Identification of genetic biomarkers, drug targets and agents for respiratory diseases utilising integrated bioinformatics approaches.

Respiratory diseases (RD) are significant public health burdens and malignant diseases worldwide. However, the RD-related biological information and interconnection still need to be better understood. Thus, this study aims to detect common differential genes and potential hub genes (HubGs), emphasizing their actions, signaling pathways, regulatory biomarkers for diagnosing RD and candidate drugs for treating RD. In this paper we used integrated bioinformatics approaches (such as, gene ontology (GO) and KEGG pathway enrichment analysis, molecular docking, molecular dynamic simulation and network-based molecular interaction analysis). We discovered 73 common DEGs (CDEGs) and ten HubGs (ATAD2B, PPP1CB, FOXO1, AKT3, BCR, PDE4D, ITGB1, PCBP2, CD44 and SMARCA2). Several significant functions and signaling pathways were strongly related to RD. We recognized six transcription factor (TF) proteins (FOXC1, GATA2, FOXL1, YY1, POU2F2 and HINFP) and five microRNAs (hsa-mir-218-5p, hsa-mir-335-5p, hsa-mir-16-5p, hsa-mir-106b-5p and hsa-mir-15b-5p) as the important transcription and post-transcription regulators of RD. Ten HubGs and six major TF proteins were considered drug-specific receptors. Their binding energy analysis study was carried out with the 63 drug agents detected from network analysis. Finally, the five complexes (the PDE4D-benzo[a]pyrene, SMARCA2-benzo[a]pyrene, HINFP-benzo[a]pyrene, CD44-ketotifen and ATAD2B-ponatinib) were selected for RD based on their strong binding affinity scores and stable performance as the most probable repurposable protein-drug complexes. We believe our findings will give readers, wet-lab scientists, and pharmaceuticals a thorough grasp of the biology behind RD.

Network based approach to identify interactions between Type 2 diabetes and cancer comorbidities.

High blood sugar and insulin insensitivity causes the lifelong chronic metabolic disease called Type 2 diabetes (T2D) which has a higher chance of developing different malignancies. T2D with comorbidities like Cancers can make normal medications for those disorders more difficult. There may be a significant correlation between comorbidities and have an impact on one another's health. These associations may be due to a number of direct and indirect mechanisms. Such molecular mechanisms that underpin T2D and cancer are yet unknown. However, the large volumes of data available on these diseases allowed us to use analytical tools for uncovering their interrelated pathways. Here, we tried to present a system for investigating potential comorbidity relationships between T2D and Cancer disease by looking at the molecular processes involved, analyzing a huge number of freely accessible transcriptomic datasets of various disorders using bioinformatics. Using semantic similarity and gene set enrichment analysis, we created an informatics pipeline that evaluates and integrates Gene Ontology (GO), expression of genes, and biological process data. We discovered genes that are common in T2D and Cancer along with molecular pathways and GOs. We compared the top 200 Differentially Expressed Genes (DEGs) from each selected T2D and cancer dataset and found the most significant common genes. Among all the common genes 13 genes were found most frequent. We also found 4 common GO terms: GO:0000003, GO:0000122, GO:0000165, and GO:0000278 among all the common GO terms between T2d and different cancers. Using these genes and GO term semantic similarity, we calculated the distance between these two diseases. The semantic similarity results of our study showed a higher association of Liver Cancer (LiC), Breast Cancer (BreC), Colorectal Cancer (CC), and Bladder Cancer (BlaC) with T2D. Furthermore we found KIF4A, NUSAP1, CENPF, CCNB1, TOP2A, CCNB2, RRM2, HMMR, NDC80, NCAPG, and IGFBP5 common hub proteins among different cancers correlated to T2D. AGE-RAGE signaling pathway in diabetic complications, Osteoclast differentiation, TNF signaling pathway, IL-17 signaling pathway, p53 signaling pathway, MAPK signaling pathway, Human T-cell leukemia virus 1 infection, and Non-alcoholic fatty liver disease are the 8 most significant pathways found among 18 common pathways between T2D and selected cancers. As a result of our technique, we now know more about disease pathways that are critical between T2D and cancer.

