINCS perturbagen-response data and tools to a diverse user community that includes biomedical researchers, computational experts, and big data scientists.  Potential solutions may include (but are not limited to) proposing knowledge environments or research commons; scalable, extensible, and maintainable methods of data and metadata curation; novel and robust approaches of data attribution and provenance; and support LINCS analysis using external data sets.

A3. Support Unified Access to LINCS DSGC Resources.  The success of the project requires the DCIC to work with the DSGCs to provide unified access to the LINCS-related data, signature, and tool resources to the user community through a web portal or by other methods.  The user community is expected to encompass both typical biomedical researchers and expert computational scientists, each of whom has different needs and requirements for data and signature access.  A core scientific requirement for the DCIC would be to enable a LINCS user to execute scientifically feasible queries on the entire LINCS matrix.  One way to support this could be by executing queries simultaneously on the local data at all DSGCs using the DSGC-supplied Application Programming Interfaces (APIs) and then building a coherent representation of the results for presentation.  NIH understands that this is another challenging part of the application since the DSGC APIs are not available to the DCIC applicant.  The scientific challenge can be met by describing the best software design to achieve these goals along with a description of suitable backup plans as well as principles of collaboration with the DSGC and the LINCS consortium to achieve this overall aim.  These requirements on the DCIC does put some constraint on the range of software and other choices for each DSGC, such that each DSGC may need to develop a number of core simple visualization elements that can be used under different conditions.  The DSGC, in turn, are expected to anticipate the need for the DCIC and adopt suitable software strategies. The DCIC will be responsible for coordinating implementation of such unified queries, visualizations and access across the DSGCs..

B. Data Science Research Collaborations.

To help ensure that the data science research carried out meets the overall goals of both the LINCS program and the BD2K initiative it is essential to consider the DCIC as an enabling community resource project.  The most challenging big data science topic this program must address is data integration, therefore the DCIC will carry out a data science research projects to address data integration.

Some examples of data science research projects include, but are not limited to, the following:

B1. Internal Data Science Projects. NIH expects that the DCIC will undertake innovative data science research.  It is expected that these projects will be designed flexibly to adapt to changing requirements of including new data types from the LINCS DSGCs and other public domain datasets during the course of the project period.

B2. External Data Science Collaborations. In addition, the DCIC will support several specific, short-term data science research collaborations.  These collaborations must be relevant to supporting the overall goals of the LINCS and BD2K initiatives.  It is expected that each of these data science research projects will involve collaborations with non-LINCS funded researchers.  

C. Consortium Coordination and Administration

The DCIC is expected to perform as an administrative coordinating center for the LINCS program and also to participate actively within the BD2K Centers Consortium (RFA-RM-13-013).  NIH anticipates that such administrative coordination will form an important component of the DCIC.

C1. Support Incorporation of LINCS-related Data Types from External Resources.  It is expected that each DSGC will act as an active resource for its chosen data type(s) within the LINCS program.  As such, each DSGC is expected to generate data and signatures for its data type for LINCS, and also to identify relevant, high quality, non-LINCS data sets that might be incorporated into the knowledge environment established by the DCIC.  Inclusion of such external resources will help connect LINCS data resources to other research efforts and expand the scope and relevance of the LINCS resource.  Examples for gene expression data that the applicant may propose might be a suitable subset of GEO as a source relevant for non-LINCS gene expression data or ImmGen (Immunological Genome Project) for gene expression in the immunological system.  The DCIC will collaborate with the DSGCs and relevant external partners to determine the best approach to incorporate these outside datasets into the LINCS knowledge environment.  The overall aim is to enable scientific queries across datasets generated at multiple locations through the LINCS knowledge environment and not to replicate existing databases.  NIH understands that the DCIC applicant will be unaware of the DSGC specific aims at the time of the application and as such specific approaches in how to achieve such incorporation will necessarily have to have some imprecision. T his will be one of the major activities of the LINCS consortium and is a joint responsibility of the DCIC and DSGC (see RFA-RM-13-013) as part of the U54 cooperative agreement.

C2. Coordinate Annotation of Data, Tools, and Resources.  Useful data and metadata standards are crucial for generating LINCS signatures that can be easily used by the community, as well as in meeting data integration needs.  An important goal of the LINCS program is to promote a culture where a large body of annotated and shareable data and analytical tools is available online for use by the broad biomedical research community.  The DCIC is responsible for ensuring consistency among the annotations of the different DSGCs of the data, experimental protocols, signatures, tools, and consistency with community best practices by leveraging other standards appropriately and by developing a set of core use-cases that the metadata annotations will support.

