Amin Ravaei

Rheumatoid Arthritis (RA) is a complex autoimmune disorder with two distinct subsets known as seropositive RA and seronegative RA, where the presence or absence of serological biomarkers makes this difference. RA is a genetically predisposed disease mainly studied in the seropositive subset, leaving seronegative RA poorly explored, with an overlooked explanation for the role of known genetic predisposition in it. This study hypothesizes that the poor explanation is due to the genome-wide genotyping methodology, which predominantly focuses on common single nucleotide polymorphisms (SNP) and small indels. Therefore, this project aims to unravel the hidden genetic landscape of seronegative RA using cutting-edge long-read HiFi sequencing technology, which identifies structural variations within the genome. Additionally, the project aims to improve the researcher´s skills through different levels of training, including advanced bioinformatics, scientific knowledge, research methodology, and organizational skills, to pave the way for an independent researcher position. The project´s objectives will be achieved through six working packages addressing the study cohort, long-read sequencing, bioinformatics analysis, training and career development, dissemination and communication, and project management. The outcomes of the project will be disseminated through various plans targeting the scientific community, end-users, and the general public. The project will follow and support the open science policy during dissemination. In the short term, the results of this project will greatly enhance our scientific understanding of the genetic background of seronegative RA. In the medium term, the findings will contribute to improved diagnosis, effective personalized treatment strategies, and the development of targeted therapies. Over the long term, this research will aid in deciphering the pathogenesis of seronegative RA, thus assisting in prevention.