With the advent of high-throughput technologies leading to big data generation, increasing number of gene signatures are being published to predict various features of diseases such as prognosis and patient survival. However, to use these signatures for identifying therapeutic targets, use of additional bioinformatic tools is indispensible part of research. Here, we have generated a pipeline comprised of nearly 15 bioinformatic tools and enrichment statistical methods to propose and validate a drug combination strategy from already approved drugs and present our approach using published pan-cancer epithelial-mesenchymal transition (EMT) signatures as a case study. We observed that histone deacetylases were critical targets to tune expression of multiple epithelial versus mesenchymal genes. Moreover, SRC and IKBK were the principal intracellular kinases regulating multiple signaling pathways. To confirm the anti-EMT efficacy of the proposed target combination in silico, we validated expression of targets in mesenchymal versus epithelial subtypes of ovarian cancer. Additionally, we inhibited the pinpointed proteins in vitro using an invasive lung cancer cell line. We found that whereas low-dose mono-therapy failed to limit cell dispersion from collagen spheroids in a microfluidic device as a metric of EMT, the combination fully inhibited dissociation and invasion of cancer cells toward cocultured endothelial cells. Given the approval status and safety profiles of the suggested drugs, the proposed combination set can be considered in clinical trials.
Conventional proteomics has discovered a wide gap between protein sequences and biological functions. The third generation of proteomics was provoked to bridge this gap. Targeted and untargeted post-translational modification (PTM) studies are the most important parts of today’s proteomics. Considering the expensive and time-consuming nature of experimental methods, computational methods are developed to study, analyze, predict, count and compute the PTM annotations on proteins. The enrichment analysis softwares are among the common computational biology and bioinformatic software packages. The focus of such softwares is to find the probability of occurrence of the desired biological features in any arbitrary list of genes/proteins. We introduce Post-translational modification Enrichment Integration and Matching Analysis (PEIMAN) software to explore more probable and enriched PTMs on proteins. Here, we also represent the statistics of detected PTM terms used in enrichment analysis in PEIMAN software based on the latest released version of UniProtKB/Swiss-Prot. These results, in addition to giving insight to any given list of proteins, could be useful to design targeted PTM studies for identification and characterization of special chemical groups.Database URL:
http://bs.ipm.ir/softwares/PEIMAN/
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.