D. Community Training and Outreach.

The DCIC, together with the DSGCs, will be responsible for engaging the biomedical and data science research communities on behalf of the LINCS program.  This will include assisting in coordinating outreach and training efforts arising from the individual DSGCs; the DCIC may also carry out in its own (additional) LINCS community outreach and training activities primarily focused on Big Data challenges in handling and analysis of perturbation-type data.  The DCIC will also coordinate all collaborative research opportunities with the research community and the LINCS program as a member of the LINCS U54 cooperative agreement.

D1. Coordinate LINCS and BD2K Community Outreach and Training Opportunities.  The DCIC will provide informatics and analysis training and outreach activities consistent with its research aims and goals, and will coordinate the individual DSGCs’ training and outreach activities.

D2. Access to LINCS Resources.  Establishing the LINCS resource and approach within the biomedical community may in turn require careful consideration about differing requirements for different sub-communities.  Therefore choices may have to be made to identify core functionalities that would be broadly usable and include only high-value adaptations for specific smaller communities.  The NIH anticipates that specific attention to the scientific needs of these smaller communities would need careful planning and cost-benefit considerations.  Thus, part of the DCIC’s outreach effort could be to determine whether or not specific communities need specific tools or resources or might prefer to have API access to their own portals and potentially through collaborative projects enable such access.  Such access could include support for the development of new types of analyses; building and validating improved algorithms for signature generation; building cell-type specific biological networks, among others.  Creative solutions, either cloud-based or other data access alternatives dictated by the size and complexity of the datasets, are encouraged.  Careful thought should be given to any special obstacles that might be faced and options to address them, such as very large data sizes that may make downloading multiple copies of datasets impractical.  Training workshops for beginning researchers on LINCS resources and tools is an approach that the LINCS pilot program has found to be effective. Approaches like workshops, hackathons, or challenges can also be useful.  The applicant should balance the different requirements and propose creative solutions.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

The OER Glossary and the PHS 398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIH intends to fund 1 award, corresponding to a total of $5,000,000, for fiscal year 2015.  Future year amounts will depend on annual appropriations.

Award Budget

Application budget may be up to $3 million direct costs per year, not including the F&A costs of subcontracts.

Award Project Period

The total project period for an application submitted in response to this funding opportunity may be up to five years.      

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

Higher Education Institutions

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are  allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS 398 Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility


Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information


1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

The letter of intent should be sent to:

Jennie Larkin, Ph.D.
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute (NHLBI)
6701 Rockledge Drive Rockledge 2, Room 8200
Bethesda, MD 20892-7940
Telephone: 301-435-0513
Fax: 301-480-1454
Email: lincsproject@mail.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Page Limitations

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, in addition to the following page limitations to the Research Strategy section of each component of the application.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the PHS 398 Application Guide, and should be used for preparing a multi-component application.

The application must consist of the following components:

Overall Component

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Overall)

All instructions in the PHS 398 Application Guide must be followed.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Overall)

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Overall)

All instructions in the PHS 398 Application Guide must be followed.

Detailed Budget for Initial Budget Period (Overall)

All instructions in the PHS 398 Application Guide must be followed.  In addition, provide the total budget for the initial budget period for the entire Center application, by summing the individual budgets of each of the components (Integrated Knowledge Environment, Data Science Research Collaborations, Consortium Coordination and Administration, and Community Training and Outreach, including sub-contracts); i.e., the budget presented in the Overall Component should be the cumulative budget for the entire BD2K-LINCS-Perturbation DCIC.   

Budget for Entire Proposed Period of Support (Overall)

All instructions in the PHS 398 Application Guide must be followed . In addition, provide the total budget for the entire proposed period for the entire Center application, by summing the individual budgets of each of the components (Integrated Knowledge Environment, Data Science Research Collaborations, Consortium Coordination and Administration, and Community Training and Outreach, including sub-contracts); i.e., the budget presented in the Overall Component should be the cumulative budget for the entire BD2K-LINCS-Perturbation DCIC.  

Biographical Sketch (Overall)

All instructions in the PHS 398 Application Guide must be followed.

