The BrAID study protocol: integration of machine learning and transcriptomics for brugada syndrome recognition

Morales, Maria‐Aurora; Piacenti, Marcello; Nesti, Martina; Solarino, Gianluca; Pieragnoli, Paolo; Zucchelli, Giulio; Ry, Silvia Del; Cabiati, Manuela; Vozzi, Federico

doi:10.1186/s12872-021-02280-3

Cited by 3 publications

(1 citation statement)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More such findings can help develop a comprehensive transcriptomic network of how coding and ncRNAs interact to coordinately influence the genotype and phenotype of BrS [82]. The prospective BrAID multicenter clinical study involving the integration of machine learning algorithms and transcriptomics is expected to shed new light on mechanisms of type 1 BrS [190]. Future studies need to also focus on the early detection of noncoding variants and ncRNAs in the prevention of life-threatening arrhythmias and SCDs in BrS.…”

Section: Discussionmentioning

confidence: 99%

Noncoding RNAs and Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Cardiac Arrhythmic Brugada Syndrome

Theisen,

Holtz,

Rajagopalan

2023

Cells

View full text Add to dashboard Cite

Hundreds of thousands of people die each year as a result of sudden cardiac death, and many are due to heart rhythm disorders. One of the major causes of these arrhythmic events is Brugada syndrome, a cardiac channelopathy that results in abnormal cardiac conduction, severe life-threatening arrhythmias, and, on many occasions, death. This disorder has been associated with mutations and dysfunction of about two dozen genes; however, the majority of the patients do not have a definite cause for the diagnosis of Brugada Syndrome. The protein-coding genes represent only a very small fraction of the mammalian genome, and the majority of the noncoding regions of the genome are actively transcribed. Studies have shown that most of the loci associated with electrophysiological traits are located in noncoding regulatory regions and are expected to affect gene expression dosage and cardiac ion channel function. Noncoding RNAs serve an expanding number of regulatory and other functional roles within the cells, including but not limited to transcriptional, post-transcriptional, and epigenetic regulation. The major noncoding RNAs found in Brugada Syndrome include microRNAs; however, others such as long noncoding RNAs are also identified. They contribute to pathogenesis by interacting with ion channels and/or are detectable as clinical biomarkers. Stem cells have received significant attention in the recent past, and can be differentiated into many different cell types including those in the heart. In addition to contractile and relaxational properties, BrS-relevant electrophysiological phenotypes are also demonstrated in cardiomyocytes differentiated from stem cells induced from adult human cells. In this review, we discuss the current understanding of noncoding regions of the genome and their RNA biology in Brugada Syndrome. We also delve into the role of stem cells, especially human induced pluripotent stem cell-derived cardiac differentiated cells, in the investigation of Brugada syndrome in preclinical and clinical studies.

show abstract

Section: Discussionmentioning

confidence: 99%