Alam, S. | Search bioRxiv

bioRxiv2018

Prediction of Deleterious Single Nucleotide Polymorphisms in Human p53 Gene

With a variety of accessible Single Nucleotide Polymorphisms (SNPs) data on human p53 gene, this investigation is intended to deal with detrimental SNPs in p53 gene by executing diverse valid computational tools, including Filter, SIFT, PredictSNP, Fathmm, UTRScan, ConSurf, Phyre, Tm-Adjust, I-Mutant, Task Seek after practical and basic appraisal, dissolvable openness, atomic progression, and analysing the energy minimization. Of 581 p53 SNPs, 420 SNPs are found to be missense or non-synonymous and 435 SNPs are in the 3 prime UTR and 112 SNPs are of every 5 prime UTR from which 16 non synonymous SNPs (nsSNPs) as non-tolerable while PredictSNP package predicted 14 (taking consideration SNP colored green by two or more than 2 analyses is neutral). By concentrating on six bioinformatics tools of various dimensions a combined output is generated where 14 nsSNPs are prone to exert a deleterious effect. By using diverse SNP analysing tools we have found 5 missense SNPs in the 3 crucial amino acids position in the DNA binding domain. The underlying discoveries are fortified by I-Mutant and Project HOPE. The ExPASy-PROSITE tools characterized whether the mutations located in the functional part of the protein or not. This study provides a decisive outcome concluding the accessible SNPs information by recognizing the five harming nsSNPs: rs28934573 (S241F), rs11540652 (R248Q), rs121913342 (R248W), rs121913343 (R273C) and rs28934576 (R273H). The findings of this investigation recognize the detrimental nsSNPs which enhance the danger of various kinds of oncogenesis in patients of different populations in genome-wide studies (GWS).

bioinformatics↗

bioRxiv2018

The Effect of Productive HPV16 Infection on Global Gene Expression of Cervical Epithelium

Human papillomavirus (HPV) infection is the worlds most common sexually transmitted infection, and is responsible for most cases of cervical cancer. Previous studies of global gene expression changes induced by HPV infection have focused on the cancerous stages of infection, and therefore, not much is known about global gene expression changes at early pre-neoplastic stages of infection. We show for the first time, global gene expression changes of early stage HPV16 infection in cervical tissue using 3-dimensional organotypic raft cultures that produce high levels of progeny virions.\n\ncDNA microarray analysis showed that a total of 594 genes were upregulated and 651 genes were downregulated at least 1.5-fold with HPV16 infection. Gene ontology analysis showed that biological processes including cell cycle progression and DNA metabolism were upregulated, while skin development, immune response, and cell death were downregulated with HPV16 infection in cervical keratinocytes. Individual genes were selected for validation at the transcriptional and translational levels including UBC, which was central to the protein association network of immune response genes, and top downregulated genes RPTN, SERPINB4, KRT23, and KLK8. In particular, KLK8 and SERPINB4 have shown to be upregulated in cancer, which contrasts our results.\n\nOrganotypic raft cultures that allow full progression of the HPV life-cycle have allowed us to identify novel gene modulations and potential therapeutic targets of early stage HPV infection in cervical tissue. Additionally, our results suggest that early stage productive infection and cancerous stages of infection are distinct disease states expressing different transcriptomes.\n\nImportancePersistent HPV infection is responsible for most cases of cervical cancer. Transition from precancerous to cancerous stages of HPV infection is marked by a significant reduction in virus production. Most global gene expression studies of HPV infection have focused on the cancerous stages. Therefore, little is known about global gene expression changes at precancerous stages. For the first time, we measured global gene expression changes at precancerous stages of HPV16 infection in human cervical tissue producing high levels of virus. We identified a group of genes that are typically overexpressed in cancerous stages to be significantly downregulated at the precancerous stage. Moreover, we identified significantly modulated genes that have not yet been studied in the context of HPV infection. Studying the role of these genes in HPV infection will help us understand what drives the transition from precancerous to cancerous stages, and may lead to development of new therapeutic targets.

genomics↗