Resources (Overall)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims: The Specific Aims for the Overall Component should be the overall vision for the Center.  These Specific Aims should not be the same as the specific aims of the other components, but should be overarching and at a high level.

Research Strategy:  The Overall Component should provide a concise vision and proposed plan for the Center.  What scientific challenges are being addressed, what approaches, methods, software, and tools will be generated, who are the users, and how will the Center be useful?  The Overall Component should also include a concise description of the structure of the Center, including a brief management plan and organization chart.

The Overall Component should explain how the individual components of the center including key personnel, will interact.  Clearly explain the guiding principles of the interaction, including software design activities, with the LINCS Data and Signature Generation Centers, the BD2K Centers of Excellence for Big Data Computing in the Biomedical Sciences and other community interaction efforts.  The application should describe all necessary expertise and approaches to support meaningful data integration, provision of collaborative environments, and development of necessary innovative technologies.

Resource Sharing Plan:Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

The resource sharing plan for the Overall Component should cover all the activities of the Center. Program Staff may negotiate modifications to these plans prior to funding.  Plans are expected for sharing software (see below).

Consistent with achieving the goals of the program, NIH expects that the project datasets, including Standard Operating Procedures (SOPs), as relevant, model and software be widely shared with the scientific community for research, as much as possible.  BD2K-LINCS-Perturbation DCIC awardee is expected to release to the research community data, models, and software in a timely fashion through an informatics platform and other standard mechanisms.  It is expected that raw data, as well as processed data along with relevant signatures be made available to the community, as appropriate, via existing public databases or specialized resources generated for this project.  The development of policies, methods, and standards for such sharing is critically important for LINCS and BD2K programs.  The NIH expects that the DCIC awardee will develop such policies, methods, and standards in concert with the NIH and the LINCS Steering Committee and Working Group.  These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing.

Specific Plan for Sharing Software:  A software dissemination plan, with appropriate timelines, is expected to be included in the application.  There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact.  Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan.  A dissemination plan guided by the following principles is thought to promote the largest impact:

Integrated Knowledge Environment

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Integrated Knowledge Environment)

All instructions in the PHS 398 Application Guide must be followed.  

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Integrated Knowledge Environment)

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Integrated Knowledge Environment)

All instructions in the PHS 398 Application Guide must be followed.

Detailed Budget for Initial Budget Period (Integrated Knowledge Environment)

All instructions in the PHS 398 Application Guide must be followed.

Budget for Entire Proposed Period of Support (Integrated Knowledge Environment)

All instructions in the PHS 398 Application Guide must be followed.

Biographical Sketch (Integrated Knowledge Environment)

All instructions in the PHS 398 Application Guide must be followed.

Resources (Integrated Knowledge Environment)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Integrated Knowledge Environment)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims: This section should include the Specific Aims of the Integrated Knowledge Environment component.

Research Strategy:  This is an important goal and deliverable for the DCIC and forms the core of how the community will access and utilize the data, algorithms, results from the scientific efforts of the entire LINCS program including both the DSGC and the DCIC. From a BD2K perspective, it focuses on developing novel methodlogies for integrating disparate and diverse databases within one query and analytical environment. From the LINCS perspective, the Integrated Knowledge Environment will be the practical realization of these novel methodologies. Within this U54 cooperative agreement the DCIC will have flexibility in working with the LINCS DSGCs to deliver such an integrated knowledge environment. The applicant should demonstrate experience in building software tools that integrate different databases using API and other related modern software engineering practices as well as identifying and anticipating specific challenges, and outlining suitable approaches to solutions.

The applicant is expected to identify specific non-LINCS databases and portals available to the community that contain scientifically related datasets supplementing (e.g., gene expression databases) or complementing (e.g., ENCODE or pathway information to address data integration) and how these will be used within the Integrated Knowledge Environment.  The applicant should identify existing open-source analytical and visualization tools that would be utilzied to build the knowledge environment, or how such resources might exchange information with the knowledge environment.  It is not expected that the DCIC will replicate these other data sources, however, suitable summaries can be extracted and stored locally within the DCIC to enable responsive support of queries and other analytical tools. In this context, as described above, the applicant is encouraged to use the LINCS pilot datasets (both U54 and the smaller datasets generated by the Technology Development U01's, see http://lincsproject.org) to provide specific scientific details. Flexibility in adapting to new datatypes is also critical for a successful DCIC.

