Despite the increasing availability of genomic data and enhanced data analysis procedures, predicting the severity of associated diseases remains elusive in the absence of clinical descriptors. To address this challenge, we have focused on the K7.2 voltage-gated potassium channel gene (), known for its link to developmental delays and various epilepsies, including self-limited benign familial neonatal epilepsy and epileptic encephalopathy. Genome-wide tools often exhibit a tendency to overestimate deleterious mutations, frequently overlooking tolerated variants, and lack the capacity to discriminate variant severity. This study introduces a novel approach by evaluating multiple machine learning (ML) protocols and descriptors. The combination of genomic information with a novel Variant Frequency Index (VFI) builds a robust foundation for constructing reliable gene-specific ML models. The ensemble model, MLe-KCNQ2, formed through logistic regression, support vector machine, random forest and gradient boosting algorithms, achieves specificity and sensitivity values surpassing 0.95 (AUC-ROC > 0.98). The ensemble MLe-KCNQ2 model also categorizes pathogenic mutations as benign or severe, with an area under the receiver operating characteristic curve (AUC-ROC) above 0.67. This study not only presents a transferable methodology for accurately classifying missense variants, but also provides valuable insights for clinical counseling and aids in the determination of variant severity. The research context emphasizes the necessity of precise variant classification, especially for genes like , contributing to the broader understanding of gene-specific challenges in the field of genomic research. The MLe-KCNQ2 model stands as a promising tool for enhancing clinical decision making and prognosis in the realm of -related pathologies.
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http://dx.doi.org/10.3390/ijms25052910 | DOI Listing |
BMC Cardiovasc Disord
December 2024
Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China.
Background: Familial hypercholesterolemia (FH) is a genetically inherited disorder caused by monogenic mutations or polygenic deleterious variants. Patients with FH innate with significantly elevated risks for coronary heart disease (CHD). FH prevalence based on genetic testing in Chinese CHD patients is missing.
View Article and Find Full Text PDFGenet Med
December 2024
Genetics Department, Hospices Civils de Lyon, Lyon, France; Neuromyogene Institute, Pathology and Genetics of neuron and muscle, CNRS UMR 5261 INSERM U1315, University of Lyon - Université Claude Bernard Lyon 1, Lyon, France. Electronic address:
Cell Mol Biol (Noisy-le-grand)
November 2024
Department of Plant Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al-Khoud 123, Muscat, Oman.
Tomato yellow leaf curl virus-Oman (TYLCV-OM), a variant of the Tomato yellow leaf curl virus-Iran (TYLCV-IR) strain, was identified in 2005 as the cause of tomato yellow leaf curl disease (TYLCD) in Oman and is associated with a betasatellite namely as Tomato leaf curl betasatellite (ToLCB). Surveys were carried out from three diverse Governorates of Oman to investigate the correlation between the betasatellite and the virus. The visual assessment and scoring of infected tomato plants in the field revealed that the association of betasatellite with the disease was highest in Sharqia at 77%, followed by Dakhlia at41% and lowest in Batinah at30% .
View Article and Find Full Text PDFActa Neuropathol Commun
December 2024
Institute of Myology, Neuromuscular Morphology Unit, Sorbonne Université, INSERM, GHU Pitié-Salpêtrière, Paris, France.
Neuromuscular disorders (NMD) with neonatal or early infantile onset are usually severe and differ in symptoms, complications, and treatment options. The establishment of a diagnosis relies on the combination of clinical examination, morphological analyses of muscle biopsies, and genetic investigations. Here, we re-evaluated and classified a unique collection of 535 muscle biopsies from NMD infants aged 0-6 months examined over a period of 52 years.
View Article and Find Full Text PDFOrphanet J Rare Dis
December 2024
Thrombosis Research Center, Beijing Jishuitan Hospital, Capital Medical University, Xicheng District, Beijing, 100035, China.
Background: Identification of mutations in the SERPINC1 has illuminated the intricate pathways underlying antithrombin (AT) deficiency. Our group identified a variation in the SERPINC1 gene (c.964 A > T, p.
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