Periodic Reporting for period 2 - DIAMONDS (Diagnosis and Management of Febrile Illness using RNA Personalised Molecular Signature Diagnosis)
Berichtszeitraum: 2021-07-01 bis 2022-12-31
The current approach to infectious and inflammatory diseases is to first exclude the possibility of severe bacterial infection through conventional microbiological investigation including blood cultures and cultures from other sites. As results of cultures may not be available for 24-48 hours, patients suspected of having significant infections are first treated with broad-spectrum antibiotics while awaiting the culture results. Current diagnostic approaches fail to identify the cause in a high proportion of cases and many patients undergo extensive investigation and treatment with broad-spectrum antibiotics because the possibility of infection cannot be excluded. A small proportion of patients with fever and inflammation do not have infections but have serious and persistent inflammatory disorders that require specific treatments. These are often only diagnosed after a lengthy process of first excluding infection and then stepwise exclusion of other conditions.
DIAMONDS aims to revolutionise the diagnostic process for infectious and inflammatory diseases by demonstrating and bringing into clinical use diagnostic approaches based on host molecular signatures. The underlying hypothesis in DIAMONDS is that individual infectious and inflammatory conditions are associated with unique patterns of genes that are activated or repressed in the patient’s blood in response to the individual disease. These unique molecular patterns can be identified through genome-wide RNA sequencing (RNA-Seq) and can be used as a “molecular signature” or “fingerprint” specific for each disease process. DIAMONDS builds on our previous EU-funded EUCLIDS and PERFORM studies which have recruited over 10,000 patients with fever and inflammation at multiple hospitals in Europe, Africa, and Asia. We have established proof of principle that individual diseases, such as tuberculosis, bacterial infections, viral infections, or inflammatory diseases like Kawasaki disease and rheumatoid arthritis, are characterised by unique RNA signatures. DIAMONDS will move the concept of diagnosis of infection and inflammatory disease by RNA molecular signatures a step closer to clinical introduction by first expanding the range of infectious and inflammatory diseases for which we have gene expression data, to cover a wide range of infectious and inflammatory diseases. Using samples from carefully phenotyped patients, DIAMONDS will undertake RNA-Seq and bioinformatic analyses to identify the RNA profile of common infectious and inflammatory diseases. DIAMONDS will establish a European RNA transcriptomic library which will be available to researchers and clinicians worldwide as a resource for understanding infectious and inflammatory diseases.
Using bioinformatic methods we will select the smallest number of genes that enable individual infectious and inflammatory diseases to be distinguished from each other. We will develop a diagnostic device to rapidly detect the genes required to distinguish common diseases, and test the device to measure personalised molecular signatures in a prospective cohort. By the end of the study, we aim to have validated the concept of diagnosis of infectious and inflammatory diseases using personalised molecular signatures, established the accuracy of a diagnostic device to detect personalised molecular signatures, and provided evidence on cost-effectiveness and clinical value of a new diagnostic approach through RNA molecular signature diagnosis.