The applicant should also demonstrate experience and capabilities in designing tools for visualization of complex scientific data. The specific aims should detail the types of scientific questions assuming the LINCS pilot data and other relevant resources already available that would be supported using the infrastructure of the Integrated Knowledge Environment.  In addition the applicants should outline how new data types and related analytical challenges will be met during the project period.  The application should provide a detailed research strategy for developing this knowledge base, including strategy, approach, milestones, and should describe how coordination challenges with the DSGCs will be approached, and any alternative plans to ensure success.

Data Integration: Applicants should propose to develop efficient and meaningful ways to create connections across LINCS perturbagen-response data and signature types (i.e., data integration), or between LINCS data and other perturbation or relevant sources to advance our understanding of the best use of perturbation studies.  While it is not expected that all data integration challenges will be addressed in a single application, it is crucial that applicants provide a scientific rationale for identifying the most relevant scientific challenges and their proposed innovative solutions.  The applicant should describe in silico experimental design in detail and demonstrate relevant capabilities, such as biological data mining, text mining, integration of multiple variables over multiple biological scales, computational modeling and simulation of biological processes, and presentation of data and knowledge through interactive web-interface.

Support Unified Access to LINCS DSGC Resources:  The interaction between the DSGCs and the DCIC is crucial for the success of bui,ding a unified access to LINCS resources.  While the DCIC is expected to facilitate access to tools generated by each DSGC, it is expected that each DSGC will develop and make available tools relevant to the assays proposed by the DSGC.  The DCIC should provide a plan to manage and coordinate access to the LINCS data and resources.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Applicants are instructed to place the Resource Sharing Plan only in the Overall Component.

Data Science Research Collaborations

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Data Science Research Collaborations)

All instructions in the PHS 398 Application Guide must be followed.  

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Data Science Research Collaborations)

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Data Science Research Collaborations)

All instructions in the PHS 398 Application Guide must be followed.

Detailed Budget for Initial Budget Period (Data Science Research Collaborations)

All instructions in the PHS 398 Application Guide must be followed with the following exceptions: It is expected that the DCIC will set aside $700,000 in direct costs each year to support External Data Science Collaborations. 

Budget for Entire Proposed Period of Support (Data Science Research Collaborations)

All instructions in the PHS 398 Application Guide must be followed with the following exceptions: It is expected that the DCIC will set aside $700,000 in direct costs each year to support External Data Science Collaborations. 

Biographical Sketch (Data Science Research Collaborations)

All instructions in the PHS 398 Application Guide must be followed.

Resources (Data Science Research Collaborations)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Data Science Research Collaborations)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims: This section should include the Specific Aims of the Data Science Research Collaboration.

Research Strategy:  There are two parts to this important component: internal and external data science projects.

Internal Data Science Projects:  In this part, the applicants are expected to propose an outline of their internal research aims for data science with a focus on perturbation-type experimental data including how these analytical tools will be deployed for community use in the Integrated Knowledge Environment.

External Data Science Collaborations: In this part, the applicants are expected to identify three collaborative projects (to last 12 to 15 months) with groups that are not part of the application to utilize this set aside.  The major intent of these projects are to engage with the community to develop novel tools for big data science that use perturbation-type data as the major focus.  NIH expects that a process or plan will be defined by the DCIC to identify future research collaboration projects on a yearly basis.  This plan may be modified after award in consultation with NIH LINCS Working Group.  To allow a wide variety of collaborative projects during the lifetime of the DCIC award, effective turnover of supported projects is crucial and as such identifying appropriate metrics for evaluation is essential.  The overall LINCS Steering Committee will make recommendations to the NIH LINCS Project Team on suitable external scientific review and ranking of all subsequent proposed collaborative projects.  

