Robust Identification of Differential Gene Expression Patterns from Multiple Transcriptomics Datasets for Early Diagnosis, Prognosis, and Therapies for Breast Cancer.

Background and Objectives: Breast cancer (BC) is one of the major causes of cancer-related death in women globally. Proper identification of BC-causing hub genes (HubGs) for prognosis, diagnosis, and therapies at an earlier stage may reduce such death rates. However, most of the previous studies detected HubGs through non-robust statistical approaches that are sensitive to outlying observations. Therefore, the main objectives of this study were to explore BC-causing potential HubGs from robustness viewpoints, highlighting their early prognostic, diagnostic, and therapeutic performance. Materials and Methods: Integrated robust statistics and bioinformatics methods and databases were used to obtain the required results. Results: We robustly identified 46 common differentially expressed genes (cDEGs) between BC and control samples from three microarrays (GSE26910, GSE42568, and GSE65194) and one scRNA-seq (GSE235168) dataset. Then, we identified eight cDEGs (COL11A1, COL10A1, CD36, ACACB, CD24, PLK1, UBE2C, and PDK4) as the BC-causing HubGs by the protein-protein interaction (PPI) network analysis of cDEGs. The performance of BC and survival probability prediction models with the expressions of HubGs from two independent datasets (GSE45827 and GSE54002) and the TCGA (The Cancer Genome Atlas) database showed that our proposed HubGs might be considered as diagnostic and prognostic biomarkers, where two genes, COL11A1 and CD24, exhibit better performance. The expression analysis of HubGs by Box plots with the TCGA database in different stages of BC progression indicated their early diagnosis and prognosis ability. The HubGs set enrichment analysis with GO (Gene ontology) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways disclosed some BC-causing biological processes, molecular functions, and pathways. Finally, we suggested the top-ranked six drug molecules (Suramin, Rifaximin, Telmisartan, Tukysa Tucatinib, Lynparza Olaparib, and TG.02) for the treatment of BC by molecular docking analysis with the proposed HubGs-mediated receptors. Molecular docking analysis results also showed that these drug molecules may inhibit cancer-related post-translational modification (PTM) sites (Succinylation, phosphorylation, and ubiquitination) of hub proteins. Conclusions: This study's findings might be valuable resources for diagnosis, prognosis, and therapies at an earlier stage of BC.

Robust identification of common genomic biomarkers from multiple gene expression profiles for the prognosis, diagnosis, and therapies of pancreatic cancer.

Pancreatic cancer (PC) is one of the leading causes of cancer-related death globally. So, identification of potential molecular signatures is required for diagnosis, prognosis, and therapies of PC. In this study, we detected 71 common differentially expressed genes (cDEGs) between PC and control samples from four microarray gene-expression datasets (GSE15471, GSE16515, GSE71989, and GSE22780) by using robust statistical and machine learning approaches, since microarray gene-expression datasets are often contaminated by outliers due to several steps involved in the data generating processes. Then we detected 8 cDEGs (ADAM10, COL1A2, FN1, P4HB, ITGB1, ITGB5, ANXA2, and MYOF) as the PC-causing key genes (KGs) by the protein-protein interaction (PPI) network analysis. We validated the expression patterns of KGs between case and control samples by box plot analysis with the TCGA and GTEx databases. The proposed KGs showed high prognostic power with the random forest (RF) based prediction model and Kaplan-Meier-based survival probability curve. The KGs regulatory network analysis detected few transcriptional and post-transcriptional regulators for KGs. The cDEGs-set enrichment analysis revealed some crucial PC-causing molecular functions, biological processes, cellular components, and pathways that are associated with KGs. Finally, we suggested KGs-guided five repurposable drug molecules (Linsitinib, CX5461, Irinotecan, Timosaponin AIII, and Olaparib) and a new molecule (NVP-BHG712) against PC by molecular docking. The stability of the top three protein-ligand complexes was confirmed by molecular dynamic (MD) simulation studies. The cross-validation and some literature reviews also supported our findings. Therefore, the finding of this study might be useful resources to the researchers and medical doctors for diagnosis, prognosis and therapies of PC by the wet-lab validation.

