Xianchao Zhou

Gastric adenocarcinoma is a significant global health concern. Among the myriad histologic classification methods for this cancer, the Lauren classification stands out as a pivotal tool. Nonetheless, the precision and detail of current histological staging techniques frequently face scrutiny. Utilizing high-resolution single-cell transcriptomic data, this research delves into the distinctive gene expression patterns in diffuse, intestinal, and mixed gastric cancers by deploying various machine learning algorithms. The main goal was to recognize important gene markers and establish efficient classification models. The data was derived from the tumor microenvironment, with cells categorized into six groups according to two locations: tumoral and normal, and three histology types: diffuse, intestinal, and mixed. Every cell describes the expression level of 56,265 genes. We integrated seven feature selection algorithms and four classification algorithms, which increased the accuracy of classification. Importantly, our approach detected intricate expression patterns realized for the first time—for example, high expression of CLDN4 in intestinal-type gastric cancers and CCL4 and CXCR4 in diffuse-type gastric cancers. The identified gene markers and gene expression patterns provide insights into subtype-specific molecular characteristics of gastric cancer. These candidate markers may serve as a foundation for future studies aimed at validating their utility in subtype classification and clinical stratification.

Protein solubility is a critical parameter that determines the stability, activity, and functionality of proteins, with broad and far-reaching implications in biotechnology and biochemistry. Accurate prediction and control of protein solubility are essential for successful protein expression and purification in research and industrial settings. This study gathered information on soluble and insoluble proteins. In characterizing the proteins, they were mapped to STRING and characterized by functional and structural features. All functional/structural features were integrated to create a 5768-dimensional binary vector to encode proteins. Seven feature-ranking algorithms were employed to analyze the functional/structural features, yielding seven feature lists. These lists were subjected to the incremental feature selection, incorporating four classification algorithms, one by one to build effective classification models and identify functional/structural features with classification-related importance. Some essential functional/structural features used to differentiate between soluble and insoluble proteins were identified, including GO:0009987 (intercellular communication) and GO:0022613 (ribonucleoprotein complex biogenesis). The best classification model using support vector machine as the classification algorithm and 295 optimized functional/structural features generated the F1 score of 0.825, which can be a powerful tool to differentiate soluble proteins from insoluble proteins.

Post-acute sequelae of COVID-19 (PASC) is a persistent complication of severe acute respiratory syndrome coronavirus 2 infection that includes symptoms, such as fatigue, cognitive impairment, and respiratory distress. These symptoms severely affect the quality of life of patients after their recovery from COVID-19. In this study, a group of machine learning algorithms analyzed the whole blood RNA-seq data from patients with different PASC levels. The purpose of this analysis was to identify the gene markers associated with PASC and the special expression patterns for different PASC levels. By comparing the quality of life of patients after the acute phase of COVID-19 and before the disease, samples in the dataset were divided into three groups, namely, “Better,” “The Same,” and “Worse.” Each patient was represented by the expression levels of 58,929 genes. The machine learning-based workflow included six feature-ranking algorithms, incremental feature selection (IFS), and four classification algorithms. The feature ranking algorithms were in charge of assessing feature importance, whereas IFS with classification algorithms were used to extract essential genes and to construct efficient classifiers and classification rules. The expression of top genes in the results was associated with the immune response to viral infection, which is supported by the published literature. For example, patients with low CCDC18 expression and high CPED1 expression had good quality of life, whereas those with low CDC16 expression had poor quality of life. Graphical Abstract

As COVID-19 develops, dynamic changes occur in the patient’s immune system. Changes in molecular levels in different immune cells can reflect the course of COVID-19. This study aims to uncover the molecular characteristics of different immune cell subpopulations at different stages of COVID-19. We designed a machine learning workflow to analyze scRNA-seq data of three immune cell types (B, T, and myeloid cells) in four levels of COVID-19 severity/outcome. The datasets for three cell types included 403,700 B-cell, 634,595 T-cell, and 346,547 myeloid cell samples. Each cell subtype was divided into four groups, control, convalescence, progression mild/moderate, and progression severe/critical, and each immune cell contained 27,943 gene features. A feature analysis procedure was applied to the data of each cell type. Irrelevant features were first excluded according to their relevance to the target variable measured by mutual information. Then, four ranking algorithms (last absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, and max-relevance and min-redundancy) were adopted to analyze the remaining features, resulting in four feature lists. These lists were fed into the incremental feature selection, incorporating three classification algorithms (decision tree, k-nearest neighbor, and random forest) to extract key gene features and construct classifiers with superior performance. The results confirmed that genes such as PFN1, RPS26, and FTH1 played important roles in SARS-CoV-2 infection. These findings provide a useful reference for the understanding of the ongoing effect of COVID-19 development on the immune system.

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.

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.

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.