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Emel Rothzerg Jiake Xu David Wood Sulev Kks 《Experimental biology and medicine (Maywood, N.J.)》2021,246(19):2072
The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project aims to determine molecular changes that drive childhood cancers, including osteosarcoma. The main purpose of the program is to use the open-source database to develop novel, effective, and less toxic therapies. We downloaded TARGET-OS RNA-Sequencing data through R studio and merged the mRNA expression of genes with clinical information (vital status, survival time and gender). Further, we analyzed differential gene expressions between dead and alive patients based on TARGET-OS project. By this study, we found 5758 differentially expressed genes between deceased and alive patients with a false discovery rate below 0.05; 4469 genes were upregulated in deceased patients compared to alive, whereas 1289 genes were downregulated. The survival-related genes were obtained using Kaplan–Meier survival analysis and Cox univariate regression (KM < 0.05 and Cox P-value < 0.05). Out of 5758 differentially expressed genes, only 217 have been associated with overall survival. Eight survival-related downregulated genes (ERCC4, CLUAP1, CTNNBIP1, GCA, RAB40C, SIRPA, USP11, and TCN2) and four survival-related upregulated genes (MUC1, COL13A1, JAG2 and KAZALD1) were selected for further analysis as potential independent prognostic candidate genes. This study may help to discover novel prognostic markers and potential therapeutic targets for osteosarcoma. 相似文献
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A Molecular Docking and Dynamics Approach to Screen Potent Inhibitors Against Fosfomycin Resistant Enzyme in Clinical Klebsiella pneumoniae
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Simulation Based Investigation of Deleterious nsSNPs in ATXN2 Gene and Its Structural Consequence Toward Spinocerebellar Ataxia
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Siddharth Sinha Sharad Verma Aditi Singh Pallavi Somvanshi Abhinav Grover 《Journal of cellular biochemistry》2018,119(1):499-510
Spinocerebellar degeneration, termed as ataxia is a neurological disorder of central nervous system, characterized by limb in‐coordination and a progressive gait. The patient also demonstrates specific symptoms of muscle weakness, slurring of speech, and decreased vibration senses. Expansion of polyglutamine trinucleotide (CAG) within ATXN2 gene with 35 or more repeats, results in spinocerebellar ataxia type‐2. Protein ataxin‐2 coded by ATXN2 gene has been reported to have a crucial role in translation of the genetic information through sequestering the histone acetyl transferases (HAT) resulting in a state of hypo‐acetylation. In the present study, we have evaluated the outcome for 122 non synonymous single nucleotide polymorphisms (nsSNPs) reported within ATXN2 gene through computational tools such as SIFT, PolyPhen 2.0, PANTHER, I‐mutant 2.0, Phd‐SNP, Pmut, MutPred. The apo and mutant (L305V and Q339L) form of structures for the ataxin‐2 protein were modeled for gaining insights toward 3D spatial arrangement. Further, molecular dynamics simulations and structural analysis were performed to observe the brunt of disease associated nsSNPs toward the strength and secondary properties of ataxin‐2 protein structure. Our results showed that, L305V is a highly deleterious and disease causing point substitution. Analysis based on RMSD, RMSF, Rg, SASA, number of hydrogen bonds (NH bonds), covariance matrix trace, projection analysis for eigen vector demonstrated a significant instability and conformation along with rise in mutant flexibility values in comparison to the apo form of ataxin‐2 protein. The study provides a blue print of computational methodologies to examine the ataxin‐blend SNPs. J. Cell. Biochem. 119: 499–510, 2018. © 2017 Wiley Periodicals, Inc. 相似文献
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