Cancer Classification Utilizing Voting Classifier with Ensemble Feature Selection Method and Transcriptomic Data.

Biomarker-based cancer identification and classification tools are widely used in bioinformatics and machine learning fields. However, the high dimensionality of microarray gene expression data poses a challenge for identifying important genes in cancer diagnosis. Many feature selection algorithms optimize cancer diagnosis by selecting optimal features. This article proposes an ensemble rank-based feature selection method (EFSM) and an ensemble weighted average voting classifier (VT) to overcome this challenge. The EFSM uses a ranking method that aggregates features from individual selection methods to efficiently discover the most relevant and useful features. The VT combines support vector machine, k-nearest neighbor, and decision tree algorithms to create an ensemble model. The proposed method was tested on three benchmark datasets and compared to existing built-in ensemble models. The results show that our model achieved higher accuracy, with 100% for leukaemia, 94.74% for colon cancer, and 94.34% for the 11-tumor dataset. This study concludes by identifying a subset of the most important cancer-causing genes and demonstrating their significance compared to the original data. The proposed approach surpasses existing strategies in accuracy and stability, significantly impacting the development of ML-based gene analysis. It detects vital genes with higher precision and stability than other existing methods.

A Novel Hybrid Approach for Classifying Osteosarcoma Using Deep Feature Extraction and Multilayer Perceptron.

Osteosarcoma is the most common type of bone cancer that tends to occur in teenagers and young adults. Due to crowded context, inter-class similarity, inter-class variation, and noise in H&E-stained (hematoxylin and eosin stain) histology tissue, pathologists frequently face difficulty in osteosarcoma tumor classification. In this paper, we introduced a hybrid framework for improving the efficiency of three types of osteosarcoma tumor (nontumor, necrosis, and viable tumor) classification by merging different types of CNN-based architectures with a multilayer perceptron (MLP) algorithm on the WSI (whole slide images) dataset. We performed various kinds of preprocessing on the WSI images. Then, five pre-trained CNN models were trained with multiple parameter settings to extract insightful features via transfer learning, where convolution combined with pooling was utilized as a feature extractor. For feature selection, a decision tree-based RFE was designed to recursively eliminate less significant features to improve the model generalization performance for accurate prediction. Here, a decision tree was used as an estimator to select the different features. Finally, a modified MLP classifier was employed to classify binary and multiclass types of osteosarcoma under the five-fold CV to assess the robustness of our proposed hybrid model. Moreover, the feature selection criteria were analyzed to select the optimal one based on their execution time and accuracy. The proposed model achieved an accuracy of 95.2% for multiclass classification and 99.4% for binary classification. Experimental findings indicate that our proposed model significantly outperforms existing methods; therefore, this model could be applicable to support doctors in osteosarcoma diagnosis in clinics. In addition, our proposed model is integrated into a web application using the FastAPI web framework to provide a real-time prediction.

The pathogenetic influence of smoking on SARS-CoV-2 infection: Integrative transcriptome and regulomics analysis of lung epithelial cells.

Corona virus disease (COVID-19) has been emerged as pandemic infectious disease. The recent epidemiological data suggest that the smokers are more vulnerable to infection with COVID-19; however, the influence of smoking (SMK) on the COVID-19 infected patients and the mortality is not known yet. In this study, we aimed to discern the influence of SMK on COVID-19 infected patients utilizing the transcriptomics data of COVID-19 infected lung epithelial cells and transcriptomics data smoking matched with controls from lung epithelial cells. The bioinformatics based analysis revealed the molecular insights into the level of transcriptional changes and pathways which are important to identify the impact of smoking on COVID-19 infection and prevalence. We compared differentially expressed genes (DEGs) between COVID-19 and SMK and 59 DEGs were identified as consistently dysregulated at transcriptomics levels. The correlation network analyses were constructed for these common genes using WGCNA R package to see the relationship among these genes. Integration of DEGs with network analysis (protein-protein interaction) showed the presence of 9 hub proteins as key so called "candidate hub proteins" overlapped between COVID-19 patients and SMK. The Gene Ontology and pathways analysis demonstrated the enrichment of inflammatory pathway such as IL-17 signaling pathway, Interleukin-6 signaling, TNF signaling pathway and MAPK1/MAPK3 signaling pathways that might be the therapeutic targets in COVID-19 for smoking persons. The identified genes, pathways, hubs genes, and their regulators might be considered for establishment of key genes and drug targets for SMK and COVID-19.