Exploring Core Genes by Comparative Transcriptomics Analysis for Early Diagnosis, Prognosis, and Therapies of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers with a high mortality rate. Early diagnosis and therapies for CRC may reduce the mortality rate. However, so far, no researchers have yet investigated core genes (CGs) rigorously for early diagnosis, prognosis, and therapies of CRC. Therefore, an attempt was made in this study to explore CRC-related CGs for early diagnosis, prognosis, and therapies. At first, we identified 252 common differentially expressed genes (cDEGs) between CRC and control samples based on three gene-expression datasets. Then, we identified ten cDEGs (AURKA, TOP2A, CDK1, PTTG1, CDKN3, CDC20, MAD2L1, CKS2, MELK, and TPX2) as the CGs, highlighting their mechanisms in CRC progression. The enrichment analysis of CGs with GO terms and KEGG pathways revealed some crucial biological processes, molecular functions, and signaling pathways that are associated with CRC progression. The survival probability curves and box-plot analyses with the expressions of CGs in different stages of CRC indicated their strong prognostic performance from the earlier stage of the disease. Then, we detected CGs-guided seven candidate drugs (Manzamine A, Cardidigin, Staurosporine, Sitosterol, Benzo[a]pyrene, Nocardiopsis sp., and Riccardin D) by molecular docking. Finally, the binding stability of four top-ranked complexes (TPX2 vs. Manzamine A, CDC20 vs. Cardidigin, MELK vs. Staurosporine, and CDK1 vs. Riccardin D) was investigated by using 100 ns molecular dynamics simulation studies, and their stable performance was observed. Therefore, the output of this study may play a vital role in developing a proper treatment plan at the earlier stages of CRC.

Bioinformatics-based investigation on the genetic influence between SARS-CoV-2 infections and idiopathic pulmonary fibrosis (IPF) diseases, and drug repurposing.

Some recent studies showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and idiopathic pulmonary fibrosis (IPF) disease might stimulate each other through the shared genes. Therefore, in this study, an attempt was made to explore common genomic biomarkers for SARS-CoV-2 infections and IPF disease highlighting their functions, pathways, regulators and associated drug molecules. At first, we identified 32 statistically significant common differentially expressed genes (cDEGs) between disease (SARS-CoV-2 and IPF) and control samples of RNA-Seq profiles by using a statistical r-package (edgeR). Then we detected 10 cDEGs (CXCR4, TNFAIP3, VCAM1, NLRP3, TNFAIP6, SELE, MX2, IRF4, UBD and CH25H) out of 32 as the common hub genes (cHubGs) by the protein-protein interaction (PPI) network analysis. The cHubGs regulatory network analysis detected few key TFs-proteins and miRNAs as the transcriptional and post-transcriptional regulators of cHubGs. The cDEGs-set enrichment analysis identified some crucial SARS-CoV-2 and IPF causing common molecular mechanisms including biological processes, molecular functions, cellular components and signaling pathways. Then, we suggested the cHubGs-guided top-ranked 10 candidate drug molecules (Tegobuvir, Nilotinib, Digoxin, Proscillaridin, Simeprevir, Sorafenib, Torin 2, Rapamycin, Vancomycin and Hesperidin) for the treatment against SARS-CoV-2 infections with IFP diseases as comorbidity. Finally, we investigated the resistance performance of our proposed drug molecules compare to the already published molecules, against the state-of-the-art alternatives publicly available top-ranked independent receptors by molecular docking analysis. Molecular docking results suggested that our proposed drug molecules would be more effective compare to the already published drug molecules. Thus, the findings of this study might be played a vital role for diagnosis and therapies of SARS-CoV-2 infections with IPF disease as comorbidity risk.

Prediction of serine phosphorylation sites mapping on Schizosaccharomyces Pombe by fusing three encoding schemes with the random forest classifier.

Serine phosphorylation is one type of protein post-translational modifications (PTMs), which plays an essential role in various cellular processes and disease pathogenesis. Numerous methods are used for the prediction of phosphorylation sites. However, the traditional wet-lab based experimental approaches are time-consuming, laborious, and expensive. In this work, a computational predictor was proposed to predict serine phosphorylation sites mapping on Schizosaccharomyces pombe (SP) by the fusion of three encoding schemes namely k-spaced amino acid pair composition (CKSAAP), binary and amino acid composition (AAC) with the random forest (RF) classifier. So far, the proposed method is firstly developed to predict serine phosphorylation sites for SP. Both the training and independent test performance scores were used to investigate the success of the proposed RF based fusion prediction model compared to others. We also investigated their performances by 5-fold cross-validation (CV). In all cases, it was observed that the recommended predictor achieves the largest scores of true positive rate (TPR), true negative rate (TNR), accuracy (ACC), Mathew coefficient of correlation (MCC), Area under the ROC curve (AUC) and pAUC (partial AUC) at false positive rate (FPR) = 0.20. Thus, the prediction performance as discussed in this paper indicates that the proposed approach may be a beneficial and motivating computational resource for predicting serine phosphorylation sites in the case of Fungi. The online interface of the software for the proposed prediction model is publicly available at http://mollah-bioinformaticslab-stat.ru.ac.bd/PredSPS/ .