NIH – The Human Biomolecular Atlas Program (HuBMAP): Rapid Implementation of Technologies that Will Accelerate Development of a Framework for Mapping the Human Body at High Resolution (UH3 Clinical Trial Not Allowed)

January 10, 2019 by kjt5j@virginia.edu

The Human BioMolecular Atlas Program (HuBMAP)

The vision for the Human BioMolecular Atlas Program (HuBMAP) is to catalyze development of a framework for mapping of the human body at high resolution to transform our understanding of tissue organization and function. This will be achieved by:

  • Accelerating the development of the next generation of tools and techniques for constructing high resolution spatial tissue maps that quantify multiple types of biomolecules either sequentially or simultaneously;
  • Generating foundational 3D tissue maps using validated high-content, high-throughput imaging and omics assays;
  • Establishing an open data platform that will develop novel approaches to integrating, visualizing and modelling imaging and omics data to build multi-dimensional maps, and making data rapidly findable, accessible, interoperable, and reusable by the global research community;
  • Coordinating and collaborating with other funding agencies, programs, and the biomedical research community to build the framework and tools for mapping the human body;
  • Supporting pilot projects that demonstrate the value of the resources developed by the program to study individual variation and tissue changes across the lifespan and the health-disease continuum.

This program is funded through the NIH Common Fund as a short-term, goal-driven strategic investment, with deliverables intended to catalyze research across multiple biomedical research disciplines.The NIH Common Fund supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

The HuBMAP Consortium will scale-up the range of tissues, technologies, data management and its community engagement activities throughout the duration of the program.

The five research initiatives that compose the program are:

  • Transformative Technology Development-This set of initiatives, the first of which was issued in FY2018, seek to establish proof-of-principle with initial validation of transformative new tools, techniques and methods for mapping the human body at high resolution.
  • Rapid Technology Integration– This set of initiatives, which starts in FY2019, will focus on enhancing, large-scale validation, and integration of emerging new technologies into the HuBMAP Consortium. The goal is to improve the quality and throughput of atlas generation at key steps of the production pipeline including sample collection, tissue mapping, and data integration and analysis.
  • Tissue Mapping Centers– These Centers, initially funded in FY2018, will build, benchmark, standardize, validate and generate extensive data from high-content, high-throughput imaging and omics technologies to produce 3D human tissue maps at high resolution. Centers will be expected to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation through to data integration, analysis and interpretation.
  • The HIVE – This multi-component collaboratory, funded in FY2018, will have responsibility for: 1) managing the data generated by the Consortium, 2) coordinating internal and external Consortium activities, 3) developing novel tools for visualizing, searching and modelling data and 4) building an atlas of tissue maps.
  • Demonstration Projects– The goal of this initiative, which is expected to start half way through the program pending the availability of funds, is to demonstrate how HuBMAP resources, in combination with new or other datasets or biospecimens as needed, can be used to build better statistical and analytic tools and models of cellular organization and communication in tissues.

Background

Understanding how tissue organization influences a cell’s molecular state, interactions, and history is critical for enhancing our understanding of variation in organ function across the lifespan and health-disease continuum. Despite vastly improved imaging and omics technologies and many important foundational discoveries, our understanding of how tissues are organized is restricted to a very limited number of microscopic structures. Better insights into the principles governing organization-function relationship will potentially lead to better understanding of the significance of inter-individual variability, changes across the lifespan, tissue engineering, and the emergence of disease at the biomolecular level. However, integrating imaging and omics analysis to comprehensively profile biomolecular distribution and morphology of tissues in a high throughput manner and placing this information into 3D tissue maps amenable to modelling and molecular perturbation has yet to be fully realized.

In a June 2016 meeting organized by the NIH, experts from the research community identified the following scientific priorities necessary to develop these tissue maps : 1) sourcing high quality tissue from multiple non-diseased human organ sites, 2) processing and preserving tissue for multiple imaging and omics assays, 3) quality control, validation and variation in data generation, 4) data coordination across multiple acquisition techniques, 5) annotation, curation and archiving of the data, 6) browsing, visualizing and searching the data, 7) building statistical and analytic techniques and models for nonlinear analysis of highly multidimensional data and 8) community engagement.

Objectives and Scope of Rapid Technology Implementation (RTI) Projects

The vision for the RTI projects is that they will nimbly integrate new technologies into the HuBMAP so that the Consortium can proactively adapt to the changing landscape and accelerate realization of its goals. This vision will be achieved by supporting projects that work in close collaboration with the existing HuBMAP Consortium to rapidly implement these technologies and optimize for their use.

