Identification and evaluation of candidate COVID-19 critical genes and medicinal drugs related to plasma cells.

The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, represents one of the most significant global health crises in recent history. Despite extensive research into the immune mechanisms and therapeutic options for COVID-19, there remains a paucity of studies focusing on plasma cells. In this study, we utilized the DESeq2 package to identify differentially expressed genes (DEGs) between COVID-19 patients and controls using datasets GSE157103 and GSE152641. We employed the xCell algorithm to perform immune infiltration analyses, revealing notably elevated levels of plasma cells in COVID-19 patients compared to healthy individuals. Subsequently, we applied the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm to identify COVID-19 related plasma cell module genes. Further, positive cluster biomarker genes for plasma cells were extracted from single-cell RNA sequencing data (GSE171524), leading to the identification of 122 shared genes implicated in critical biological processes such as cell cycle regulation and viral infection pathways. We constructed a robust protein-protein interaction (PPI) network comprising 89 genes using Cytoscape, and identified 20 hub genes through cytoHubba. These genes were validated in external datasets (GSE152418 and GSE179627). Additionally, we identified three potential small molecules (GSK-1070916, BRD-K89997465, and idarubicin) that target key hub genes in the network, suggesting a novel therapeutic approach. These compounds were characterized by their ability to down-regulate AURKB, KIF11, and TOP2A effectively, as evidenced by their low free binding energies determined through computational analyses using cMAP and AutoDock. This study marks the first comprehensive exploration of plasma cells' role in COVID-19, offering new insights and potential therapeutic targets. It underscores the importance of a systematic approach to understanding and treating COVID-19, expanding the current body of knowledge and providing a foundation for future research.

Uncovering the ceRNA Network Related to the Prognosis of Stomach Adenocarcinoma Among 898 Patient Samples.

Stomach adenocarcinoma (STAD) patients are often associated with significantly high mortality rates and poor prognoses worldwide. Among STAD patients, competing endogenous RNAs (ceRNAs) play key roles in regulating one another at the post-transcriptional stage by competing for shared miRNAs. In this study, we aimed to elucidate the roles of lncRNAs in the ceRNA network of STAD, uncovering the molecular biomarkers for target therapy and prognosis. Specifically, a multitude of differentially expressed lncRNAs, miRNAs, and mRNAs (i.e., 898 samples in total) was collected and processed from TCGA. Cytoplasmic lncRNAs were kept for evaluating overall survival (OS) time and constructing the ceRNA network. Differentially expressed mRNAs in the ceRNA network were also investigated for functional and pathological insights. Interestingly, we identified one ceRNA network including 13 lncRNAs, 25 miRNAs, and 9 mRNAs. Among them, 13 RNAs were found related to the patient survival time; their individual risk score can be adopted for prognosis inference. Finally, we constructed a comprehensive ceRNA regulatory network for STAD and developed our own risk-scoring system that can predict the OS time of STAD patients by taking into account the above.

Construction of Immune Infiltration-Related LncRNA Signatures Based on Machine Learning for the Prognosis in Colon Cancer.

Colon cancer is one of the malignant tumors with high morbidity, lethality, and prevalence across global human health. Molecular biomarkers play key roles in its prognosis. In particular, immune-related lncRNAs (IRL) have attracted enormous interest in diagnosis and treatment, but less is known about their potential functions. We aimed to investigate dysfunctional IRL and construct a risk model for improving the outcomes of patients. Nineteen immune cell types were collected for identifying house-keeping lncRNAs (HKLncRNA). GSE39582 and TCGA-COAD were treated as the discovery and validation datasets, respectively. Four machine learning algorithms (LASSO, Random Forest, Boruta, and Xgboost) and a Gaussian mixture model were utilized to mine the optimal combination of lncRNAs. Univariate and multivariate Cox regression was utilized to construct the risk score model. We distinguished the functional difference in an immune perspective between low- and high-risk cohorts calculated by this scoring system. Finally, we provided a nomogram. By leveraging the microarray, sequencing, and clinical data for immune cells and colon cancer patients, we identified the 221 HKLncRNAs with a low cell type-specificity index. Eighty-seven lncRNAs were up-regulated in the immune compared to cancer cells. Twelve lncRNAs were beneficial in improving performance. A risk score model with three lncRNAs (CYB561D2, LINC00638, and DANCR) was proposed with robust ROC performance on an independent dataset. According to immune-related analysis, the risk score is strongly associated with the tumor immune microenvironment. Our results emphasized IRL has the potential to be a powerful and effective therapy for enhancing the prognostic of colon cancer.

Machine learning in metastatic cancer research: Potentials, possibilities, and prospects.

