Background
Last updated: 2023-08-16
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Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severely disabling, chronic illness that affects approximately 1-3 million Americans. ME/CFS can be briefly described as presenting with severe unrelenting fatigue,widespread unexplained pain, general malaise or feelings of illness described as flu-like,post-exertional malaise syndrome which is characterized by the drastic reduction in physical and mental ability following exertion of any kind, GI and digestive problems,mental fogginess, and cardio-pulmonary abnormalities. The cause of ME/CFS is not well understood. The majority of ME/CFS patients can recall a time of either sudden onset of dysfunction from an illness or a gradual decline in function, and this most often occurs in adulthood. Many biological abnormalities have been identified in ME/CFS patients, such as altered cytokine responses indicating increased systemic inflammation, altered metabolic profiling, dysregulation of the immune system, and neuroinflammation. Despite a delay in initiation of genetic studies, there is now a growing body of knowledge indicating an underlying genetic predisposition. Studies have shown that having a family member with ME/CFS is one of the strongest predictive factors for the presence of disease; first-degree relatives of affected individuals were found to be three times more likely to develop ME/CFS than controls. We hypothesized that ME/CFS is a genetically inherited disease that results in disrupted metabolic regulation of the immune system,thus resulting in an inappropriately activated immune system.
Methods
We performed WGS on 23 ME/CFS patients with 10 first degree relative healthy controls. We utilized our custom WGS analysis software, Codicem, for interpretation of the data. Our methods, which have been used to uncover the genetic causes of disease in thousands of patients, support identification of all categories of molecular variation including genic and regulatory, protein-coding and non-protein coding, small variants and larger structural variants (SVs, including more complex types of rearrangements), chromosomal abnormalities, repeat expansions, mobile element insertions, and variants in regulatory regions that alter expression. In addition, we have used a variety of existing tools to perform network analyses of candidate loci identified inME/CFS patients. We have extracted pharmacogenomics data from these patients which can be applied towards better choices in prescribed drugs. We have also collected RNA samples on 10 ME/CFS patients for expression analysis and immune repertoire sequencing.
Performing WGS Analysis
Performing Bulk RNASeq Analysis
We have collected RNA samples on 29 ME/CFS patients for expression analysis and performed bulk RNA sequencing via Vantage.
Our lab uses nf-core’s rnaseq pipeline for secondary analysis which we’ve modified to work on the cluster, Cheaha, that we use.
