High-dimensional Gene Expression Data Research Articles

Fast Variational Inference for Bayesian Factor Analysis in Single and Multi-Study Settings

Factors models are commonly used to analyze high-dimensional data in both single-study and multi-study settings. Bayesian inference for such models relies on Markov chain Monte Carlo (MCMC) methods, which scale poorly as the number of studies, observations, or measured variables increase. To address this issue, we propose new variational inference algorithms to approximate the posterior distribution of Bayesian latent factor models using the multiplicative gamma process shrinkage prior. The proposed algorithms provide fast approximate inference at a fraction of the time and memory of MCMC-based implementations while maintaining comparable accuracy in characterizing the data covariance matrix. We conduct extensive simulations to evaluate our proposed algorithms and show their utility in estimating the model for high-dimensional multi-study gene expression data in ovarian cancers. Overall, our proposed approaches enable more efficient and scalable inference for factor models, facilitating their use in high-dimensional settings. An R package VIMSFA implementing our methods is available on GitHub (github.com/blhansen/VI-MSFA). Supplementary materials for this article are available online.

Improved aquila optimizer with mRMR for feature selection of high-dimensional gene expression data

Improved aquila optimizer with mRMR for feature selection of high-dimensional gene expression data

A robust ensemble feature selection approach to prioritize genes associated with survival outcome in high-dimensional gene expression data

Exploring features associated with the clinical outcome of interest is a rapidly advancing area of research. However, with contemporary sequencing technologies capable of identifying over thousands of genes per sample, there is a challenge in constructing efficient prediction models that balance accuracy and resource utilization. To address this challenge, researchers have developed feature selection methods to enhance performance, reduce overfitting, and ensure resource efficiency. However, applying feature selection models to survival analysis, particularly in clinical datasets characterized by substantial censoring and limited sample sizes, introduces unique challenges. We propose a robust ensemble feature selection approach integrated with group Lasso to identify compelling features and evaluate its performance in predicting survival outcomes. Our approach consistently outperforms established models across various criteria through extensive simulations, demonstrating low false discovery rates, high sensitivity, and high stability. Furthermore, we applied the approach to a colorectal cancer dataset from The Cancer Genome Atlas, showcasing its effectiveness by generating a composite score based on the selected genes to correctly distinguish different subtypes of the patients. In summary, our proposed approach excels in selecting impactful features from high-dimensional data, yielding better outcomes compared to contemporary state-of-the-art models.

Stable feature selection utilizing Graph Convolutional Neural Network and Layer-wise Relevance Propagation for biomarker discovery in breast cancer

High-throughput technologies are becoming increasingly important in discovering prognostic biomarkers and in identifying novel drug targets. With Mammaprint, Oncotype DX, and many other prognostic molecular signatures breast cancer is one of the paradigmatic examples of the utility of high-throughput data to deliver prognostic biomarkers, that can be represented in a form of a rather short gene list. Such gene lists can be obtained as a set of features (genes) that are important for the decisions of a Machine Learning (ML) method applied to high-dimensional gene expression data. Several studies have identified predictive gene lists for patient prognosis in breast cancer, but these lists are unstable and have only a few genes in common. Instability of feature selection impedes biological interpretability: genes that are relevant for cancer pathology should be members of any predictive gene list obtained for the same clinical type of patients. Stability and interpretability of selected features can be improved by including information on molecular networks in ML methods. Graph Convolutional Neural Network (GCNN) is a contemporary deep learning approach applicable to gene expression data structured by a prior knowledge molecular network. Layer-wise Relevance Propagation (LRP) and SHapley Additive exPlanations (SHAP) are methods to explain individual decisions of deep learning models. We used both GCNN+LRP and GCNN+SHAP techniques to construct feature sets by aggregating individual explanations. We suggest a methodology to systematically and quantitatively analyze the stability, the impact on the classification performance, and the interpretability of the selected feature sets. We used this methodology to compare GCNN+LRP to GCNN+SHAP and to more classical ML-based feature selection approaches. Utilizing a large breast cancer gene expression dataset we show that, while feature selection with SHAP is useful in applications where selected features have to be impactful for classification performance, among all studied methods GCNN+LRP delivers the most stable (reproducible) and interpretable gene lists.

