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New evidence strongly discloses the pathogenesis of host-associated microbiomes in respiratory diseases. The microbiome dysbiosis modulates the lung's behavior and deteriorates the respiratory system's effective functioning. Several exogenous and environmental factors influence the development of asthma and chronic lung disease. The relationship between asthma and microbes is reasonably understood and yet to be investigated for more substantiation. The comorbidities such as SARS-CoV-2 further exacerbate the health condition of the asthma-affected individuals. This study examines the raw 16S rRNA sequencing data collected from the saliva and nasopharyngeal regions of pre-existing asthma (23) and non-asthma patients (82) infected by SARS-CoV-2 acquired from the public database. The experiment is designed in a two-fold pattern, analyzing the associativity between the samples collected from the saliva and nasopharyngeal regions. Later, investigates the microbial pathogenesis, its role in exacerbations of respiratory disease, and deciphering the diagnostic biomarkers of the target condition. LEfSE analysis identified that Actinobacteriota and Pseudomonadota are enriched in the SARS-CoV-2-non-asthma group and SARS-CoV-2 asthma group of the salivary microbiome, respectively. Random forest algorithm is trained with amplicon sequence variants (ASVs) attained better classification accuracy, ROC scores on nasal (84% and 87%) and saliva datasets (93% and 97.5%). Rothia mucilaginosa is less abundant, and Corynebacterium tuberculostearicum showed higher abundance in the SARS-CoV-2 asthma group. The increase in Streptococcus at the genus level in the SARS-CoV-2-asthma group is evidence of discriminating the subgroups. [ABSTRACT FROM AUTHOR]

Background: Understanding and predicting molecular basis of disease is one of the major challenges in modern biology and medicine. SNPs associated with complex disorders can create, destroy, or modify protein coding sites. Single amino acid substitutions in the ATM gene are the most common forms of genetic variations that account for various forms of cancer. However, the extent to which SNPs interferes with the gene regulation and affects cancer susceptibility remains largely unknown. Principal findings: We analyzed the deleterious nsSNPs associated with ATM gene based on different computational methods. An integrative scoring system and sequence conservation of amino acid residues was adapted for a priori nsSNP analysis of variants associated with cancer. We further extended our approach on SNPs that could potentially influence protein Post Translational Modifications in ATM gene. Significance: In the lack of adequate prior reports on the possible deleterious effects of nsSNPs, we have systematically analyzed and characterized the functional variants in both coding and non coding region that can alter the expression and function of ATM gene. In silico characterization of nsSNPs affecting ATM gene function can aid in better understanding of genetic differences in disease susceptibility. [ABSTRACT FROM AUTHOR]

Background: Elucidating the molecular dynamic behavior of Protein-DNA complex upon mutation is crucial in current genomics. Molecular dynamics approach reveals the changes on incorporation of variants that dictate the structure and function of Protein-DNA complexes. Deleterious mutations in APE1 protein modify the physicochemical property of amino acids that affect the protein stability and dynamic behavior. Further, these mutations disrupt the binding sites and prohibit the protein to form complexes with its interacting DNA. Principal Findings: In this study, we developed a rapid and cost-effective method to analyze variants in APE1 gene that are associated with disease susceptibility and evaluated their impacts on APE1-DNA complex dynamic behavior. Initially, two different in silico approaches were used to identify deleterious variants in APE1 gene. Deleterious scores that overlap in these approaches were taken in concern and based on it, two nsSNPs with IDs rs61730854 (I64T) and rs1803120 (P311S) were taken further for structural analysis. Significance: Different parameters such as RMSD, RMSF, salt bridge, H-bonds and SASA applied in Molecular dynamic study reveals that predicted deleterious variants I64T and P311S alters the structure as well as affect the stability of APE1-DNA interacting functions. This study addresses such new methods for validating functional polymorphisms of human APE1 which is critically involved in causing deficit in repair capacity, which in turn leads to genetic instability and carcinogenesis. [ABSTRACT FROM AUTHOR]

This paper depicts the first report from an Indian population on the association between the variant Arg399Gln of XRCC1 locus in the DNA repair system and schizophrenia, the debilitating disease that affects 1% of the world population. Genotypic analysis of a total of 523 subjects (260 patients and 263 controls) revealed an overwhelming presence of Gln399Gln in the case subjects against the controls (P < 0.0068), indicating significant level of association of this nsSNP with schizophrenia; the Gln399 allele frequency was also perceptibly more in cases than in controls (p < 0.003; OR = 1.448). The results of the genotypic studies were further validated using pathogenicity and stability prediction analysis employing computational tools [I-Mutant Suite, iStable, PolyPhen2, SNAP, and PROVEAN], with a view toassess the magnitude of deleteriousness of the mutation. The pathogenicity analysis reveals that the nsSNP could be deleterious inasmuch as it could affect the functionality of the gene, and interfere with protein function. Molecular dynamics simulation of 60ns was performed using GROMACS to analyse structural change due to a mutation (Arg399Gln) that was never examined before. RMSD, RMSF, hydrogen bonds, radius of gyration and SASA analysis showedthe existence of asignificant difference between the native and the mutant protein. The present study gives astrong indication that the XRCC1 locus deserves serious attention, as it could be a potential candidatecontributing to the etio-pathogenesis of the disease. [ABSTRACT FROM AUTHOR]