An evaluation of the National Institutes of Health grants portfolio: identifying opportunities and challenges for multi-omics research that leverage metabolomics data.

BACKGROUND: Through the systematic large-scale profiling of metabolites, metabolomics provides a tool for biomarker discovery and improving disease monitoring, diagnosis, prognosis, and treatment response, as well as for delineating disease mechanisms and etiology. As a downstream product of the genome and epigenome, transcriptome, and proteome activity, the metabolome can be considered as being the most proximal correlate to the phenotype. Integration of metabolomics data with other -omics data in multi-omics analyses has the potential to advance understanding of human disease development and treatment. AIM OF REVIEW: To understand the current funding and potential research opportunities for when metabolomics is used in human multi-omics studies, we cross-sectionally evaluated National Institutes of Health (NIH)-funded grants to examine the use of metabolomics data when collected with at least one other -omics data type. First, we aimed to determine what types of multi-omics studies included metabolomics data collection. Then, we looked at those multi-omics studies to examine how often grants employed an integrative analysis approach using metabolomics data. KEY SCIENTIFIC CONCEPTS OF REVIEW: We observed that the majority of NIH-funded multi-omics studies that include metabolomics data performed integration, but to a limited extent, with integration primarily incorporating only one other -omics data type. Some opportunities to improve data integration may include increasing confidence in metabolite identification, as well as addressing variability between -omics approach requirements and -omics data incompatibility.

Overview of Research on Germline Genetic Variation in Immune Genes and Cancer Outcomes.

Since the late 19th century, the immune system has been known to play a role in cancer risk, initiation, and progression. Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for autoimmune and inflammatory diseases, yet the connection between human genetic variation and immune-mediated response to cancer treatments remains less well-explored. Understanding inherited genetic variation, with respect to germline genetic polymorphisms that affect immune system pathways, could lead to greater insights about how these processes may best be harnessed to successfully treat cancer. Our goal in this manuscript was to understand progress and challenges in assessing the role of inherited genetic variation in response to cancer treatments. Overall, the 39 studies reviewed here suggest that germline genetic variation in immune system-related genes may potentially affect responses to cancer treatments. Although further research is needed, considering information on germline immune genetic variation may help, in some cases, to optimize cancer treatment.

GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans.

Inborn errors of immunity (IEIs) unveil regulatory pathways of human immunity. We describe a new IEI caused by mutations in the GTPase of the immune-associated protein 6 (GIMAP6) gene in patients with infections, lymphoproliferation, autoimmunity, and multiorgan vasculitis. Patients and Gimap6-/- mice show defects in autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)-containing lipids. We find that GIMAP6 complexes with GABARAPL2 and GIMAP7 to regulate GTPase activity. Also, GIMAP6 is induced by IFN-γ and plays a critical role in antibacterial immunity. Finally, we observed that Gimap6-/- mice died prematurely from microangiopathic glomerulosclerosis most likely due to GIMAP6 deficiency in kidney endothelial cells.