The heart is an essential organ in the human body. It contains various types of cells, such as cardiomyocytes, mesothelial cells, endothelial cells, and fibroblasts. The interactions between these cells determine the vital functions of the heart. Therefore, identifying the different cell types and revealing the expression rules in these cell types are crucial. In this study, multiple machine learning methods were used to analyze the heart single-cell profiles with 11 different heart cell types. The single-cell profiles were first analyzed via light gradient boosting machine method to evaluate the importance of gene features on the profiling dataset, and a ranking feature list was produced. This feature list was then brought into the incremental feature selection method to identify the best features and build the optimal classifiers. The results suggested that the best decision tree (DT) and random forest classification models achieved the highest weighted F1 scores of 0.957 and 0.981, respectively. The selected features, such as NPPA, LAMA2, DLC1, and the classification rules extracted from the optimal DT classifier played a crucial role in cardiac structure and function in recent research and enrichment analysis. In particular, some lncRNAs (LINC02019, NEAT1) were found to be quite important for the recognition of different cardiac cell types. In summary, these findings provide a solid academic foundation for the development of molecular diagnostics and biomarker discovery for cardiac diseases.
22 December 2023 in Computers in Biology and Medicine
SARS-CoV-2 shows great evolutionary capacity through a high frequency of genomic variation during transmission. Evolved SARS-CoV-2 often demonstrates resistance to previous vaccines and can cause poor clinical status in patients. Mutations in the SARS-CoV-2 genome involve mutations in structural and nonstructural proteins, and some of these proteins such as spike proteins have been shown to be directly associated with the clinical status of patients with severe COVID-19 pneumonia. In this study, we collected genome-wide mutation information of virulent strains and the severity of COVID-19 pneumonia in patients varying depending on their clinical status. Important protein mutations and untranslated region mutations were extracted using machine learning methods. First, through Boruta and four ranking algorithms (least absolute shrinkage and selection operator, light gradient boosting machine, max-relevance and min-redundancy, and Monte Carlo feature selection), mutations that were highly correlated with the clinical status of the patients were screened out and sorted in four feature lists. Some mutations such as D614G and V1176F were shown to be associated with viral infectivity. Moreover, previously unreported mutations such as A320V of nsp14 and I164ILV of nsp14 were also identified, which suggests their potential roles. We then applied the incremental feature selection method to each feature list to construct efficient classifiers, which can be directly used to distinguish the clinical status of COVID-19 patients. Meanwhile, four sets of quantitative rules were set up, which can help us to more intuitively understand the role of each mutation in differentiating the clinical status of COVID-19 patients. Identified key mutations linked to virologic properties will help better understand the mechanisms of infection and will aid in the development of antiviral treatments.
Atopic dermatitis and psoriasis are members of a family of inflammatory skin disorders. Cellular immune responses in skin tissues contribute to the development of these diseases. However, their underlying immune mechanisms remain to be fully elucidated. We developed a computational pipeline for analyzing the single-cell RNA-sequencing profiles of the Human Cell Atlas skin dataset to investigate the pathological mechanisms of skin diseases. First, we applied the maximum relevance criterion and the Boruta feature selection method to exclude irrelevant gene features from the single-cell gene expression profiles of inflammatory skin disease samples and healthy controls. The retained gene features were ranked by using the Monte Carlo feature selection method on the basis of their importance, and a feature list was compiled. This list was then introduced into the incremental feature selection method that combined the decision tree and random forest algorithms to extract important cell markers and thus build excellent classifiers and decision rules. These cell markers and their expression patterns have been analyzed and validated in recent studies and are potential therapeutic and diagnostic targets for skin diseases because their expression affects the pathogenesis of inflammatory skin diseases.
21 December 2023 in Medical & Biological Engineering & Computing
The rapid spread of COVID-19 has become a major concern for people’s lives and health all around the world. COVID-19 patients in various phases and severity require individualized treatment given that different patients may develop different symptoms. We employed machine learning methods to discover biomarkers that may accurately classify COVID-19 in various disease states and severities in this study. The blood gene expression profiles from 50 COVID-19 patients without intensive care, 50 COVID-19 patients with intensive care, 10 non-COVID-19 individuals without intensive care, and 16 non-COVID-19 individuals with intensive care were analyzed. Boruta was first used to remove irrelevant gene features in the expression profiles, and then, the minimum redundancy maximum relevance was applied to sort the remaining features. The generated feature-ranked list was fed into the incremental feature selection method to discover the essential genes and build powerful classifiers. The molecular mechanism of some biomarker genes was addressed using recent studies, and biological functions enriched by essential genes were examined. Our findings imply that genes including UBE2C, PCLAF, CDK1, CCNB1, MND1, APOBEC3G, TRAF3IP3, CD48, and GZMA play key roles in defining the different states and severity of COVID-19. Thus, a new point of reference is provided for understanding the disease’s etiology and facilitating a precise therapy.