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Assessing computational predictions of the phenotypic effect of cystathionine‐beta‐synthase variants
Laura Kasak Constantina Bakolitsa Zhiqiang Hu Changhua Yu Jasper Rine Dago F. Dimster‐Denk Gaurav Pandey Greet De Baets Yana Bromberg Chen Cao Emidio Capriotti Rita Casadio Joost Van Durme Manuel Giollo Rachel Karchin Panagiotis Katsonis Emanuela Leonardi Olivier Lichtarge Pier Luigi Martelli David Masica Sean D. Mooney Ayodeji Olatubosun Predrag Radivojac Frederic Rousseau Lipika R. Pal Castrense Savojardo Joost Schymkowitz Janita Thusberg Silvio C.E. Tosatto Mauno Vihinen Jouni Vliaho Susanna Repo John Moult Steven E. Brenner Iddo Friedberg 《Human mutation》2019,40(9):1530-1545
Accurate prediction of the impact of genomic variation on phenotype is a major goal of computational biology and an important contributor to personalized medicine. Computational predictions can lead to a better understanding of the mechanisms underlying genetic diseases, including cancer, but their adoption requires thorough and unbiased assessment. Cystathionine‐beta‐synthase (CBS) is an enzyme that catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine, and in which variations are associated with human hyperhomocysteinemia and homocystinuria. We have created a computational challenge under the CAGI framework to evaluate how well different methods can predict the phenotypic effect(s) of CBS single amino acid substitutions using a blinded experimental data set. CAGI participants were asked to predict yeast growth based on the identity of the mutations. The performance of the methods was evaluated using several metrics. The CBS challenge highlighted the difficulty of predicting the phenotype of an ex vivo system in a model organism when classification models were trained on human disease data. We also discuss the variations in difficulty of prediction for known benign and deleterious variants, as well as identify methodological and experimental constraints with lessons to be learned for future challenges. 相似文献
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Luis Eduardo Almeida Adam Sorenson Kyle Hresko Seth Butcher Rosalia Leonardi Carla Loreto 《Cranio : the journal of craniomandibular practice》2019,37(3):175-180
Objective Temporomandibular joint dysfunction (TMD) may affect a patient’s quality of life, and one of the etiologies can be anterior disc displacement with reduction (ADDwR) and anterior disc displacement without reduction (ADDWoR). Interleukin 1 Receptor 1 (IL-1R1) is a membrane receptor that plays an important role on initiating immune and inflammatory response by binding the agonists ligands of IL-1 alpha and IL-1 beta. Therefore, the aim of this study was to evaluate, through immunohistochemical analysis, the association of IL-1R1 with TMD.
Methods Thirty-nine human disc samples were collected and composed three different groups: ADDwR (n = 19), ADDwoR (n = 12), and control group (n = 8). The samples were immunostained with IL-1R1 antibody and evaluated on both quantity and intensity of staining.
Results There was a statistically significant difference (p < 0.05) between the control and test groups for both quantity and intensity of staining.
Conclusion IL1-R1 was associated with ADDwR and ADDwoR in TMD discs of humans. 相似文献
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Lo Muzio L Santarelli A Caltabiano R Rubini C Pieramici T Fior A Trevisiol L Carinci F Leonardi R Bufo P Lanzafame S Piattelli A 《International journal of oral and maxillofacial surgery》2005,34(6):668-673
A total of 123 cases of odontogenic cysts, distributed as follows: 30 follicular (FC), 35 radicular (RC), 53 keratocysts, 1 glandular odontogenic and 4 calcifying odontogenic cysts, were analysed by immunohistochemistry for expression of p63, a component of p53 protein family. In RCs p63 positivity was not only in basal and parabasal layers but also in the intermediate layer and about 1/3 of cases displayed a percentage of stained cells comprised between 0 and <5%, and about 2/3 between >5% and <50%. In FCs positivity was confined to basal and parabasal layers of the epithelium and in the majority of FCs the stained cells were comprised between 0 and <5%. OKCs displayed the most intense and diffuse p63 labeling. In conclusion, these data suggest that p63 expression may be useful to identify cysts type with more aggressive and invasive phenotype supporting the hypothesis of a suprabasal proliferative compartment in OKCs. 相似文献
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The cleaning efficiency and the quality of the surgical preparation is mainly conditioned by root canal anatomy, the instruments and the technique employed. The purpose of the present study was to evaluate the extent of straightening of curved root canals and the changes in endodontic anatomy caused by the use of Flex-R, Onyx-R and Nitiflex files with the balanced forces technique. Sixty mandibular molars were selected for evaluation of angulation and transportation. Pre and post instrumentation radiographs were taken of the mesiodistal and buccolingual aspects of each tooth. The radiographs were projected on a transparent sheet, the contours of each tooth and file were outlined and the canal curvature was measured. Pre and post instrumentation tracings were overlaid and the extent of transportation was measured with a micrometric caliper. Statistical analysis of the data was performed employing Student's "t" test, Analysis of Variance and Bonferroni's test. The results showed that all the instruments reduced canal curvature significantly. Transportation in the mesiodistal direction did not reach statistical significance whereas transportation in the buccolingual direction was statistically significant. 相似文献