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Identifying COVID-19-Specific Transcriptomic Biomarkers with Machine Learning Methods.

ABSTRACT: COVID-19, a severe respiratory disease caused by a new type of coronavirus SARS-CoV-2, has been spreading all over the world. Patients infected with SARS-CoV-2 may have no pathogenic symptoms, i.e., presymptomatic patients and asymptomatic patients. Both patients could further spread the virus to other susceptible people, thereby making the control of COVID-19 difficult. The two major challenges for COVID-19 diagnosis at present are as follows: (1) patients could share similar symptoms with other respiratory infections, and (2) patients may not have any symptoms but could still spread the virus. Therefore, new biomarkers at different omics levels are required for the large-scale screening and diagnosis of COVID-19. Although some initial analyses could identify a group of candidate gene biomarkers for COVID-19, the previous work still could not identify biomarkers capable for clinical use in COVID-19, which requires disease-specific diagnosis compared with other multiple infectious diseases. As an extension of the previous study, optimized machine learning models were applied in the present study to identify some specific qualitative host biomarkers associated with COVID-19 infection on the basis of a publicly released transcriptomic dataset, which included healthy controls and patients with bacterial infection, influenza, COVID-19, and other kinds of coronavirus. This dataset was first analysed by Boruta, Max-Relevance and Min-Redundancy feature selection methods one by one, resulting in a feature list. This list was fed into the incremental feature selection method, incorporating one of the classification algorithms to extract essential biomarkers and build efficient classifiers and classification rules. The capacity of these findings to distinguish COVID-19 with other similar respiratory infectious diseases at the transcriptomic level was also validated, which may improve the efficacy and accuracy of COVID-19 diagnosis.

SUBMITTER: Chen L

PROVIDER: S-EPMC8272456 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Individuals with the SARS-CoV-2 infection may experience a wide range of symptoms, from being asymptomatic to having a mild fever and cough to a severe respiratory impairment that results in death. MicroRNA (miRNA), which plays a role in the antiviral effects of SARS-CoV-2 infection, has the potential to be used as a novel marker to distinguish between patients who have various COVID-19 clinical severities. In the current study, the existing blood expression profiles reported in two previous studies were combined for deep analyses. The final profiles contained 1444 miRNAs in 375 patients from six categories, which were as follows: 30 patients with mild COVID-19 symptoms, 81 patients with moderate COVID-19 symptoms, 30 non-COVID-19 patients with mild symptoms, 137 patients with severe COVID-19 symptoms, 31 non-COVID-19 patients with severe symptoms, and 66 healthy controls. An efficient computational framework containing four feature selection methods (LASSO, LightGBM, MCFS, and mRMR) and four classification algorithms (DT, KNN, RF, and SVM) was designed to screen clinical miRNA markers, and a high-precision RF model with a 0.780 weighted F1 was constructed. Some miRNAs, including miR-24-3p, whose differential expression was discovered in patients with acute lung injury complications brought on by severe COVID-19, and miR-148a-3p, differentially expressed against SARS-CoV-2 structural proteins, were identified, thereby suggesting the effectiveness and accuracy of our framework. Meanwhile, we extracted classification rules based on the DT model for the quantitative representation of the role of miRNA expression in differentiating COVID-19 patients with different severities. The search for novel biomarkers that could predict the severity of the disease could aid in the clinical diagnosis of COVID-19 and in exploring the specific mechanisms of the complications caused by SARS-CoV-2 infection. Moreover, new therapeutic targets for the disease may be found.

Project description:Background: Microglia plays complex and crucial roles in multiple sclerosis (MS). This study aimed to explore the biological significance of microglia-associated genes in experimental autoimmune encephalomyelitis (EAE) . Methods: Differentially expressed genes (DEGs) were screened with six machine learning (ML) methods, which were also utilized to validate the microglia-associated DEGs in three public databases. ceRNA and Protein–protein interaction (PPI) network analyses were utilized to identify the interaction of the 6 novel biomarkers with other molecules. Then, CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were employed to quantify the relative abundance of each immune cell infiltration, respectively. qRT-PCR was performed to test the expression of key DEGs in murine models. Results: A total of 247 DEmRNA, 499 DElncRNAs and 269 DEcircRNAs were identified. With screening strategy of five ML algorithms, 6 DEmRNAs were obtained including NGP, HIST1H2BJ, PBLD1, MBLN3, CD180 and F10. Then the 6 DEmRNAs were used as a multigene signature to construct models to differentiate EAE from normal microglia, and AUC value for each model was greater than 0.8. The diagnostic value of these 6 DEmRNAs were identified and further verified by qRT-PCR. Then, differential expression for five out of these 6 DEmRNAs, namely NGP, HIST1H2BJ, PBLD1, MBLN3, and F10 were confirmed. Using PPI analysis, DEmRNAs frequently interacting with transcription factors (TFs), potential drugs and RBPs were identified. With immune cell infiltration analyses, we found EAE microglia presented high levels of immune infiltration, especially Nature Killer (NK) cells and CD8+ T cells. We also reported circRNA (circRNA_00638) was predicted to bind to 76 RBPs. Conclusions: We identified and validated 6 novel microglia related genes and developed a multigene signature with ML methods to confirm their ability to accurately diagnose and characterize biological alterations in EAE microglia. The six key DEmRNAs might also be latent targets for immunoregulatory therapy.

Project description:BackgroundResearch gaps refer to unanswered questions in the existing body of knowledge, either due to a lack of studies or inconclusive results. Research gaps are essential starting points and motivation in scientific research. Traditional methods for identifying research gaps, such as literature reviews and expert opinions, can be time consuming, labor intensive, and prone to bias. They may also fall short when dealing with rapidly evolving or time-sensitive subjects. Thus, innovative scalable approaches are needed to identify research gaps, systematically assess the literature, and prioritize areas for further study in the topic of interest.ObjectiveIn this paper, we propose a machine learning-based approach for identifying research gaps through the analysis of scientific literature. We used the COVID-19 pandemic as a case study.MethodsWe conducted an analysis to identify research gaps in COVID-19 literature using the COVID-19 Open Research (CORD-19) data set, which comprises 1,121,433 papers related to the COVID-19 pandemic. Our approach is based on the BERTopic topic modeling technique, which leverages transformers and class-based term frequency-inverse document frequency to create dense clusters allowing for easily interpretable topics. Our BERTopic-based approach involves 3 stages: embedding documents, clustering documents (dimension reduction and clustering), and representing topics (generating candidates and maximizing candidate relevance).ResultsAfter applying the study selection criteria, we included 33,206 abstracts in the analysis of this study. The final list of research gaps identified 21 different areas, which were grouped into 6 principal topics. These topics were: "virus of COVID-19," "risk factors of COVID-19," "prevention of COVID-19," "treatment of COVID-19," "health care delivery during COVID-19," "and impact of COVID-19." The most prominent topic, observed in over half of the analyzed studies, was "the impact of COVID-19."ConclusionsThe proposed machine learning-based approach has the potential to identify research gaps in scientific literature. This study is not intended to replace individual literature research within a selected topic. Instead, it can serve as a guide to formulate precise literature search queries in specific areas associated with research questions that previous publications have earmarked for future exploration. Future research should leverage an up-to-date list of studies that are retrieved from the most common databases in the target area. When feasible, full texts or, at minimum, discussion sections should be analyzed rather than limiting their analysis to abstracts. Furthermore, future studies could evaluate more efficient modeling algorithms, especially those combining topic modeling with statistical uncertainty quantification, such as conformal prediction.

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Identifying COVID-19-Specific Transcriptomic Biomarkers with Machine Learning Methods.

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