Bioinformatics Core Supports Investigators Who Seek to Use Big Data

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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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Methodology Core Finds the Optimal Study Design for Your Innovative Research Idea

figure 1. Methodolic approaches to clinical priority areas

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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VERITY Enrichment Core Offers Weeklong Brigham Course in Rheumatology Clinical Research

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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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Mapping Monocyte States in Class IV Human Lupus Nephritis

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Paul J. Hoover, MD, PhD

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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Elucidating the Biology and Role of Synovial Fibroblasts in Rheumatoid Arthritis

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Kevin S. Wei, MD, PhD

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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Development of a Set of Potentially Preventable Adverse Conditions Specific to Lupus: A Delphi Consensus Study

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Candace H. Feldman, MD, MPH, ScD

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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Abdominal Obesity and Risk of Developing Rheumatoid Arthritis in Women

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Bing Lu, MD, DrPH

Individuals with obesity, particularly abdominal obesity, are at an increased risk of hypertension, dyslipidemia, diabetes, coronary heart disease, stroke, cancer, and all-cause mortality. Several studies have observed an association between obesity and increased risk of rheumatoid arthritis (RA). Abdominal obesity is associated with visceral fat and has been a stronger predictor of obesity-related health risk, such as cardiovascular disease, than overall obesity as measured by BMI. We sought to investigate whether abdominal obesity per se predicts RA risk in two large prospective cohorts, the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII).
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Metabolic Pathways in Monocyte Development Identified Using HoxB8 Model Cells

Metabolism is a hot topic in immunology. Immune cells carry out diverse functions by exploiting different pathways of taking in nutrients and generating energy. Accordingly, metabolic processes such as glycolysis and oxidative phosphorylation are now front and center in understanding how cells behave in the context of normal and pathogenic immune responses. Read More

Using CyTOF Mass Cytometry and RNA-seq to Identify New Cell Populations in Arthritis

The inflamed joint is a complex place. Many different types of cells must interact with each other to initiate and sustain inflammation and tissue injury. These include both those resident in the joint before inflammation started and cells that were recruited or developed later. To get a handle on this complexity, investigators need methods that can provide highly detailed portraits of individual cells. A major goal of the Joint Biology Consortium’s Cellular Systems Core, directed by Dr. Jim Lederer, is to accelerate research by JBC members through two such methods: cytometry by time of flight (CyTOF) mass cytometry and RNA sequencing (RNA-seq). Read More