The DCIC is expected to administer funds to support these collaborations in each year of the project.  The DCIC will oversee the review and award of collaboration project funds and coordinate the submission of progress reports by the awardees for review by program staff.  The applicant should plan to utilize the LINCS External Scientific Panel as the peer review panel for future (Year 2 and beyond) collaborative projects.  The DCIC will be responsible for solicitation of applications for the collaborative projects through websites, list-serves and other appropriate means.  These collaborations are meant to involve the community into LINCS efforts, to bring in novel expertise and analytical capabilities, to engage in high-risk high-reward approaches within this dynamic field.  These collaborative projects should be of limited duration, should be milestone driven and require clearly identified methods to end them if they are not likely to succeed at the end of the first year of the award.  As the LINCS and BD2K resources and programs develop, it is anticipated that new opportunities will arise that will need additional expertise from outside the Consortium or require new collaborations with other members of the Consortium.  The specific aims of each of these collaborations should be delineated along with metrics for evaluation and budget in this section of the aplication.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Applicants are instructed to place the Resource Sharing Plan only in the Overall Component.

Consortium Coordination and Administration

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Consortium Coordination and Administration)

All instructions in the PHS 398 Application Guide must be followed.  

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Consortium Coordination and Administration)

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Consortium Coordination and Administration)

All instructions in the PHS 398 Application Guide must be followed.

Detailed Budget for Initial Budget Period (Consortium Coordination and Administration)

All instructions in the PHS 398 Application Guide must be followed with the following excetions: Applicants may request up to $100,000 per year for coordination efforts with BD2K Centers and BD2K Consortium activities.  Such funds may be used to support attendance at BD2K Centers Investigator meetings, travel of DCIC staff to visit other BD2K Centers for collaborative activities, participation in the BD2K Centers Steering Committee, or other proposed activities that would support fruitful data science collaborations with the BD2K Centers program.

Budget for Entire Proposed Period of Support (Consortium Coordination and Administration)

All instructions in the PHS 398 Application Guide must be followed with the following excetions: Applicants may request up to $100,000 per year for coordination efforts with BD2K Centers and BD2K Consortium activities.  Such funds may be used to support attendance at BD2K Centers Investigator meetings, travel of DCIC staff to visit other BD2K Centers for collaborative activities, participation in the BD2K Centers Steering Committee, or other proposed activities that would support fruitful data science collaborations with the BD2K Centers program.

Biographical Sketch (Consortium Coordination and Administration)

All instructions in the PHS 398 Application Guide must be followed.

Resources (Consortium Coordination and Administration)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Consortium Coordination and Administration)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims: This section should include the Specific Aims of the Consortium Coordination and Administration component.

Research Strategy:  Applicants are encouraged to describe special or unique strengths that may be relevant to Consortium infrastructure and research.  Examples could include significant previous experience coordinating research projects, prior participation in research funded by an NIH cooperative agreement, prior development of award-winning media programs to disseminate information about research to the public, or state-of-the art biomedical or research informatics systems (e.g., innovative tools, methods and algorithms), which may be shared or may be available to develop and expand scientific productivity of the Consortium.  The DCIC can use the current LINCS (pilot) datasets as templates to propose approaches and computational methodologies to identify and incorporate relevant external datasets into the LINCS resource.  If the pilot data are used, the application should discuss how those efforts could act as a test bed for incorporating newer resources based on the data types that will be part of new DSGC.

The DCIC should describe a plan to work across the LINCS Consortium to ensure consistency of annotations across the different DSGCs for the data, protocols, signatures, tools.  It is also responsible for coordinating the tracking of use of the different LINCS data and resources across all the DSGCs and build consolidated statistics.  The DCIC will also provide logistical support to DSGCs for their various Community Interaction Projects (see RFA-RM-13-013).  Note however that, each DSGC is responsible for proposing development and use of data and metadata standards to annotate their data and signatures, and to adopt existing community standards that are most relevant for their application and to perform the actual annotation.

Coordination with LINCS. The DCIC will coordinate activities across the LINCS Consortium, including (1) supporting LINCS consortium activities including any working groups that may be formed; (2) stewarding consortium-wide recommendations on policies, standards, and quality control activities; and (3) coordinating consortium-wide manuscript and other document preparation.

In addition, the DCIC will be responsible (along with suitable partners from the DSGCs) for providing LINCS-specific input into the various BD2K workshops and initiatives, as well as adopting relevant standards and resources established by various BD2K initiatives.

Coordinate with BD2K.  As the LINCS and BD2K programs will fund the DCIC it is expected to actively participate in the BD2K Centers of Excellence Consortium (see RFA-HG-13-009 for details).  The application should provide plans for coordination efforts with BD2K Centers and BD2K Consortium activities including attendance at BD2K Centers Investigator meetings, travel of DCIC staff to visit other BD2K Centers for collaborative activities, participation in the BD2K Centers Steering Committee, or other proposed activities that would support fruitful data science collaborations with the BD2K Centers program.

