Bioinformatics methods are increasingly applied in clinical research studies to approach research questions from novel perspectives. For example, natural language processing (NLP) enables use of information previously embedded in narrative clinical notes. Leveraging experience from the past decade in developing and applying bioinformatics tools for clinical studies, the VERITY Bioinformatics Resource Core supports investigators who seek to apply these tools to their research in rheumatic and musculoskeletal disease.

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Pediatric and adult rheumatic and musculoskeletal diseases challenge the clinical researcher:

• They affect the population across the lifespan,
• They impact a broad range of patient-centered outcomes,
• They are rarely cured, and
• They often have multiple possible treatment strategies.

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The VERITY Methodology Core addresses many complex methodologies that researchers encounter when studying rheumatic and musculoskeletal (MSK) disorders. These conditions persist for decades and have a profound impact on the patient’s quality of life. Epidemiologic studies to identify persons at high risk for these disorders and to identify factors leading to worse prognoses merit a high priority, and clinical trials to establish treatment efficacy are even more crucial. Both types of studies must account for the complexity of the phenotype and longevity of the clinical course. Furthermore, they must address the balance between efficacy and toxicity in treatments for rheumatic and MSK disorders.

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In May 2018, 15 trainees and junior faculty in adult and pediatric rheumatology from across the United States arrived at Brigham and Women’s Hospital in Boston for the inaugural VERITY/Brigham Course in Rheumatology Clinical Research. The course is aimed at early stage investigators in rheumatology and musculoskeletal diseases who are performing clinical, epidemiologic or patient-oriented research studies.

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Prior work in Lupus Nephritis has shown that immune cell infiltration, especially that of monocytes, is associated with pathologic tissue remodeling and declining renal function. A deeper understanding of infiltrating monocytes could yield more accurate interpretations of histopathologic lesions, better disease predictors, and new therapeutic concepts. Newer technologies offer a promising path toward this goal. Single cell-RNA sequencing (scRNA-seq) enables the molecular classification of cell states based on the expression of thousands of genes, and multiplex-immunofluorescent imaging enables precise spatial localization of these cell states in the context of diseased tissue. Groundwork to merge these technologies derives from our work with the Accelerating Medicines Partnership (AMP) consortium.
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Synovial fibroblasts are mesenchymal cells in the synovium that regulate tissue homeostasis in healthy joints. However, in rheumatoid arthritis (RA), synovial fibroblasts assume pathological functions as they recruit infiltrating immune cells that degrade cartilage and bone, leading to joint damage.  Therapies aimed at synovial fibroblasts in RA have the theoretical potential to prevent joint damage while sparing side-effects from immunosuppression. However, incomplete understanding of synovial fibroblast heterogeneity and the pathways that regulate their identity pose major challenges to the therapeutic targeting of these cells.  We sought to attack this problem by applying cutting-edge single cell technology to examine the biology of synovial fibroblasts in RA.
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It is estimated that at least 25 percent of all individuals with lupus are hospitalized each year. These hospitalizations tend to be associated with significant morbidity and mortality and are costly for the health care system. The U.S. Agency for Healthcare Research and Quality (AHRQ) developed a set of prevention quality indicators which they defined as conditions that “should be treatable on an outpatient basis, or that could be less severe if treated early and appropriately.” The AHRQ has used this set of “ambulatory care sensitive conditions” to identify populations at risk for hospitalization and to better understand the breakdown of health care services for these vulnerable groups. Examples of these conditions include diabetic complications, pulmonary disease (e.g. asthma) exacerbations, and pyelonephritis.
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