Predicting drug activity against cancer through genomic profiles and SMILES

Due to the constant increase in cancer rates, the disease has become a leading cause of death worldwide, enhancing the need for its detection and treatment. In the era of personalized medicine, the main goal is to incorporate individual variability in order to choose more precisely which therapy and prevention strategies suit each person. However, predicting the sensitivity of tumors to anticancer treatments remains a challenge. In this work, we propose two deep neural network models to predict the impact of anticancer drugs in tumors through the half-maximal inhibitory concentration (IC50). These models join biological and chemical data to apprehend relevant features of the genetic profile and the drug compounds, respectively. In order to predict the drug response in cancer cell lines, this study employed different DL methods, resorting to Recurrent Neural Networks (RNNs) and Convolutional Neural Networks (CNNs). In the first stage, two autoencoders were pre-trained with high-dimensional gene expression and mutation data of tumors. Afterward, this genetic background is transferred to the prediction models that return the IC50 value that portrays the potency of a substance in inhibiting a cancer cell line. When comparing RSEM Expected counts and TPM as methods for displaying gene expression data, RSEM has been shown to perform better in deep models and CNNs model can obtain better insight in these types of data. Moreover, the obtained results reflect the effectiveness of the extracted deep representations in the prediction of the IC50 value that portrays the potency of a substance in inhibiting a tumor, achieving a performance of a mean squared error of 1.06 and surpassing previous state-of-the-art models.

Autosurv: interpretable deep learning framework for cancer survival analysis incorporating clinical and multi-omics data

Accurate prognosis for cancer patients can provide critical information for optimizing treatment plans and improving life quality. Combining omics data and demographic/clinical information can offer a more comprehensive view of cancer prognosis than using omics or clinical data alone and can also reveal the underlying disease mechanisms at the molecular level. In this study, we developed and validated a deep learning framework to extract information from high-dimensional gene expression and miRNA expression data and conduct prognosis prediction for breast cancer and ovarian-cancer patients using multiple independent multi-omics datasets. Our model achieved significantly better prognosis prediction than the current machine learning and deep learning approaches in various settings. Moreover, an interpretation method was applied to tackle the “black-box” nature of deep neural networks and we identified features (i.e., genes, miRNA, demographic/clinical variables) that were important to distinguish predicted high- and low-risk patients. The significance of the identified features was partially supported by previous studies.

FG-HFS: A feature filter and group evolution hybrid feature selection algorithm for high-dimensional gene expression data

High dimensional and small samples characterize gene expression data and contain a large number of genes unrelated to disease. Feature selection improves the efficiency of disease diagnosis by selecting a small number of important genes. Unfortunately, existing algorithms do not consider the correlation between features, and search algorithms tend to fall into the local optimal solution in the feature search process. To this end, this paper proposes a feature filter and group evolution hybrid feature selection algorithm (FG-HFS) for high-dimensional gene expression data. Unlike existing algorithms, we propose using spectral clustering to group redundant features into a group. Then, we propose a redundant feature filter algorithm. According to the principle of approximate Markov blanket, grouped feature groups are filtered to delete these redundant features. Among them, filtered features are evenly divided by density according to the feature exponential strategy. Most importantly, we propose using the group evolution multi-objective genetic algorithm to search the filtered feature subsets and evaluate the candidate feature subsets according to the in-group and out-group so as to select the feature subsets with the highest accuracy and the least number. Experimental results show that the average accuracy (ACC) and Matthews correlation coefficient (MCC) indexes of the selected feature subsets (FSs) by the FG-HFS algorithm on 5 gene expression datasets are 92.76% and 88.76%, respectively, which are significantly better than the existing algorithms. In addition, the FSs and ACC/FSs indexes of the FG-HFS algorithm are also better than the existing algorithms, which fully proves the superiority of the FG-HFS algorithm. More importantly, the Wilcoxon and Friedman statistical experiments results show that the feature selection effect of FG-HFS algorithm is significantly better than that of existing algorithms, no matter in pairwise comparison or multiple comparison.

