RESUMO
Cervical cancer is one of the most severe threats to women worldwide and holds fourth rank in lethality. It is estimated that 604, 127 cervical cancer cases have been reported in 2020 globally. With advancements in high throughput technologies and bioinformatics, several cervical candidate genes have been proposed for better therapeutic strategies. In this paper, we intend to prioritize the candidate genes that are involved in cervical cancer progression through a fractal time series-based cross-correlations approach. we apply the chaos game representation theory combining a two-dimensional multifractal detrended cross-correlations approach among the known and candidate genes involved in cervical cancer progression to prioritize the candidate genes. We obtained 16 candidate genes that showed cross-correlation with known cancer genes. Functional enrichment analysis of the candidate genes shows that they involve GO terms: biological processes, cell-cell junction assembly, cell-cell junction organization, regulation of cell shape, cortical actin cytoskeleton organization, and actomyosin structure organization. KEGG pathway analysis revealed genes' role in Rap1 signaling pathway, ErbB signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, Acute myeloid leukemia, chronic myeloid leukemia, Breast cancer, Thyroid cancer, Bladder cancer, and Gastric cancer. Further, we performed survival analysis and prioritized six genes CDH2, PAIP1, BRAF, EPB41L3, OSMR, and RUNX1 as potential candidate genes for cervical cancer that has a crucial role in tumor progression. We found that our study through this integrative approach an efficient tool and paved a new way to prioritize the candidate genes and these genes could be evaluated experimentally for potential validation. We suggest this may be useful in analyzing the nucleotide sequences and protein sequences for clustering, classification, class affiliation, etc.
RESUMO
In biological network analysis, identifying key molecules plays a decisive role in the development of potential diagnostic and therapeutic candidates. Among various approaches of network analysis, network vulnerability analysis is quite important, as it assesses significant associations between topological properties and the functional essentiality of a network. Similarly, some node centralities are also used to screen out key molecules. Among these node centralities, escape velocity centrality (EVC), and its extended version (EVC+) outperform others, viz., Degree, Betweenness, and Clustering coefficient. Keeping this in mind, we aimed to develop a first-of-its-kind R package named NetVA, which analyzes networks to identify key molecular players (individual proteins and protein pairs/triplets) through network vulnerability and EVC+-based approaches. To demonstrate the application and relevance of our package in network analysis, previously published and publicly available protein-protein interactions (PPIs) data of human breast cancer were analyzed. This resulted in identifying some most important proteins. These included essential proteins, non-essential proteins, hubs, and bottlenecks, which play vital roles in breast cancer development. Thus, the NetVA package, available at https://github.com/kr-swapnil/NetVA with a detailed tutorial to download and use, assists in predicting potential candidates for therapeutic and diagnostic purposes by exploring various topological features of a disease-specific PPIs network.Communicated by Ramaswamy H. Sarma.