Cancer has received extensive recognition for its high mortality rate, with metastatic cancer being the top cause of cancer-related deaths. Metastatic cancer involves the spread of the primary tumor to other body organs. As much as the early detection of cancer is essential, the timely detection of metastasis, the identification of biomarkers, and treatment choice are valuable for improving the quality of life for metastatic cancer patients. This study reviews the existing studies on classical machine learning (ML) and deep learning (DL) in metastatic cancer research. Since the majority of metastatic cancer research data are collected in the formats of PET/CT and MRI image data, deep learning techniques are heavily involved. However, its black-box nature and expensive computational cost are notable concerns. Furthermore, existing models could be overestimated for their generality due to the non-diverse population in clinical trial datasets. Therefore, research gaps are itemized; follow-up studies should be carried out on metastatic cancer using machine learning and deep learning tools with data in a symmetric manner.

The comprehensive and systematic identification of BLCA-specific SF-regulated, survival-related AS events.

Bladder urothelial carcinoma (BLCA) is a complex disease with high morbidity and mortality. Changes in alternative splicing (AS) and splicing factor (SF) can affect gene expression, thus playing an essential role in tumorigenesis. This study downloaded 412 patients' clinical information and 433 samples of transcriptome profiling data from TCGA. And we collected 48 AS signatures from SpliceSeq. LASSO and Cox analyses were used for identifying survival-related AS events in BLCA. Finally, 1,645 OS-related AS events in 1,129 genes were validated by Kaplan-Meier (KM) survival analysis, ROC analysis, risk curve analysis, and independent prognostic analysis. Finally, our survey provides an AS-SF regulation network consisting of five SFs and 46 AS events. In the end, we profiled genes that AS occurred in pan-cancer and five SFs' expression in tumor and normal samples in BLCA. We selected CLIP-seq data for validation the interaction regulated by RBP. Our study paves the way for potential therapeutic targets of BLCA.

Particle Swarm Optimized Gaussian Process Classifier for Treatment Discontinuation Prediction in Multicohort Metastatic Castration-Resistant Prostate Cancer Patients.

Prostate cancer is the second leading cancer in men, according to the WHO world cancer report. Its prevention and treatment demand proper attention. Despite numerous attempts for disease prevention, prostate tumours can still become metastatic by blood circulation to other organs. Several treatments have been adopted. However, findings show that the docetaxel treatment induces adverse reactions in patients. Particle Swarm Optimized Gaussian Process Classifier (PSO-GPC) is proposed to determine when to discontinue treatment. Based on three cohorts of prostate cancer patients, we propose and compare several classifiers for the best performance in determining treatment discontinuation. Given the data skewness and class imbalance, the models are evaluated based on both the area under receiver operating characteristics curve (AUC) and area under precision recall curve (AUPRC). With the AUCs ranging between 0.6717-0.8499, and AUPRCs ranging between 0.1392-0.5423, PSO-GPC performs better than the state-of-the-art. We have carried out statistical analysis for ranking methods and analyzed independent cohort data with PSO-GPC, demonstrating its unbiased performance. A proper determination of treatment discontinuation in metastatic castration-resistant prostate cancer patients will reduce the mortality rate in cancer patients.

Machine Learning Protocols in Early Cancer Detection Based on Liquid Biopsy: A Survey.

With the advances of liquid biopsy technology, there is increasing evidence that body fluid such as blood, urine, and saliva could harbor the potential biomarkers associated with tumor origin. Traditional correlation analysis methods are no longer sufficient to capture the high-resolution complex relationships between biomarkers and cancer subtype heterogeneity. To address the challenge, researchers proposed machine learning techniques with liquid biopsy data to explore the essence of tumor origin together. In this survey, we review the machine learning protocols and provide corresponding code demos for the approaches mentioned. We discuss algorithmic principles and frameworks extensively developed to reveal cancer mechanisms and consider the future prospects in biomarker exploration and cancer diagnostics.

Protocol for Epistasis Detection with Machine Learning Using GenEpi Package.

To develop medical treatments and prevention, the association between disease and genetic variants needs to be identified. The main goal of genome-wide association study (GWAS) is to discover the underlying reason for vulnerability to disease and utilize this knowledge for the development of prevention and treatment against these diseases. Given the methods available to address the scientific problems involved in the search for epistasis, there is not any standard for detecting epistasis, and this remains a problem due to limited statistical power. The GenEpi package is a Python package that uses a two-level workflow machine learning model to detect within-gene and cross-gene epistasis. This protocol chapter shows the usage of GenEpi with example data. The package uses a three-step procedure to reduce dimensionality, select the within-gene epistasis, and select the cross-gene epistasis. The package also provides a medium to build prediction models with the combination of genetic features and environmental influences.

Ensemble learning method for the prediction of new bioactive molecules.

Pharmacologically active molecules can provide remedies for a range of different illnesses and infections. Therefore, the search for such bioactive molecules has been an enduring mission. As such, there is a need to employ a more suitable, reliable, and robust classification method for enhancing the prediction of the existence of new bioactive molecules. In this paper, we adopt a recently developed combination of different boosting methods (Adaboost) for the prediction of new bioactive molecules. We conducted the research experiments utilizing the widely used MDL Drug Data Report (MDDR) database. The proposed boosting method generated better results than other machine learning methods. This finding suggests that the method is suitable for inclusion among the in silico tools for use in cheminformatics, computational chemistry and molecular biology.