Proposed Two-Steps Procedure of Classification High Dimensional Data with Regularized Logistic Regression

The field of Bioinformatics has developed in response to the rapid increase in biological data, particularly high-dimensional gene expression data. Bioinformatics utilizes optimization, computational science, and statistical methods to effectively address challenges in the field of molecular biology. Numerous genes (variables) in gene expression are irrelevant to their study. Gene selection has been demonstrated to be an effective means of enhancing the performance of numerous methods of classification. The job of acquiring significant variables via the use of ranking variable selection (RVS) techniques and then picking the most effective classifier is an enormous challenge in the context of high-dimensional data. in this study, we proposed a new ranking filter method using smooth clipped absolute deviation depending on the resampling technique (RSVS) to obtain a proficient subset of genes with strong classification abilities. This is achieved by merging A screening technique employed as a filtering method in conjunction with Regularized Logistic Regression, such as LASSO,ALASSO,ENET, and MCP. The study involved the utilization of both simulated and real datasets to conduct an empirical evaluation of the proposed approach. The findings indicated that the proposed method outperformed other established methods. it was tested using three publicly data sets about Cancer. The Results demonstrate that the suggested approach is highly effective and viable, thus showing a strong level of performance with regards to accuracy, geometric mean, and the area under the curve. Furthermore, The findings suggest that the genes most often chosen are physiologically associated with the specific form of cancer. Therefore, the method that has been suggested has potential advantages for the classification of cancer via the use of DNA gene expression data within a clinical setting.

An embedded feature selection method based on generalized classifier neural network for cancer classification

The selection of relevant genes plays a vital role in classifying high-dimensional microarray gene expression data. Sparse group Lasso and its variants have been employed for gene selection to capture the interactions of genes within a group. Most of the embedded methods are linear sparse learning models that fail to capture the non-linear interactions. Additionally, very less attention is given to solving multi-class problems. The existing methods create overlapping groups, which further increases dimensionality. The paper proposes a neural network-based embedded feature selection method that can represent the non-linear relationship. In an effort toward an explainable model, a generalized classifier neural network (GCNN) is adopted as the model for the proposed embedded feature selection. GCNN has well-defined architecture in terms of the number of layers and neurons within each layer. Each layer has a distinct functionality, eliminating the obscure nature of most neural networks. The paper proposes a feature selection approach called Weighted GCNN (WGCNN) that embeds feature weighting as a part of training the neural network. Since the gene expression data comprises a large number of features, to avoid overfitting of the model a statistical guided dropout is implemented at the input layer. The proposed method works for binary as well as multi-class classification problems likewise. Experimental validation is carried out on seven microarray datasets on three learning models and compared with six state-of-art methods that are popularly employed for feature selection. The WGCNN performs well in terms of the F1 score and the number of features selected.

Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus.

Most childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%. Thus, there is urgent need to decipher and target immune mechanisms that drive cLN. Despite the clear role of autoantibody production in SLE, targeted B cell therapies such as rituximab (anti-CD20) and belimumab (anti-BAFF) have shown only modest efficacy in cLN. While many studies have linked dysregulation of germinal center formation to SLE pathogenesis, other work supports a role for extrafollicular B cell activation in generation of pathogenic antibody secreting cells. However, whether extrafollicular B cell subsets and their T cell collaborators play a role in specific organ involvement in cLN and/or track with disease activity remains unknown. We analyzed high-dimensional mass cytometry and gene expression data from 24 treatment naïve cSLE patients at the time of diagnosis and longitudinally, applying novel computational tools to identify abnormalities associated with clinical manifestations (cLN) and disease activity (SLEDAI). cSLE patients have an extrafollicular B cell expansion signature, with increased frequency of i) DN2, ii) Bnd2, iii) plasmablasts, and iv) peripheral T helper cells. Most importantly, we discovered that this extrafollicular signature correlates with disease activity in cLN, supporting extrafollicular T/B interactions as a mechanism underlying pediatric renal pathogenesis. This study integrates established and emerging themes of extrafollicular B cell involvement in SLE by providing evidence for extrafollicular B and peripheral T helper cell expansion, along with elevated type 1 IFN activation, in a homogeneous cohort of treatment-naïve cSLE patients, a point at which they should display the most extreme state of their immune dysregulation.