Systematic approach to identify therapeutic targets and functional pathways for the cervical cancer.

BACKGROUND: In today's society, cancer has become a big concern. The most common cancers in women are breast cancer (BC), endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC). CC is a type of cervix cancer that is the fourth most common cancer in women and the fourth major cause of death. RESULTS: This research uses a network approach to discover genetic connections, functional enrichment, pathways analysis, microRNAs transcription factors (miRNA-TF) co-regulatory network, gene-disease associations, and therapeutic targets for CC. Three datasets from the NCBI's GEO collection were considered for this investigation. Then, using a comparison approach between the datasets, 315 common DEGs were discovered. The PPI network was built using a variety of combinatorial statistical approaches and bioinformatics tools, and the PPI network was then utilized to identify hub genes and critical modules. CONCLUSION: Furthermore, we discovered that CC has specific similar links with the progression of different tumors using Gene Ontology terminology and pathway analysis. Transcription factors-gene linkages, gene-disease correlations, and the miRNA-TF co-regulatory network were revealed to have functional enrichments. We believe the candidate drugs identified in this study could be effective for advanced CC treatment.

PSRTTCA: A new approach for improving the prediction and characterization of tumor T cell antigens using propensity score representation learning.

Despite the arsenal of existing cancer therapies, the ongoing recurrence and new cases of cancer pose a serious health concern that necessitates the development of new and effective treatments. Cancer immunotherapy, which uses the body's immune system to combat cancer, is a promising treatment option. As a result, in silico methods for identifying and characterizing tumor T cell antigens (TTCAs) would be useful for better understanding their functional mechanisms. Although few computational methods for TTCA identification have been developed, their lack of model interpretability is a major drawback. Thus, developing computational methods for the effective identification and characterization of TTCAs is a critical endeavor. PSRTTCA, a new machine learning (ML)-based approach for improving the identification and characterization of TTCAs based on their primary sequences, is proposed in this study. Specifically, we introduce a new propensity score representation learning algorithm that allows one to generate various sets of propensity scores of amino acids, dipeptides, and g-gap dipeptides to be TTCAs. To enhance the predictive performance, optimal sets of variant propensity scores were determined and fed into the final meta-predictor (PSRTTCA). Benchmarking results revealed that PSRTTCA was a more precise and promising tool for the identification and characterization of TTCAs than conventional ML classifiers and existing methods. Furthermore, PSR-derived propensities of amino acids in becoming TTCAs are used to reveal the relationship between TTCAs and their informative physicochemical properties in order to provide insights into TTCA characteristics. Finally, a user-friendly online computational platform of PSRTTCA is publicly available at http://pmlabstack.pythonanywhere.com/PSRTTCA. The PSRTTCA predictor is anticipated to facilitate community-wide efforts in accelerating the discovery of novel TTCAs for cancer immunotherapy and other clinical applications.

Severity of COVID-19 patients with coexistence of asthma and vitamin D deficiency.