All technologies are expected to significantly enhance understanding of the spatial distribution of a large number of biomolecules in the intra-, inter- and extra-cellular spaces of non-diseased human tissues. Because HuBMAP supports the analysis of a variety of organs and tissues, it is highly desirable that proposed technologies are adaptable to multiple tissue or data types, expand the expertise and capabilities of the Consortium, and can be readily integrated with existing and emerging projects. Technologies are not required to be completely novel and may include the integration or improvement of commercial off-the-shelf or open source products or code, but they are expected to add significant value and be successfully implemented within three years. Projects are also expected: (1) to have high impact by significantly extending existing capabilities of the Consortium, (2) to use a milestone-driven engineering approach that considers iterative design, testing and evaluation, and (3) to complement and integrate with existing technologies and pipelines used by the HuBMAP Consortium.

Successful projects are expected to: 1) define a realistic strategy and requirements for implementing the technology, 2) quickly optimize, benchmark and validate the technology in the context of the HuBMAP Consortium, 3) plan for training, testing, iteration, and contingencies and 4) realize sustained use of the technology by the Consortium. The ultimate goal is to have the technology ready for incorporation into one of the Tissue Mapping Centers or the HIVE Collaboratory. Pending availability of funds, there might be support for long-term integration through separate initiatives.

Proposed technologies should already have established proof-of-principle for technical feasibility using mammalian tissue and be validated in a lab setting. Typically, this stage of development is characterized by published results in a peer-reviewed journal, adoption of the technology by a third party, or availability of a beta prototype, as well as benchmarking indicative of superior performance. Applicants with technologies that do not have published results demonstrating feasibility using mammalian tissues are encouraged to wait for future HuBMAP Transformative Technology Development (TTD) FOAs (for more information of the distinctions between TTD and RTI projects please see https://commonfund.nih.gov/hubmap/generalfaqs).

Coordination and Collaboration

Successful applicants to this FOA will become members of the larger HuBMAP Consortium composed of investigators who have been funded in response to previous HuBMAP FOAs. The purpose of the Consortium is to enable groups to effectively collaborate with each other to maximize the chances of overall success of the program. In addition to completing the goals outlined in their applications, successful applicants will be expected to work collaboratively with all members of the Consortium to contribute to developing SOPs, data and metadata standards, metrics for data generation, participate in cross-site studies, engage in cross-training, and guide development of data analysis and visualization tools that can be used by the broader scientific community. A Steering Committee (SC) composed of all the funded principal investigators and NIH staff will develop and implement Consortium policies and guide overall direction of the Consortium to meet the goals of the program. This Steering Committee will meet regularly and be complemented by an Executive Committee and a set of working groups. NIH staff will also recruit outside experts (non-awardees) as External Program Consultants (EPCs) to provide advice directly to NIH. All HuBMAP investigators are required to attend the annual HuBMAP investigator meetings, regular teleconferences with Consortium members and NIH Staff for the duration of the funding cycle.

As well as being implemented in HuBMAP, NIH intends that the products of the RTI projects to be broadly available to establish the foundations for a human body map that other programs and the community could build upon; this includes methods, tools, reagents, biospecimens, datasets, and software. Projects will be expected to abide by Consortium policies for rapidly sharing their products within the Consortium and with the external research community.The robustness and reproducibility of experimental results are critical to the success of HuBMAP.In some cases, conducting additional critical experiments will be important for assessing progress. Therefore, NIH Program staff, in consultation with the PD/PI, may modify or add experiments to be conducted during the duration of an award.

Technology Focus

The scope of this FOA encompasses a wide range of technologies that may benefit the HuBMAP Consortium spanning the fields of tissue collection and preservation; high resolution, high content, high-throughput imaging; high sensitivity and high specificity transcriptomics, genomics and proteomics; extracellular environment and matrix composition; analysis, visualization and modelling of multidimension biomolecular data. Potential applicants are strongly advised to consult with the Scientific/Research Contact listed below to discuss the HuBMAP program and priorities, and whether proposed technologies will complement and enhance existing capabilities and address well-defined needs.

