10084354LOCOME - Long Covid and ME/CFS Diagnosis and StratificationClosedCollaborative R&DInnovate UKThe LOCOME project will analyze integrated, multi-modal patient datasets to identify and stratify the disease mechanisms underpinning ME/CFS and long COVID. LOCOME will use these novel disease insights to develop diagnostic/prognostic tools that diagnose chronic fatigue patients more accurately and rapidly, and find the most appropriate treatments for specific patients based on their stratification, including existing medicines that can potentially be repurposed. Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and long COVID are debilitating conditions profoundly affecting the quality of life and socioeconomic participation of over 2 million (often younger, predominantly female) UK patients. They place a huge burden on the NHS in long-term treatment of patients and its own staff losses. They have a wide range of symptoms including deep fatigue, reduced muscle strength and cardiovascular effects such as palpitations, stroke/heart attack and microcoagulation risks. Currently there are no effective diagnostic tools or disease modifying therapies for ME/CFS or long COVID. Patients struggle for years to get a definitive diagnosis and then only receive symptomatic relief, including pain relief, anti-depressants, and cognitive behavioural therapy. PrecisionLife identified the first reproducible genetic associations with ME/CFS using its unique combinatorial analytics approach. Some of these genes were also found in a similar long COVID study. The LOCOME project will extend these analyses to include deeper multi-modal patient data for a wider group of patients from the DecodeME study, developed by Action for ME and gathered and analyzed via the University of Edinburgh, as well as additional long COVID patients. These data will be analyzed by PrecisionLife to identify disease risk and protective signatures for each disease, and the overlap between them. These disease signatures will be used to develop new diagnostic tools and combinatorial risk scores (CRS), which can rapidly triage patients presenting with potential ME/CFS or long COVID symptoms. In clinical use the LOCOME CRS could ultimately be derived from a low-density SNP genotyping array or low-pass whole genome sequencing. A GP suspecting ME/CFS or long COVID would simply take a patient's blood or saliva sample and send it to a standard genomic sequencing facility. Such tests are affordable, typically costing less than £100/patient. A LOCOME clinical decision support (CDS) tool will synthesize all of the patient's risk factors to provide a personalized recommendation for their diagnosis and/or treatment selection. This would rapidly flag any patients with strong risk factors for ME/CFS or long COVID and recommend referral to a specialist.