ABSTRACT- DIAGNOSTIC CORE The Diagnostics Core provides comprehensive laboratory testing for Lyme disease in a CLIA-certified clinical laboratory setting. Its purpose is to provide standardized laboratory services to the Clinical Core, to assist in characterizing enrolled subjects, and to provide archived human samples to support the Projects. Laboratory testing will include only well-established assays and procedures, rather than experimental diagnostic methods that will be evaluated in the Projects. Services provided by the Diagnostics Core will include pre-analytical sample processing (e.g., serum or plasma separation, isolation of peripheral blood mononuclear cells); routine chemistry and hematology tests; serum antibody testing using a standardized suite of well-described commercial assays selected for high performance and reproducibility; skin biopsy culture and PCR for Borrelia performed using established protocols; and multiplexed PCR targeting a full complement of tick-borne infectious agents. The Diagnostics Core will also manage plasma sample transport to a referral laboratory for pathogen detection using metagenomic sequencing.