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Developing preliminary blood metabolomics-based biomarkers of insufficient sleep in humans

ABSTRACT:

ORGANISM(S): Homo Sapiens

TISSUE(S): Blood

PROVIDER: ST001440 | MetabolomicsWorkbench |

REPOSITORIES: MetabolomicsWorkbench

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Project description:To better understand the relationship between peripheral blood- and brain-based epigenetic activity, we conducted a pilot study on captive baboons (Papio hamadryas) to investigate correlations between miRNA expression in peripheral blood mononuclear cells (PBMCs) and 14 different cortical and subcortical brain regions, represented by two study groups comprised of 4 and 6 animals. Using next-generation sequencing, we identified 362 miRNAs expressed at ≥10 read counts in 80% or more of the brain samples analyzed. Nominally significant pairwise correlations (one-sided P<0.05) between peripheral blood and mean brain expression levels of individual miRNAs were observed for 39 and 44 miRNAs in each group. When miRNA expression levels were averaged across animals within the groups, pairwise correlations between PBMCs and individual brain regions are all highly significant (P<2.2x10^-16), although correlations between brain regions are markedly stronger (rs=0.86-0.99) than those between blood and brain (rs=0.47-0.57). Principal component analysis revealed differentiation in miRNA expression between peripheral blood and the brain regions for the first component (accounting for ~75% of variance). Linear mixed effects modeling attributed most of the variance in expression to differences between miRNAs (>70%), with non-significant 7.5% and 13.1% assigned to differences between blood and brain-based samples in the two study groups. Hierarchical UPGMA clustering revealed two major co-expression branches that are evident in both groups, with one comprised of miRNAs hyper-expressed in blood relative to the brain samples, exhibiting an enrichment of miRNAs expressed in immune cells (CD14+, CD15+, CD19+, CD3+, and CD56+ leukocytes) among the top blood-brain correlates. In the other major branch, hypo-expression in the blood samples was observed, with enrichment for miRNAs associated with Alzheimer’s Disease among its top correlates. Although some differentiation was observed between tissue types, these preliminary findings reveal wider correlated patterns between blood- and brain-expressed miRNAs, suggesting the utility of blood-based miRNA profiling for investigating by proxy the epigenetic underpinnings of neurological and neuroinflammatory processes in the brain.

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Developing preliminary blood metabolomics-based biomarkers of insufficient sleep in humans

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