RESUMO
MOTIVATION: A variety of in silico tools have been developed and frequently used to aid high-throughput rapid variant classification, but their performances vary, and their ability to classify variants of uncertain significance were not systemically assessed previously due to lack of validation data. This has been changed recently by advances of functional assays, where functional impact of genetic changes can be measured in single-nucleotide resolution using saturation genome editing (SGE) assay. RESULTS: We demonstrated the neural network model AIVAR (Artificial Intelligent VARiant classifier) was highly comparable to human experts on multiple verified datasets. Although highly accurate on known variants, AIVAR together with CADD and PhyloP showed non-significant concordance with SGE function scores. Moreover, our results indicated that neural network model trained from functional assay data may not produce accurate prediction on known variants. AVAILABILITY AND IMPLEMENTATION: All source code of AIVAR is deposited and freely available at https://github.com/TopGene/AIvar. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Edição de Genes , Software , Simulação por Computador , Humanos , Redes Neurais de ComputaçãoRESUMO
Radiation therapy, one of the major treatment options for cancer, can cause delayed heart damage. The circular RNA (circRNA) circFOXO3 (hsa_circ_0006404) is associated with cancer progression. However, the functions of circFOXO3 in radiationinduced cardiotoxicity remains unknown. The present study aimed to identify the functions of cirFOXO3 in radiationinduced cardiotoxicity. The present study established circFOXO3knockdown (KD) or overexpressing (OE) cardiomyocytes. Functional assay results showed that KD of circFOXO3 in cardiomyocytes significantly increased DNA damage and apoptosis after radiation. By contrast, OE of circFOXO3 reduced DNA damage and apoptosis rates in response to radiation. Mechanistically, KD of circFOXO3 elevated the levels of Bax, caspase 3 and caspase 7, and decreased Bcl2 expression, whereas OE of circFOXO3 decreased Bax, caspase 3 and caspase 7 expression, and increased Bcl2 expression. Thus, the present study indicated that circFOXO3 protected cardiomyocytes from radiationinduced cardiotoxicity by reducing DNA damage and apoptosis. circFOXO3 may be a potential therapeutic target against radiationinduced cardiotoxicity.