Coronavirus disease 2019 (COVID-19)-driven global pandemic triggered innumerable health complications, imposing great challenges in managing other respiratory diseases like asthma. Furthermore, increases in the underlying inflammation involved in the fatality of COVID-19 have been linked with lack of vitamin D. In this research work, we intend to investigate the possible genetic linkage of asthma and vitamin D deficiency with the severity and fatality of COVID-19 using a network-based approach. We identified and analysed 41 and 14 differentially expressed genes (DEGs) of COVID-19 being common with asthma and vitamin D deficiency, respectively, through the comparative differential gene expression analysis and their footprints on signalling pathways. Gene set enrichment analysis for GO terms and signalling pathways reveals key biological activities, including inflammatory response-related pathways (e.g., cytokine- and chemokine-mediated signalling pathways, IL-17, and TNF signalling pathways). Besides, the Protein-Protein Interaction network analysis of those DEGs reveals hub proteins, some of which are reported as inflammatory antiviral interferon-stimulated biomarkers that potentially drive the cytokine storm leading to COVID-19 severity and fatality, and contributes in the early stage of viral replication, respectively. Moreover, the regulatory network analysis found these DEGs associated with antiviral and tumour inhibitory transcription factors and micro-RNAs. Finally, drug-target enrichment analysis yields tetradioxin, estradiol, arsenenous acid, and zinc, which have been reported to be effective in suppressing the pro-inflammatory cytokines production, and other respiratory tract infections. Our results yield shared biomarker-driven key hypotheses followed by network-based analytics, demystifying the mechanistic details of COVID-19 comorbidity of asthma and vitamin D deficiency with their potential therapeutic implications.

Improved prediction and characterization of blood-brain barrier penetrating peptides using estimated propensity scores of dipeptides.

The blood-brain barrier (BBB) is the primary barrier with a highly selective semipermeable border between blood vascular endothelial cells and the central nervous system. Since BBB can prevent drugs circulating in the blood from crossing into the interstitial fluid of the brain where neurons reside, many researchers are working hard on developing drug delivery systems to penetrate the BBB which currently poses a challenge. Thus, blood-brain barrier penetrating peptides (B3PPs) are an alternative neurotherapeutic for brain-related disorder since they can facilitate drug delivery into the brain. In the meanwhile, developing computational methods that are effective for both the identification and characterization of B3PPs in a cost-effective manner plays an important role for basic reach and in the pharmaceutical industry. Even though few computational methods for B3PP identification have been developed, their performance might fail in terms of generalization ability and interpretability. In this study, a novel and efficient scoring card method-based predictor (termed SCMB3PP) is presented for improving B3PP identification and characterization. To overcome the limitation of black-box computational approaches, the SCMB3PP predictor can automatically estimate amino acid and dipeptide propensities to be B3PPs. Both cross-validation and independent tests indicate that SCMB3PP can achieve impressive performance and outperform various popular machine learning-based methods and the existing methods on multiple independent test datasets. Furthermore, SCMB3PP-derived amino acid propensities were utilized to identify informative biophysical and biochemical properties for characterizing B3PPs. Finally, an online user-friendly web server ( http://pmlabstack.pythonanywhere.com/SCMB3PP ) is established to identify novel and potential B3PP cost-effectively. This novel computational approach is anticipated to facilitate the large-scale identification of high potential B3PP candidates for follow-up experimental validation.

StackPR is a new computational approach for large-scale identification of progesterone receptor antagonists using the stacking strategy.

Progesterone receptors (PRs) are implicated in various cancers since their presence/absence can determine clinical outcomes. The overstimulation of progesterone can facilitate oncogenesis and thus, its modulation through PR inhibition is urgently needed. To address this issue, a novel stacked ensemble learning approach (termed StackPR) is presented for fast, accurate, and large-scale identification of PR antagonists using only SMILES notation without the need for 3D structural information. We employed six popular machine learning (ML) algorithms (i.e., logistic regression, partial least squares, k-nearest neighbor, support vector machine, extremely randomized trees, and random forest) coupled with twelve conventional molecular descriptors to create 72 baseline models. Then, a genetic algorithm in conjunction with the self-assessment-report approach was utilized to determine m out of the 72 baseline models as means of developing the final meta-predictor using the stacking strategy and tenfold cross-validation test. Experimental results on the independent test dataset show that StackPR achieved impressive predictive performance with an accuracy of 0.966 and Matthew's coefficient correlation of 0.925. In addition, analysis based on the SHapley Additive exPlanation algorithm and molecular docking indicates that aliphatic hydrocarbons and nitrogen-containing substructures were the most important features for having PR antagonist activity. Finally, we implemented an online webserver using StackPR, which is freely accessible at http://pmlabstack.pythonanywhere.com/StackPR . StackPR is anticipated to be a powerful computational tool for the large-scale identification of unknown PR antagonist candidates for follow-up experimental validation.

