Description:
364 Methods and Software for Integration of Cancer Metabolomic Data with Other –Omic and Imaging Data
Fast-Track proposals will be accepted.
Direct-to-Phase II will not be accepted.
Number of anticipated awards: 2-3
Budget (total costs, per award): Phase I: $225,000 for 9 months; Phase II: $1,500,000 for 2 years
PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.
Summary
Metabolomics is the study of small molecules participating in cellular metabolism. Advances in metabolic profiling technologies have made it possible to simultaneously assay hundreds of metabolites, providing insight into an organism’s metabolic status. Several studies suggest that metabolomics may identify novel biomarkers for a diverse range of disease, including cancer. Furthermore, metabolites may play important regulatory roles in disease pathways and even serve as effectors of disease processes.
The metabolome is particularly responsive to both environmental and biological regulatory mechanisms, such as epigenetic and post-translational modification and transcription. Additionally, metabolites are the closest link to the phenotype and therefore offer a unique opportunity for phenotype characterization. However, metabolomics alone is unlikely sufficient to achieve this. Therefore, developing bioinformatic methods for integration of metabolite data with other -omic (proteomics, transcriptomics, genomics, epigenomics) and/or cancer imaging data would allow for
Page 91
significant advances in deciphering the biological relationships resulting in an observed phenotype. Importantly, this will also help leverage existing human data to combine metabolite and other –omics and/or cancer imaging data to detect subtler and more complex associations among variables, thereby promoting greater efficiency and return on investment. In turn, it will enhance opportunities to identify novel cancer biomarkers of risk, aggressiveness, therapeutic effectiveness, and prognosis, develop and/or enhance predictive models of cancer, and evaluate the tumor microenvironment. Ultimately, developing these bioinformatics methods will support precision medicine-focused clinical research.
Project Goals
The goal of this project is to develop new and innovative bioinformatic methods to integrate metabolite data with and other –omics and/or cancer imaging data and ultimately design scalable software tool(s) that apply these methods to automate the integration of the data. In Phase I, offerors should provide evidence that bioinformatic methods integrating identified metabolite data with other –omics and/or imaging data have been effectively developed, can be implemented across data inputs from at least one analytical technology used in metabolomics and at least one analytical technology used in genomics, proteomics, epigenomics, transcriptomics, or cancer imaging; and demonstrate readiness to proceed to Phase II. Additionally, phase I should be used to demonstrate the framework for scalable software tool(s) that apply the bioinformatic methods to automate the integration of metabolite and other –omics and/or cancer imaging data. In Phase II, offerors should expand the bioinformatic methods to include unidentified metabolite peaks, in addition to identified metabolite data, and demonstrate metabolite data integration other –omics and/or cancer imaging data.
To apply for this topic, offerors will need to demonstrate usability of scalable software through the following: 1) beta-test and finalize automated file transfer, data importation protocols, metabolite and genomic data integration applications and reporting tools developed in Phase I; 2) demonstrate that the software system adheres to established community data formats (e.g. standards of the Genomic Data Commons) and uses open application programming interfaces (APIs); 3) develop, beta-test, finalize and demonstrate the graphical user interface (GUI); and 4) demonstrate the software system’s ability to integrate data from planned Phase II technology compatibility matrix data sources using automated algorithms and bioinformatic methods.
Phase I Activities and Deliverables
• Establish a project team including proven expertise in metabolomics analytical technologies, genomics, proteomics, epigenomics, transcriptomics and/or cancer imaging analytical technologies (as appropriate), cancer biology, epidemiology, biostatistics/bioinformatics, statistical genetics (if genomic data is being integrated), computer technology, and software implementation (including requirements analyst, software engineer, user interface design, quality assurance, and technical documentation).
• Develop bioinformatic methods for identified metabolite data integration with other –omics and/or cancer imaging data for at least one analytical technology used in metabolomics (preferably liquid-chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and/or NMR) and at least one analytical technology used in in genomics, proteomics, epigenomics, transcriptomics, or cancer imaging. Datasets with cancer outcomes must be used.
• Develop data formats that support the import and export of individual datasets and “combined” datasets, store structured data from different sources of metabolite and other –omics and/or cancer imaging data, and are readily used for data integration and QC protocols.
• Finalize data formats and structure, data collection, transport and importation methods for targeted Phase I data inputs.
• Provide wireframes and user workflows for the proposed graphical user interface (GUI) and software functions that:
• Support the import and export of individual datasets and “combined” datasets;
• Implement, script or automate all features and functions of the data integration tool(s); and
• Conduct QC of “combined” datasets.
• Provide a report including a detailed description and/or technical documentation of the proposed:
• Specific approach to metabolite and other –omic and/or cancer imaging data integration;
Page 92
• Specific approach to QC;
• Data standards for transfer and importation of individual metabolite other –omic and/or cancer imaging data and storage of individual and “combined” metabolite and other –omic and/or cancer imaging data;
• Data visualization, feedback, and reporting systems for individual and “combined” metabolite and other –omic and/or cancer imaging data;
• Technology compatibility matrix for Phase I and Phase II metabolomics and other –omic and/or cancer imaging data sources, including identified metabolites (Phase I) / unidentified metabolite peaks (Phase II).
• Software tool(s);
• Transparent, documented, and non-proprietary bioinformatic methods; and
• Description of additional software and/or hardware required for use of the tool.
• Finalized data formats and structure, data collection, transport, and importation methods for targeted data inputs; and
• Includes funds in budget to present Phase I findings and demonstrate the wireframes and user workflows for the GUI and software functions to an NCI evaluation panel.
• Develop functional prototype software that integrates data from planned Phase I technology compatibility matrix data sources using automated algorithms and methods.
• Include funds in the Phase I budget to present project deliverable and the prototype software tools to an NCI panel for evaluation.
Phase II Activities and Deliverables
• Expand the bioinformatic methods to include unidentified metabolite peaks, in addition to identified metabolite data, and demonstrate metabolite data integration with other –omics and/or cancer imaging data, using at least one analytical technologies used in metabolomics (preferably liquid-chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and/or NMR) and at least one analytical technology used in in genomics, proteomics, epigenomics, transcriptomics, or cancer imaging. Datasets with cancer outcomes must be used.
• Demonstrate usability of scalable software through the following:
• Beta-test and finalize automated file transfer, data importation protocols, metabolite and genomic data integration applications and reporting tools developed in Phase I.
• Demonstrate that the software system adheres to established community data formats (e.g. standards of the Genomic Data Commons) and uses open APIs;
• Develop, beta-test, finalize and demonstrate the GUI.
• Demonstrate the software systems ability to integrate data from planned Phase II technology compatibility matrix data sources using automated algorithms and bioinformatic methods.
• Conducts usability testing of the GUI elements of the metabolomics and other –omic and/or cancer imaging data integration tool(s).
• Develop systems documentation where applicable to support the software and bioinformatic methods.
• In the first year of the contract, provide the program and contract officers with a letter(s) of commercial interest.
• In the second year of the contract, provide the program and contract officers with a letter(s) of commercial commitment.