The application should include a statement indicating willingness to engage in collaborative activities across the Consortium, in partnership with relevant NIH staff, to support the goals of the LINCS and BD2K programs, and to accelerate translation of study findings to the scientific community.

Administrative Plan: The application should describe the management and integration of activities in the Center.  Applicants should specify appropriate administrative/business management staff, as well as the oversight mechanisms that will be used by the Center Director (PD/PI), any Center Co-Directors, and any other relevant key personnel.  If multiple geographic sites are involved in the proposed Center, the Administrative Plan should describe the leadership and communication plans to manage the multiple sites.  The applicant should describe the proposed Center structure and the application may include an organizational chart.

Assessment of Progress:  The Administrative Plan should describe a set of milestones or defined objectives that the PD/PI and NIH staff can use for annual assessments of whether the proposed research and other activities of the Center are progressing appropriately toward the goals of the Center.  NIH recognizes that some basic research accomplishments may not be easily quantifiable; thus, the PD/PI should propose appropriate criteria to measure the progress of the research.  The proposed milestones or objectives for the out-years may be less detailed than those for the first year of the project.  Since the award uses the Cooperative Agreement mechanism, a set of Center milestones or objectives will be negotiated with program staff prior to the award.  Similarly, a set of overall milestones or objectives for the LINCS and BD2K programs will be negotiated after the award.  Progress toward the milestones or objectives should be reported annually, and the milestones will be reconsidered, and renegotiated if necessary, as part of the annual non-competing continuation application (Type 5) process.  The list of Center milestones or objectives should be limited to two pages.

Evaluation:  The Administrative Plan should include a plan for evaluating the quality and utility of the Center products and training.  Criteria of evaluation for Center products may include adequacy, trustworthiness, authenticity, integrity, availability, documentation, and transparency. Specific examples of evaluative information could include tracking the number of users, background/training of the users, requests for services, successful use of the Center products, publications citing uses, number of students, use of training materials, the ability to extend the utility of tools through collaborations with other Centers, etc.  The research community being served will have expectations that could be documented through mechanisms such as user feedback, letters of support, etc.  There should be evaluative measures for both short-term and long-term outcomes.  Quantifiable measures of intermediate results and success are important and should be built in as:

Infrastructure:  The DCIC research requires appropriate computer, data storage, and networking infrastructure resources.  The application should describe the infrastructure resources that are available, to be obtained, or will be developed during the award, and justify how these resources will be used to support the research at the host institution as well as the biomedical research community.

Transition Plan:  For the LINCS DSGC active work towards a transition will begin in the fourth year of the Program with the Community Interaction and Outreach component playing an important role in building towards such a transition.  Applicants are expected to provide a transition plan in the application describing approaches that would result in long-term support for the DCIC resources beyond the 5-year funding of this FOA. These plans will likely be modified and improved during the period of award in conjunction with the NIH LINCS and BD2K Working Groups. Applicants are advised to refine their transition plans during the first three years of the award to accommodate other potential mechanisms of support, such as fee for service and/or private funding.

Awardees will be expected to work with NIH to develop tracking and reporting on their data, software infrastructure and tools and the usage of these by the research community.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Applicants are instructed to place the Resource Sharing Plan only in the Overall Component.

Community Training and Outreach

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Community Training and Outreach)

All instructions in the PHS 398 Application Guide must be followed.  

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Community Training and Outreach)

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Community Training and Outreach)

All instructions in the PHS 398 Application Guide must be followed.

Detailed Budget for Initial Budget Period (Community Training and Outreach)

All instructions in the PHS 398 Application Guide must be followed.

Budget for Entire Proposed Period of Support (Community Training and Outreach)

All instructions in the PHS 398 Application Guide must be followed.

Biographical Sketch (Community Training and Outreach)

All instructions in the PHS 398 Application Guide must be followed.

Resources (Community Training and Outreach)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Community Training and Outreach)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims: This section should include the Specific Aims of the Community Training and Outreach component.

Research Strategy:  Community engagement is an important tool for the DCIC to enable dissemination of the proposed resources in the application.