Bioinformatics Strategies to Identify Shared Molecular Biomarkers That Link Ischemic Stroke and Moyamoya Disease with Glioblastoma.

Expanding data suggest that glioblastoma is accountable for the growing prevalence of various forms of stroke formation, such as ischemic stroke and moyamoya disease. However, the underlying deterministic details are still unspecified. Bioinformatics approaches are designed to investigate the relationships between two pathogens as well as fill this study void. Glioblastoma is a form of cancer that typically occurs in the brain or spinal cord and is highly destructive. A stroke occurs when a brain region starts to lose blood circulation and prevents functioning. Moyamoya disorder is a recurrent and recurring arterial disorder of the brain. To begin, adequate gene expression datasets on glioblastoma, ischemic stroke, and moyamoya disease were gathered from various repositories. Then, the association between glioblastoma, ischemic stroke, and moyamoya was established using the existing pipelines. The framework was developed as a generalized workflow to allow for the aggregation of transcriptomic gene expression across specific tissue; Gene Ontology (GO) and biological pathway, as well as the validation of such data, are carried out using enrichment studies such as protein-protein interaction and gold benchmark databases. The results contribute to a more profound knowledge of the disease mechanisms and unveil the projected correlations among the diseases.

Early-Stage Detection of Ovarian Cancer Based on Clinical Data Using Machine Learning Approaches.

One of the common types of cancer for women is ovarian cancer. Still, at present, there are no drug therapies that can properly cure this deadly disease. However, early-stage detection could boost the life expectancy of the patients. The main aim of this work is to apply machine learning models along with statistical methods to the clinical data obtained from 349 patient individuals to conduct predictive analytics for early diagnosis. In statistical analysis, Student's t-test as well as log fold changes of two groups are used to find the significant blood biomarkers. Furthermore, a set of machine learning models including Random Forest (RF), Support Vector Machine (SVM), Decision Tree (DT), Extreme Gradient Boosting Machine (XGBoost), Logistic Regression (LR), Gradient Boosting Machine (GBM) and Light Gradient Boosting Machine (LGBM) are used to build classification models to stratify benign-vs.-malignant ovarian cancer patients. Both of the analysis techniques recognized that the serumsamples carbohydrate antigen 125, carbohydrate antigen 19-9, carcinoembryonic antigen and human epididymis protein 4 are the top-most significant biomarkers as well as neutrophil ratio, thrombocytocrit, hematocrit blood samples, alanine aminotransferase, calcium, indirect bilirubin, uric acid, natriumas as general chemistry tests. Moreover, the results from predictive analysis suggest that the machine learning models can classify malignant patients from benign patients with accuracy as good as 91%. Since generally, early-stage detection is not available, machine learning detection could play a significant role in cancer diagnosis.

NEPTUNE: A novel computational approach for accurate and large-scale identification of tumor homing peptides.

Tumor homing peptides (THPs) play a crucial role in recognizing and specifically binding to cancer cells. Although experimental approaches can facilitate the precise identification of THPs, they are usually time-consuming, labor-intensive, and not cost-effective. However, computational approaches can identify THPs by utilizing sequence information alone, thus highlighting their great potential for large-scale identification of THPs. Herein, we propose NEPTUNE, a novel computational approach for the accurate and large-scale identification of THPs from sequence information. Specifically, we constructed variant baseline models from multiple feature encoding schemes coupled with six popular machine learning algorithms. Subsequently, we comprehensively assessed and investigated the effects of these baseline models on THP prediction. Finally, the probabilistic information generated by the optimal baseline models is fed into a support vector machine-based classifier to construct the final meta-predictor (NEPTUNE). Cross-validation and independent tests demonstrated that NEPTUNE achieved superior performance for THP prediction compared with its constituent baseline models and the existing methods. Moreover, we employed the powerful SHapley additive exPlanations method to improve the interpretation of NEPTUNE and elucidate the most important features for identifying THPs. Finally, we implemented an online web server using NEPTUNE, which is available at http://pmlabstack.pythonanywhere.com/NEPTUNE. NEPTUNE could be beneficial for the large-scale identification of unknown THP candidates for follow-up experimental validation.

