Homo sapiens Transcriptome or Gene expression

Tick bites and tick-related diseases are on the rise. Diagnostic tests that identify well-characterised tick-borne pathogens (TBPs) possess limited capacity to address the causation of symptoms associated with poorly characterised tick-related illnesses. Identification of local signals in tick-bitten skin that can be detected systemically in blood would have both clinical (diagnostic or prognostic) and research (mechanistic insight) utility, as a blood sample is more readily obtainable than tissue biopsies. We hypothesised that blood samples may reveal signals which reflect relevant local (tissue) events, and that the time course of these signals may align with local pathophysiology. As a first step towards testing this hypothesis, we contrasted molec-ular signatures in skin biopsies taken from the tick-bite location of human participants along with peripheral blood signatures obtained at the same time. This approach captures differentially ex-pressed molecules across multiple omics datasets derived from peripheral blood (including cel-lular and cell-free transcriptomics, proteomics, metabolomics, and DNA methylation), and skin biopsies (spatial transcriptomics). Our data revealed that extracellular matrix organisation and platelet degranulation pathways were upregulated in skin within 72 hours of a tick bite. The same signals appeared in blood, where they then remained elevated for three months, displaying lon-gitudinally consistent alterations of biological functions. Despite the limited sample size these data represent proof-of-concept that molecular events in the skin following a tick bite can be de-tectable systemically. This underscores the potential value of blood samples, akin to liquid biop-sy, to capture biomarkers reflecting local tissue processes.