- What type of metabolites will be analyzed by the Metabolomics Core?
- How will the UDN assign patients to the Metabolomics Core?
- FOA instructions request a description of how the Core would go about working up a patient's samples. Will a dataset be provided to use as an example or should we describe a general approach and provide examples from past experience?
- If we are experienced with incorporating other types of analyses in addition to metabolomics in evaluating patients or in gene function studies, should we describe our broader approach to difficult patient diagnoses?
- Should a specific aim be expanded on methods and technology to improve the application of metabolomics as a diagnostic tool?
- For patient sample workup, will the Metabolomics Core have access to clinical and phenotypic information and the full sequencing data from the respective patients?
The UDN Metabolomics Core will be analyzing biological samples from patients with rare and difficult to diagnose diseases. Therefore the samples will be analyzed for a broad range of both typical and atypical metabolites. Before sample analysis, patients will have had a first phase work up that may well include commonly available laboratory tests (e.g., amino acids, organic acids, enzymes, vitamins, hormones, etc.) and may receive whole genome or whole exome sequencing. After this initial phase of testing, the patients’ results will be carefully reviewed and with the advice of the Metabolomics Core, a systematic plan for phase 2 testing will be developed that may include metabolomics analysis.
Some staff from the Metabolomics Core will be members of the UDN Steering Committee and participate in review of initial data obtained from UDN patients. The decision on which patients should receive metabolomics testing will be made collectively and a Work Group may be created to review these decisions.
3. FOA instructions request a description of how the Core would go about working up a patient’s samples. Will a dataset be provided to use as an example or should we describe a general approach and provide examples from past experience?
Describe your general process for working up biological samples from undiagnosed clinical cases. Please include any experiences you have had in processing non-standard, atypical metabolites from clinical specimens and describe any that resulted in establishing diagnoses in difficult cases.
4. If we are experienced with incorporating other types of analyses in addition to metabolomics in evaluating patients or in gene function studies, should we describe our broader approach to difficult patient diagnoses?
Yes. The Metabolomics Core will be part of a large team made up of members from the Coordinating Center, Clinical Sites, Sequencing Cores and Model Organism Center. This team will work together to formulate a broad approach to successfully diagnose UDN patients. Describing previous experiences with multi-functional teams to develop comprehensive approaches would be a benefit.
No. The specific aims of this FOA should emphasize how metabolomics will be applied to aid in the diagnoses of UDN patients. The research will be through the identification of metabolites critical in understanding the link between gene variants, metabolites and phenotype. The Metabolomics Core will not provide routine metabolite profiling services but work as a member of the UDN Steering Committee to plan follow up testing that may include unknown metabolite identification and measurement of the levels of these unusual metabolites.
Yes, the UDN anticipates considerable communication and collaboration between the Metabolomics Core and the Model Organisms Screening Center, the Clinical Sites and Sequencing Cores in evaluating the patient and the putative pathogenicity of any candidate gene variants. Clinical and sequencing data will be shared to the fullest extent possible.