Discovering Common Pathophysiological Processes between COVID-19 and Cystic Fibrosis by Differential Gene Expression Pattern Analysis.

Coronaviruses are a family of viruses that infect mammals and birds. Coronaviruses cause infections of the respiratory system in humans, which can be minor or fatal. A comparative transcriptomic analysis has been performed to establish essential profiles of the gene expression of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) linked to cystic fibrosis (CF). Transcriptomic studies have been carried out in relation to SARS-CoV-2 since a number of people have been diagnosed with CF. The recognition of differentially expressed genes demonstrated 8 concordant genes shared between the SARS-CoV-2 and CF. Extensive gene ontology analysis and the discovery of pathway enrichment demonstrated SARS-CoV-2 response to CF. The gene ontological terms and pathway enrichment mechanisms derived from this research may affect the production of successful drugs, especially for the people with the following disorder. Identification of TF-miRNA association network reveals the interconnection between TF genes and miRNAs, which may be effective to reveal the other influenced disease that occurs for SARS-CoV-2 to CF. The enrichment of pathways reveals SARS-CoV-2-associated CF mostly engaged with the type of innate immune system, Toll-like receptor signaling pathway, pantothenate and CoA biosynthesis, allograft rejection, graft-versus-host disease, intestinal immune network for IgA production, mineral absorption, autoimmune thyroid disease, legionellosis, viral myocarditis, inflammatory bowel disease (IBD), etc. The drug compound identification demonstrates that the drug targets of IMIQUIMOD and raloxifene are the most significant with the significant hub DEGs.

AMYPred-FRL is a novel approach for accurate prediction of amyloid proteins by using feature representation learning.

Amyloid proteins have the ability to form insoluble fibril aggregates that have important pathogenic effects in many tissues. Such amyloidoses are prominently associated with common diseases such as type 2 diabetes, Alzheimer's disease, and Parkinson's disease. There are many types of amyloid proteins, and some proteins that form amyloid aggregates when in a misfolded state. It is difficult to identify such amyloid proteins and their pathogenic properties, but a new and effective approach is by developing effective bioinformatics tools. While several machine learning (ML)-based models for in silico identification of amyloid proteins have been proposed, their predictive performance is limited. In this study, we present AMYPred-FRL, a novel meta-predictor that uses a feature representation learning approach to achieve more accurate amyloid protein identification. AMYPred-FRL combined six well-known ML algorithms (extremely randomized tree, extreme gradient boosting, k-nearest neighbor, logistic regression, random forest, and support vector machine) with ten different sequence-based feature descriptors to generate 60 probabilistic features (PFs), as opposed to state-of-the-art methods developed by a single feature-based approach. A logistic regression recursive feature elimination (LR-RFE) method was used to find the optimal m number of 60 PFs in order to improve the predictive performance. Finally, using the meta-predictor approach, the 20 selected PFs were fed into a logistic regression method to create the final hybrid model (AMYPred-FRL). Both cross-validation and independent tests showed that AMYPred-FRL achieved superior predictive performance than its constituent baseline models. In an extensive independent test, AMYPred-FRL outperformed the existing methods by 5.5% and 16.1%, respectively, with accuracy and MCC of 0.873 and 0.710. To expedite high-throughput prediction, a user-friendly web server of AMYPred-FRL is freely available at http://pmlabstack.pythonanywhere.com/AMYPred-FRL . It is anticipated that AMYPred-FRL will be a useful tool in helping researchers to identify new amyloid proteins.