Applicants are encouraged to propose plans for suitable tutorials, webinars, workshops at scientific meetings, development of use-cases or challenges that focus on the use of their uniquely generated data and analytical resources to stimulate use of their resources.  Other community outreach efforts, specifically focused on computational groups, could include organizing focused research competitions, as well identifying and engaging targeted biomedical communities that are well-positioned to utilize the LINCS resources or can utilize the data science tools that are created to fulfill BD2K initiative’s aims and goals.  Organizing workshops in association with major scientific meetings is also encouraged.  Each applicant is expected to identify high quality, relevant non-LINCS data sets that might be incorporated or integrated into the LINCS.  A tabular presentation of the identified resources should be offered. Applicants may propose to leverage major data repositories and domain-specific resources, as best suits their scientific area. Consideration should be given to addressing any special challenges for assessing quality metrics, availability of suitable metadata, or robust algorithms for using non-LINCS data sources.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Applicants are instructed to place the Resource Sharing Plan only in the Overall Component.

Appendix for the Entire Application

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS 398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation.  As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).  These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses.  Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits. 

If selected, appropriate funding will be provided by the NIH Intramural Program.  NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA.  Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights. 

Applicant Information Webinar

An Applicant Information Webinar will be held on January 13, 2014, from 1:00 p.m. to 2:30 p.m. ET to provide information about the FOA to prospective applicants.  NIH staff will provide an overview of the FOA and answer questions.  The webinar is open to all prospective applicants.  Participation in the webinar is not a prerequisite for applying, and is not required for a successful application.  Information about how to participate in the webinar will be posted at http://commonfund.nih.gov/lincs/.  Potential applicants are encouraged to submit their questions or comments to lincsproject@mail.nih.gov prior to the meeting.  Afterwards, the webinar slides and a summary of the questions and answers will be posted on the same site.  NIH will also post a list of Frequently Asked Questions (FAQs) and answers; this information may be updated without additional notice. 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.    

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an impact score for each component of the Center functions (Overall, Integrated Knowledge Environment, Data Science Research Collaborations, Consortium Coordination and Administration, and Community Training and Outreach).  The impact score of the Overall Component is the impact score of the entire application.  Reviewers will provide individual criterion scores for the Overall Component, but not for the other components.  They will also provide written critiques for all the components of the application.

The Overall Center impact score will emphasize a) the overall effectiveness and innovation of the approaches, methods, software, tools, and related resources in integrating and providing access to perturbagen-response data, signatures, and tools generated by the LINCS program and other sources; b) the scientific merit of the proposed data annotation, integration, and analysis plans c) scientific merit of community interactions and outreach activities; c) the qualifications of the Center Director and other staff; d) the quality of the plans for management and coordination of the Center and the LINCS consortium activities, and e) the overall impact of the Center.  The overall impact score for the DCIC application may be higher or lower than the average of the individual components based on assessment of whether the whole is greater than the sum of its components.

Overall Impact - Overall

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Center proposed).

Scored Review Criteria - Overall

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a Center that by its nature is not innovative may be essential to advance a field.

Significance

Does the Center address an important problem or a critical barrier to progress in the field? If the aims of the Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Is the proposed project likely to result in a significant public resource?  Are the proposed sets of queries and tools to provide access to the signatures, data, and tools appropriate, adequate and significant for both typical biomedical researchers and bioinformatics experts?  Have the data integration challenges within and across other existing public resources been adequately addressed?  Are the software approach and choices proposed in the application suitable for the DCIC to create a single user-interface for all LINCS data and signature access?  Are the plans for providing access to the community scalable to support both user-driven and automated queries?  

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?  

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?   

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?  Will the approach result in a resource that can be integrated with other data from the community (e.g., genetic, expression, proteomic, etc. data; small molecules; pharmaceutical research) and across the LINCS program?  Is there a viable plan for coordinating data, signature, and tool access across the LINCS consortium?  Are the plans for the use of standards for data and metadata appropriate for this field?  

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?   

Integration of the Components in the Center

Will the whole Center be greater than the sum of its individual components?  Are the four major functions (Integrated Knowledge Environment, Data Science Research Collaborations, Consortium Coordination and Administration, and Community Training and Outreach) properly coordinated?  

Potential for Collaboration:  Does the applicant demonstrate the ability to work as part of a multi-disciplinary team through significant prior experience in coordinating collaborative scientific research?

