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Millions of new mutations have been discovered largely due to advancements in genome projects, but characterizing their effects through traditional wet-lab experiments remains labor-intensive and time-consuming. Functional prediction algorithms offer a solution by enabling the efficient screening of mutations, thereby saving time and resources. The objective of this study was to develop a competitive algorithm for predicting the functional impact of missense mutations. A unified database and substitution matrices containing predictor variables specifically for missense mutations were initially constructed. Subsequently, values for the predictor variables were collected from the training and test sets derived from the ClinVar and HumsaVar databases. A series of supervised machine learning classifiers were then trained, and their performance was evaluated using the test set. The best-performing model was additionally compared against ten currently available functional prediction algorithms. The proposed algorithm, XGBMut, demonstrates exceptional accuracy in classifying missense mutations while also exhibiting a competitive performance. Additionally, a user-friendly graphical interface was developed to enhance accessibility for professionals in various fields. Unlike most existing methods, XGBMut eliminates the need for a web server dependency and the installation of third-party software, making it a more versatile tool for users.
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http://dx.doi.org/10.1021/acsomega.4c10179 | DOI Listing |
Front Med (Lausanne)
August 2025
Research Centre for Medical Genetics, Moscow, Russia.
Acroscyphodysplasia (ASD) is an ultra-rare skeletal dysplasia characterized by severe brachydactyly, metaphyseal scaphoid knee deformities, growth retardation, and intellectual disability. To date, only seven cases of ASD have been reported, all associated with missense variants in the gene. We report a 7-year-old girl with ASD features, including midface hypoplasia, severe growth retardation (-4.
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September 2025
Center of Bioinformatics, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:
Parkinson's disease is a prevalent neurodegenerative disease, in which genetic mutations in many genes play an important role in its pathogenesis. Among these, a mutation in the PINK1 gene, a mitochondrial-targeted serine/threonine putative kinase 1 that protects cells from stress-induced mitochondrial dysfunction, is implicated in autosomal recessive Parkinsonism. However, the exact etiology is not well understood.
View Article and Find Full Text PDFLab Invest
September 2025
Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA. Electronic address:
Sinonasal mucosal melanoma (SNMM) is a rare aggressive malignancy of the sinonasal tract. Due to its advanced clinical presentation and frequent late-stage diagnosis, the 5-year survival rate is less than 30%, with an even worse prognosis in patients with distant metastasis (SNMM-M). Therefore, characterizing the molecular landscape of SNMM may provide novel therapeutic targets for SNMM-M.
View Article and Find Full Text PDFBrain Dev
September 2025
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Japan.
Hypomyelinating leukodystrophies (HLDs) are a group of inherited disorders characterized by impaired myelin formation in the central nervous system. Among them, Pelizaeus-Merzbacher disease (PMD) is a well-defined X-linked leukodystrophy caused by mutations in the PLP1 gene, including duplications, missense variants, and null mutations. Recent studies have revealed that different types of PLP1 mutations lead to distinct pathomechanisms: while missense mutations induce endoplasmic reticulum stress and activate the unfolded protein response (UPR), PLP1 duplications cause aberrant intracellular trafficking and cholesterol accumulation without UPR activation.
View Article and Find Full Text PDFMol Genet Genomics
September 2025
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012, Bern, Switzerland.
The aim of this study was to investigate three unrelated Simmental calves with atypical white coat color, identify potential genetic causes using a trio-based whole-genome sequencing approach, and assess the prevalence of the identified variants in the breed. Several inherited alleles affecting coat color, ranging from fawn to red spotted and white-headed, have been described in Simmental cattle originating from Switzerland. However, no genetic variant has yet been associated with an almost completely white coat in this breed.
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