Integrative Systems Biology Approaches to Identify Potential Biomarkers and Pathways of Cervical Cancer

Nowadays, cervical cancer (CC) is treated as the leading cancer among women throughout the world. Despite effective vaccination and improved surgery and treatment, CC retains its fatality rate of about half of the infected population globally. The major screening biomarkers and therapeutic target identification have now become a global concern. In the present study, we have employed systems biology approaches to retrieve the potential biomarkers and pathways from transcriptomic profiling. Initially, we have identified 76 of each up-regulated and down-regulated gene from a total of 4643 differentially expressed genes. The up-regulatory genes mainly concentrate on immune-inflammatory responses, and the down-regulatory genes are on receptor binding and gamma-glutamyltransferase. The involved pathways associated with these genes were also assessed through pathway enrichment, and we mainly focused on different cancer pathways, immunoresponse, and cell cycle pathways. After the subsequent enrichment of these genes, we have identified 12 hub genes, which play a crucial role in CC and are verified by expression profile analysis. From our study, we have found that genes LILRB2 and CYBB play crucial roles in CC, as reported here for the first time. Furthermore, the survivability of the hub genes was also assessed, and among them, finally, CXCR4 has been identified as one of the most potential differentially expressed genes that might play a vital role in the survival of CC patients. Thus, CXCR4 could be used as a prognostic and/or diagnostic biomarker and a drug target for CC

Hypothesis Homology modeling and assigned functional annotation of an uncharacterized antitoxin protein from Streptomyces xinghaiensis

Abstract: Streptomyces xinghaiensis is a Gram-positive, aerobic and non-motile bacterium. The bacterial genome is known. Therefore, it is of interest to study the uncharacterized proteins in the genome. An uncharacterized protein (gi|518540893|86 residues) in the genome was selected for a comprehensive computational sequence-structure-function analysis using available data and tools. Subcellular localization of the targeted protein with conserved residues and assigned secondary structures is documented. Sequence homology search against the protein data bank (PDB) and non-redundant GenBank proteins using BLASTp showed different homologous proteins with known antitoxin function. A homology model of the target protein was developed using a known template (PDB ID: 3CTO:A) with 62% sequence similarity in HHpred after assessment using programs PROCHECK and QMEAN6. The predicted active site using CASTp is analyzed for assigned anti-toxin function. This information finds specific utility in annotating the said uncharacterized protein in the bacterial genome. Keywords: antitoxin, homology modeling, active-site residues, prediction, hypothetical protein, Streptomyces xinghaiensis Background: Streptomyces are soil-conquering gram-positive bacteria and a member of the order of Actinomycetales [1]. Streptomyces xinghaiensis, a novel species of Streptomyces, was isolated from a marine sediment sample collected from Xinghai Bay, Dalian, China [2]. The S. xinghaiensis draft genome contains 7,618,725 bp with a GC content of 72.5%, representing approximately 92.7% of the 8.2-Mb estimated size of the genome. Analysis of the genome revealed a number of genes related to the biosynthesis of secondary metabolites. At least 15 clusters involved in secondary metabolism were identified; these include one gene cluster that highly resembles the gene cluster of ribostamycin [3], an amino-glycoside antibiotic. Toxinantitoxin (TA) system was widely adopted in many genomes like bacteria and archaea and is usually recognized as a maintenance or stability mediator [4, 5]. Although, the exact role of this system in the genome is not clear but, acts as sentinels against DNA loss and various stress managemen