A classification of MRI brain tumor based on two stage feature level ensemble of deep CNN models.

The brain tumor is one of the deadliest cancerous diseases and its severity has turned it to the leading cause of cancer related mortality. The treatment procedure of the brain tumor depends on the type, location and size of the tumor. Relying solely on human inspection for precise categorization can lead to inevitably dangerous situation. This manual diagnosis process can be improved and accelerated through an automated Computer Aided Diagnosis (CADx) system. In this article, a novel approach using two-stage feature ensemble of deep Convolutional Neural Networks (CNN) is proposed for precise and automatic classification of brain tumors. Three unique Magnetic Resonance Imaging (MRI) datasets and a dataset merging all the unique datasets are considered. The datasets contain three types of brain tumor (meningioma, glioma, pituitary) and normal brain images. From five pre-trained models and a proposed CNN model, the best models are chosen and concatenated in two stages for feature extraction. The best classifier is also chosen among five different classifiers based on accuracy. From the extracted features, most substantial features are selected using Principal Component Analysis (PCA) and fed into the classifier. The robustness of the proposed two stage ensemble model is analyzed using several performance metrics and three different experiments. Through the prominent performance, the proposed model is able to outperform other existing models attaining an average accuracy of 99.13% by optimization of the developed algorithms. Here, the individual accuracy for Dataset 1, Dataset 2, Dataset 3, and Merged Dataset is 99.67%, 98.16%, 99.76%, and 98.96% respectively. Finally a User Interface (UI) is created using the proposed model for real time validation.

Network based systems biology approach to identify diseasome and comorbidity associations of Systemic Sclerosis with cancers.

Systemic Sclerosis (SSc) is an autoimmune disease associated with changes in the skin's structure in which the immune system attacks the body. A recent meta-analysis has reported a high incidence of cancer prognosis including lung cancer (LC), leukemia (LK), and lymphoma (LP) in patients with SSc as comorbidity but its underlying mechanistic details are yet to be revealed. To address this research gap, bioinformatics methodologies were developed to explore the comorbidity interactions between a pair of diseases. Firstly, appropriate gene expression datasets from different repositories on SSc and its comorbidities were collected. Then the interconnection between SSc and its cancer comorbidities was identified by applying the developed pipelines. The pipeline was designed as a generic workflow to demonstrate a premise comorbid condition that integrate regarding gene expression data, tissue/organ meta-data, Gene Ontology (GO), Molecular pathways, and other online resources, and analyze them with Gene Set Enrichment Analysis (GSEA), Pathway enrichment and Semantic Similarity (SS). The pipeline was implemented in R and can be accessed through our Github repository: https://github.com/hiddenntreasure/comorbidity. Our result suggests that SSc and its cancer comorbidities share differentially expressed genes, functional terms (gene ontology), and pathways. The findings have led to a better understanding of disease pathways and our developed methodologies may be applied to any set of diseases for finding any association between them. This research may be used by physicians, researchers, biologists, and others.

Identification of Potential Key Genes and Molecular Mechanisms of Medulloblastoma Based on Integrated Bioinformatics Approach.

BACKGROUND: Medulloblastoma (MB) is the most occurring brain cancer that mostly happens in childhood age. This cancer starts in the cerebellum part of the brain. This study is designed to screen novel and significant biomarkers, which may perform as potential prognostic biomarkers and therapeutic targets in MB. METHODS: A total of 103 MB-related samples from three gene expression profiles of GSE22139, GSE37418, and GSE86574 were downloaded from the Gene Expression Omnibus (GEO). Applying the limma package, all three datasets were analyzed, and 1065 mutual DEGs were identified including 408 overexpressed and 657 underexpressed with the minimum cut-off criteria of ∣log fold change | >1 and P < 0.05. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways enrichment analyses were executed to discover the internal functions of the mutual DEGs. The outcomes of enrichment analysis showed that the common DEGs were significantly connected with MB progression and development. The Search Tool for Retrieval of Interacting Genes (STRING) database was used to construct the interaction network, and the network was displayed using the Cytoscape tool and applying connectivity and stress value methods of cytoHubba plugin 35 hub genes were identified from the whole network. RESULTS: Four key clusters were identified using the PEWCC 1.0 method. Additionally, the survival analysis of hub genes was brought out based on clinical information of 612 MB patients. This bioinformatics analysis may help to define the pathogenesis and originate new treatments for MB.