Designs for the simultaneous inference of concentration–response curves

BackgroundAn important problem in toxicology in the context of gene expression data is the simultaneous inference of a large number of concentration–response relationships. The quality of the inference substantially depends on the choice of design of the experiments, in particular, on the set of different concentrations, at which observations are taken for the different genes under consideration. As this set has to be the same for all genes, the efficient planning of such experiments is very challenging. We address this problem by determining efficient designs for the simultaneous inference of a large number of concentration–response models. For that purpose, we both construct a D-optimality criterion for simultaneous inference and a K-means procedure which clusters the support points of the locally D-optimal designs of the individual models.ResultsWe show that a planning of experiments that addresses the simultaneous inference of a large number of concentration–response relationships yields a substantially more accurate statistical analysis. In particular, we compare the performance of the constructed designs to the ones of other commonly used designs in terms of D-efficiencies and in terms of the quality of the resulting model fits using a real data example dealing with valproic acid. For the quality comparison we perform an extensive simulation study.ConclusionsThe design maximizing the D-optimality criterion for simultaneous inference improves the inference of the different concentration–response relationships substantially. The design based on the K-means procedure also performs well, whereas a log-equidistant design, which was also included in the analysis, performs poorly in terms of the quality of the simultaneous inference. Based on our findings, the D-optimal design for simultaneous inference should be used for upcoming analyses dealing with high-dimensional gene expression data.

Identifying a developmental transition in honey bees using gene expression data.

In many organisms, interactions among genes lead to multiple functional states, and changes to interactions can lead to transitions into new states. These transitions can be related to bifurcations (or critical points) in dynamical systems theory. Characterizing these collective transitions is a major challenge for systems biology. Here, we develop a statistical method for identifying bistability near a continuous transition directly from high-dimensional gene expression data. We apply the method to data from honey bees, where a known developmental transition occurs between bees performing tasks in the nest and leaving the nest to forage. Our method, which makes use of the expected shape of the distribution of gene expression levels near a transition, successfully identifies the emergence of bistability and links it to genes that are known to be involved in the behavioral transition. This proof of concept demonstrates that going beyond correlative analysis to infer the shape of gene expression distributions might be used more generally to identify collective transitions from gene expression data.

NNFSRR: Nearest Neighbor Feature Selection and Redundancy Removal Method for Nearest Neighbor Search in Microarray Gene Expression Data