Technologies of particular interest include, but are not limited to:

  • Tools for reliable multi-site tracking of clinical biospecimens, including the use of unique identifiers, standard data dictionaries for associated metadata, and on-line querying and requests
  • High-sensitivity, high-resolution imaging techniques that can rapidly provide spectral data over large areas of tissue
  • Quantitative imaging analysis tools, including automated 3D image segmentation, feature extraction, and image annotation
  • Large, well-curated, well-annotated datasets of human anatomy and associated tools to assist with building a robust common coordinate framework system of the human body
  • Tools for rapid, high-resolution, in situ sequencing and analysis of a wide panel of nucleic acids derived from multiple tissues
  • Technologies for quantitative, comprehensive assessment of the extracellular environment of multiple human tissues, including characterization of structural proteins, enzymes, glycoproteins, polysaccharides and biomineralization
  • Sensitive and high-specificity assays for identification of different functional states of biomolecules, including post-transcriptional modification, post-translational modification, and proteoforms
  • Multi-scale data collection and integration methods from the molecular level to cellular and tissue levels.
  • Data visualization methods for intuitive atlas comparison and analysis.

Applications addressing the following topics will be deemed non-responsive and will not be reviewed:

  • Projects primarily focused on the pursuit of a biochemical mechanism that does not result in a technology that will significantly improve the Consortium’s capabilities to spatially map human tissues;
  • Projects proposing technologies that significantly overlap with those currently used by the Consortium or that are not compatible with existing assays or analysis techniques used by the Consortium;
  • Projects proposing technologies primarily for studying bio-fluids or dissociated cells;
  • Projects without published results reliably demonstrating proof-of-principle for the proposed technology using mammalian tissue;
  • Projects that do not propose a detailed implementation plan as described below.

Rapid Technology Implementation Project Structure

This FOA invites applications that will optimize, evaluate, and refine technologies that will significantly improve the data generation or analysis capabilities of the HuBMAP Consortium. This FOA uses the UH3 cooperative agreement mechanism to support the rapid implementation of technologies into the HuBMAP Consortium within three years. During this time, projects are expected to benchmark and optimize their technologies in the context of the Consortium and implement it into routine use.

Plug and play of new technologies into an existing consortium is a complex process and requires deep understanding of current processes and willingness of the consortia to change. Successful implementation of a new technology into an existing consortium needs a systematic plan with a shared vision of how the technology will accelerate the consortium reaching its goals. An implementation plan should clearly articulate the evidence that the technology is ready for use by the consortium, how it will accelerate the consortium’s goals, why it will be successfully adopted and what will drive sustained use of the technology. A successful plan will have well-laid out responsibilities, clear go/no-go decision points, flexible scheduling, iterative optimization, training, and stakeholder engagement. Careful attention to be paid to project management along-side technology issues.

A successful technology is one that will let consortium members achieve better results, more quickly or at lower cost. Usability is key because the barrier to adoption of the technology must be low, proficiency must lead to clear efficiencies in data generation or analysis and a pleasant user experience is needed for long-term use. Further, a flexible management plan is critical for guiding and evaluating adoption of a new technology in an existing setting. The implementation science and human factors communities have explored many of the variables that lead to successful adoption or failure of new technologies. Applicants are strongly encouraged to use a coordinated technical, social and organizational approach as part of their implementation plan and to propose quantitative methods to drive the design, implementation and evaluation of the proposed technology.

Because of the short-term nature of these projects, applications should focus on how they can successfully implement their technologies and define clear biannual milestones that are specific, measurable, achievable, realistic and time-bound. Milestones should include details of how success will be measured, go/no-go decision-making points for the project and alternative approaches. Prior to funding an application, NIH program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the review panel or NIH program staff. A final set of milestones will be specified each year in the Notice of Award. Progress towards achievement of the annual milestones and the overall goals will be regularly evaluated by NIH program staff and they may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, program synergy and priorities, competitive landscape, and availability of funds.

Technical Assistance Webinar

Potential applicants are strongly encouraged to contact NIH Staff to discuss the alignment of their proposed work with the goals of this FOA and the HuBMAP Consortium. A technical assistance webinar will be held for potential applicants on January 30, 2019 at 1 pm Eastern time. NIH staff and currently funded investigators will present an overview of the program and will be available to answer questions related to this FOA. Dial-in information for the call as well as a process for matchmaking potential applications with existing awardees will be announced on the HuBMAP website(https://commonfund.nih.gov/HuBMAP).A list of frequently asked questions (FAQs) related to the program is also posted on the website (https://commonfund.nih.gov/HuBMAP/generalfaqs).This information session is open to all prospective applicants, but participation is not a prerequisite to apply.

Deadline:  March 14, 2019 (letters of intent due 30 days prior to the deadline)

URL:  https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-19-002.html

Filed Under: Funding Opportunities