SCMTHP: A New Approach for Identifying and Characterizing of Tumor-Homing Peptides Using Estimated Propensity Scores of Amino Acids.

Tumor-homing peptides (THPs) are small peptides that can recognize and bind cancer cells specifically. To gain a better understanding of THPs' functional mechanisms, the accurate identification and characterization of THPs is required. Although some computational methods for in silico THP identification have been proposed, a major drawback is their lack of model interpretability. In this study, we propose a new, simple and easily interpretable computational approach (called SCMTHP) for identifying and analyzing tumor-homing activities of peptides via the use of a scoring card method (SCM). To improve the predictability and interpretability of our predictor, we generated propensity scores of 20 amino acids as THPs. Finally, informative physicochemical properties were used for providing insights on characteristics giving rise to the bioactivity of THPs via the use of SCMTHP-derived propensity scores. Benchmarking experiments from independent test indicated that SCMTHP could achieve comparable performance to state-of-the-art method with accuracies of 0.827 and 0.798, respectively, when evaluated on two benchmark datasets consisting of Main and Small datasets. Furthermore, SCMTHP was found to outperform several well-known machine learning-based classifiers (e.g., decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes and partial least squares regression) as indicated by both 10-fold cross-validation and independent tests. Finally, the SCMTHP web server was established and made freely available online. SCMTHP is expected to be a useful tool for rapid and accurate identification of THPs and for providing better understanding on THP biophysical and biochemical properties.

Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU).

Background: Previous studies have revealed the role of dysregulated urokinase plasminogen activator (encoded by PLAU) expression and activity in several pathways associated with cancer progression. However, systematic investigation into the association of PLAU expression with factors that modulate PDAC (pancreatic ductal adenocarcinoma) progression is lacking, such as those affecting stromal (pancreatic stellate cell, PSC)-cancer cell interactions, tumour immunity, PDAC subtypes and clinical outcomes from potential PLAU inhibition. Methods: This study used an integrated bioinformatics approach to identify prognostic markers correlated with PLAU expression using different transcriptomics, proteomics, and clinical data sets. We then determined the association of dysregulated PLAU and correlated signatures with oncogenic pathways, metastatic phenotypes, stroma, immunosuppressive tumour microenvironment (TME) and clinical outcome. Finally, using an in vivo orthotopic model of pancreatic cancer, we confirmed the predicted effect of inhibiting PLAU on tumour growth and metastasis. Results: Our analyses revealed that PLAU upregulation is not only associated with numerous other prognostic markers but also associated with the activation of various oncogenic signalling pathways, aggressive phenotypes relevant to PDAC growth and metastasis, such as proliferation, epithelial-mesenchymal transition (EMT), stemness, hypoxia, extracellular cell matrix (ECM) degradation, upregulation of stromal signatures, and immune suppression in the tumour microenvironment (TME). Moreover, the upregulation of PLAU was directly connected with signalling pathways known to mediate PSC-cancer cell interactions. Furthermore, PLAU upregulation was associated with the aggressive basal/squamous phenotype of PDAC and significantly reduced overall survival, indicating that this subset of patients may benefit from therapeutic interventions to inhibit PLAU activity. Our studies with a clinically relevant orthotopic pancreatic model showed that even short-term PLAU inhibition is sufficient to significantly halt tumour growth and, importantly, eliminate visible metastasis. Conclusion: Elevated PLAU correlates with increased aggressive phenotypes, stromal score, and immune suppression in PDAC. PLAU upregulation is also closely associated with the basal subtype type of PDAC; patients with this subtype are at high risk of mortality from the disease and may benefit from therapeutic targeting of PLAU.