EPGAT: Gene Essentiality Prediction With Graph Attention Networks.

Identifying essential genes and proteins is a critical step towards a better understanding of human biology and pathology. Computational approaches helped to mitigate experimental constraints by exploring machine learning (ML) methods and the correlation of essentiality with biological information, especially protein-protein interaction (PPI) networks, to predict essential genes. Nonetheless, their performance is still limited, as network-based centralities are not exclusive proxies of essentiality, and traditional ML methods are unable to learn from non-euclidean domains such as graphs. Given these limitations, we proposed EPGAT, an approach for Essentiality Prediction based on Graph Attention Networks (GATs), which are attention-based Graph Neural Networks (GNNs), operating on graph-structured data. Our model directly learns gene essentiality patterns from PPI networks, integrating additional evidence from multiomics data encoded as node attributes. We benchmarked EPGAT for four organisms, including humans, accurately predicting gene essentiality with ROC AUC score ranging from 0.78 to 0.97. Our model significantly outperformed network-based and shallow ML-based methods and achieved a very competitive performance against the state-of-the-art node2vec embedding method. Notably, EPGAT was the most robust approach in scenarios with limited and imbalanced training data. Thus, the proposed approach offers a powerful and effective way to identify essential genes and proteins.

Novel human CRYGD rare variant in a Brazilian family with congenital cataract.

PURPOSE: To describe a novel polymorphism in the γD-crystallin (CRYGD) gene in a Brazilian family with congenital cataract. METHODS: A Brazilian four-generation family was analyzed. The proband had bilateral lamellar cataract and the phenotypes were classified by slit lamp examination. Genomic DNA was extracted from peripheral blood and coding regions and intron/exon boundaries of the αA-crystallin (CRYAA), γC-crystallin (CRYGC), and CRYGD genes were amplified by polymerase chain reaction and directly sequenced. RESULTS: Sequencing of the coding regions of CRYGD showed the presence of a heterozygous A→G transversion at c.401 position, which results in the substitution of a tyrosine to a cysteine (Y134C). The polymorphism was identified in three individuals, two affected and one unaffected. CONCLUSIONS: A novel rare variant in CRYGD (Y134C) was detected in a Brazilian family with congenital cataract. Because there is no segregation between the substitution and the phenotypes in this family, other genetic alterations are likely to be present.

Altered superoxide dismutase-1 activity and intercellular adhesion molecule 1 (ICAM-1) levels in patients with type 2 diabetes mellitus.

Inflammation and oxidative stress are linked to type 2 diabetes mellitus (T2DM). In this work, we analyzed patients' blood markers of antioxidant capacity, oxidative stress and inflammation in individuals with T2DM, in pre-diabetes state (pre-DM) and controls without diabetes. Patients were divided into three groups, according to glycated hemoglobin A1c (HbA1c): <7%, 7-9%, and >9%. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, total thiols, nitric oxide (•NO), tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule 1 (ICAM-1) levels of the individuals were measured. Plasma SOD activity was higher in T2DM subjects compared to the controls. While total thiols levels were lower in T2DM groups when compared to pre-DM, the values remained unchanged when compared to controls. ICAM-1 levels of T2DM groups were lower than in controls, while GPx activity, •NO, and TNF-α levels were similar among all groups. A positive correlation was found between SOD and HbA1c levels. Concluding, individuals with T2DM present altered SOD activity, total thiols, and ICAM-1 levels, which might contribute to further complications. There is a positive correlation between SOD activity and HbA1c levels. No apparent correlation exists between total thiols and ICAM-1 levels and with any other of the parameters evaluated in this study.

CYP1B1 gene analysis in primary congenital glaucoma Brazilian patients: novel mutations and association with poor prognosis.

PURPOSE: To determine the spectrum of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma, and to correlate the presence of alterations in the CYP1B1 gene sequence with clinical aspects of the disease. MATERIALS AND METHODS: Thirty nonrelated patients with primary congenital glaucoma were studied. Molecular analysis consisted of the codifying region sequencing (exons 2 and 3) and intron/exon boundaries. RESULTS: CYP1B1 gene mutations were present in 9 (30%) of the 30 patients. The structural changes in the CYP1B1 gene previously described in the literature and observed in our study were Q19X, P437L, A443G, g.4340delG, g.7901_79013delGAGTGCAGGCAGA, g.8182delG, and g.8214_8215delG. Three new mutations were observed: 4635delT, 4523delC, and L378Q, in addition to 3793T→C, R48G, A119S, L432V, D449D, and N453S polymorphisms. Patients carrying CYP1B1 gene mutations needed more surgical procedures to control intraocular pressure, either when both eyes were evaluated (P=0.003) or when the worst eye of the patient was analyzed (P=0.011). In relation to the number of affected eyes, all patients with mutations (n=9/9) developed bilateral glaucoma, whereas 11/21 patients without mutations in the CYP1B1 gene had bilateral glaucoma (P=0.013). CONCLUSIONS: In this group of primary congenital glaucoma patients, a 30% mutation frequency in the CYP1B1 gene was observed. The presence of mutations was associated with a more severe form of the disease, requiring more surgeries for intraocular pressure control and with a higher rate of bilateral cases.