Coordination:  Does the applicant demonstrate significant experience coordinating complex research efforts, including logistical support for meetings and calls, data management systems, and the development and archiving of reports and other documents?

Communication:  Does the applicant demonstrate significant experience in development of web sites, training and dissemination programs for research programs, in communication of research results to other scientists, and in communicating scientific principles to the lay public? 

Additional Review Criteria - Overall

As applicable for the Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is  justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations - Overall

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Appeals of initial peer review will not be accepted for applications submitted response to this FOA.

Applications will be assigned  to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information


1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.      

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The Program Director/Principal Investigator will have the primary responsibility for:  defining the details for the projects within the guidelines of this FOA, and for performing all scientific activities.  The PD/PI will agree to accept the close coordination, cooperation, and participation of the NIH staff in those aspects of scientific and technical management of the project as described below.

BD2K Consortium Responsibilities:

The BD2K Centers Consortium:  This includes the set of funded Center awards and NIH BD2K Project Team staff.  The BD2K Center Consortium will rely on collegial and cooperative interactions among its members and with other initiatives that may emerge. 

BD2K Steering Committee (SC):  This is the primary forum of the BD2K Center Consortium.  The PI(s)/PD(s) of the awards and the NIH Lead Science Officers serve on the Steering Committee.  See further details about the Steering Committee under Terms and Conditions Section VI.2.

Each year there will be a BD2K Center Consortium Meeting, which will be held back-to-back with a meeting of the BD2K Independent Experts Committee.  Each Center will present its research findings at this meeting.  There will also be two Steering Committee meetings per year.

LINCS Consortium Responsibilities:

Specifically, the PD/PI of this DCIC center will:

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The LINCS Project Scientists will have the following substantial involvement:

LINCS Working Group Responsibilities.

The LINCS Working Group will serve as the trans-NIH body overseeing and coordinating the activities of all LINCS components.  Working Group membership will include one or more representative(s) from each of the NIH Institutes and Centers (IC) participating in the LINCS program. Program Officials and Project Scientists can be members of the LINCS Working Group.  Each participating NIH IC will have a single vote on the Working Group, no matter how many members from the NIH IC are involved. The Working Group will receive recommendations from the LINCS Steering Committee. The LINCS Working Group will have the following involvement:

Areas of Joint Responsibility include:

LINCS Steering Committee Functions.  The LINCS Steering Committee is the operational group responsible for coordination of the activities of all components of the LINCS.  The LINCS Steering Committee will identify scientific and policy issues that need to be addressed by all components of the LINCS program, develop recommendations to the Working Group for addressing such issues, coordinate the primary recommendations for choice of experimental protocol, and coordinate the dissemination of data, assay protocols, and other materials with the wider scientific community.  The LINCS Steering Committee membership will include the PD/PI of each of the components of the LINCS program, and the Project Scientists including the BD2K-LINCS-Perturbation DCIC. The PD/PI of each center (or designee) will have one vote on the LINCS Steering Committee.  The Project Scientists may vote, but the total votes will count as a maximum of one-third of the total LINCS Steering Committee votes. Membership on the Steering Committee becomes effective upon issuance of the Notice of Award.  The Steering Committee may add additional members if technology development, data generation, coordination, standardization or integration activities will benefit from such an expansion. Other NIH staff may attend the Steering Committee meetings, if their expertise is required for specific discussions.  The LINCS Steering Committee may establish additional subcommittees or workgroups for specific tasks.  No NIH staff member may chair any committee or subcommittee of the Steering Committee.  The LINCS Steering Committee will:

External Scientific Panel (ESP):  The ESP will be responsible for reviewing and evaluating the progress of the LINCS program in meeting their individual and collective milestones and goals, and making recommendations about the progress and directions of the LINCS program and individual components to the LINCS Working Group.  The ESP will be composed of 4-6 senior non-federal scientists who are not directly involved in the activities of the LINCS program. The LINCS Working Group will appoint members to the ESP.  The LINCS Working Group will select one member as chair. The LINCS Project Scientists and LINCS Working Group members may attend the External Scientific Panel meetings as non-voting participants. The ESP will have the following involvement:

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-435-0714
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Ajay Pillai, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-594-7108
Email: lincsproject@mail.nih.gov

Jennie Larkin, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0513
Email: lincsproject@mail.nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Cheryl Chick
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858
Email: chickc@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.


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