INTRODUCTION: Gene expression data analysis is a critical aspect of disease prediction and classification, playing a pivotal role in the field of bioinformatics and biomedical research. High-dimensional gene expression datasets hold a wealth of information, but their effective utilization is hindered by the presence of irrelevant dimensions and noise. The challenge lies in extracting meaningful features from these datasets to enhance the accuracy of disease prediction and classification while maintaining computational efficiency.
 Feature selection is a crucial step in addressing these challenges, as it aims to identify and retain only the most informative characteristics from large high-dimensional microarray datasets. In the context of microarray gene expression data, characterized by its substantial dimensionality, selecting relevant features is essential for efficient nearest neighbor search, a fundamental component of various analytical tasks in bioinformatics and data mining.
 Existing feature selection methods in high-dimensional data often face issues related to the trade-off between search accuracy and computational efficiency. This paper introduces a novel approach, the Nearest Neighbor Feature Selection with Symmetrical Uncertainty-based Redundancy Removal (NNFSRR) method, designed to enhance the classification of microarray gene expression data through feature selection. The NNFSRR method focuses on reducing the dimensionality of the dataset by identifying and removing redundant features, allowing subsequent searches to operate solely on relevant dimensions.
 OBJECTIVES: The primary goal is to evaluate the NNFSRR method's effectiveness in improving nearest neighbor search in microarray gene expression datasets by reducing dimensionality. This method utilizes Symmetrical Uncertainty-based correlation between dimensions for feature selection and aims to enhance accuracy and efficiency compared to existing methods.
 METHODS: The NNFSRR method uses Symmetrical Uncertainty to identify and remove redundant features from microarray gene expression datasets. Reduced datasets are used for nearest neighbor search, improving accuracy and efficiency. Experiments are conducted using real-world datasets, and comparisons with existing methods are made based on search time and accuracy.
 RESULTS: The NNFSRR method demonstrates improved nearest neighbor search performance, outperforming basic brute force methods and existing feature selection techniques. Selected feature sets exhibit strong class associations while minimizing feature correlations, enhancing classification precision.
 CONCLUSION: In conclusion, the NNFSRR method presents a promising approach to address the challenges posed by high-dimensional gene expression data. It effectively reduces dimensionality, improves search accuracy, and enhances the efficiency of nearest neighbor search. Our experimental results demonstrate that this method outperforms existing techniques in terms of search time and accuracy, making it a valuable tool for applications in bioinformatics, data mining, pattern recognition, and biological information retrieval. The NNFSRR method holds the potential to advance our understanding of complex biological processes and support more accurate disease prediction and classification.

Gene selection with Game Shapley Harris hawks optimizer for cancer classification

Cancer disease has been classified as a perilous disease for humans, being the second leading cause of death globally. Even advanced-stage diagnosis may not be effective in preventing patient mortality. Therefore, it is important to establish a sustainable framework that predicts reliable estimates for an early cancer diagnosis. In this paper, a new two-phase feature (gene) selection approach is presented. In the first phase, the kernel Shapley value (kSV) that is based on the cooperative game-theoretic feature extraction approach is utilized to extract the important feature from the high dimensional gene expression data. In the second phase, Harris hawks optimizer (HHO) algorithm is utilized to further optimize the most effective feature extracted by kSV. Next, to evaluate the effectiveness of our proposed algorithm, we conduct extensive experiments on eight benchmark high-dimensional gene expression datasets, comparing them with other state-of-the-art techniques. We employ three classifiers, namely support vector machines (SVM), Naive Bayes (NB), and K-nearest neighbors (KNN), to assess the selected genes efficacy and their impact on classification accuracy. The experimental results demonstrate that the proposed method, particularly when combined with the SVM classifier, outperforms other gene selection methods. The evaluation metrics, including accuracy, precision, recall, F1-score, ROC-AUC, box plot, and radar plot, consistently indicate the superiority of kSV-HHO across all tested datasets. Moreover, the comparative and statistical analysis reveals that our proposed method excels in identifying the most relevant features for cancer diagnosis compared to other gene selection approaches. This makes our framework a valuable tool for cancer research and clinical practice, potentially enhancing the accuracy of early cancer diagnosis using high-dimensional gene expression biomedical data.

Classification of hepatotoxicity of compounds based on cytotoxicity assays is improved by additional interpretable summaries of high-dimensional gene expression data

Established cytotoxicity assays are commonly used for assessing the hepatotoxic risk of a compound. The addition of gene expression measurements from high-dimensional RNAseq experiments offers the potential for improved classification. However, it is generally not clear how best to summarize the high-dimensional gene measurements into meaningful variables. We propose several intuitive methods for dimension reduction of gene expression measurements toward interpretable variables and explore their relevance in predicting hepatotoxicity, using a dataset with 60 compounds.Different advanced statistical learning algorithms are evaluated as classification methods and their performances are compared on the dataset. The best predictions are achieved by tree-based methods such as random forest and xgboost, and tuning the parameters of the algorithm helps to improve the classification accuracy. It is shown that the simultaneous use of data from cytotoxicity assays and from gene expression variables summarized in different ways has a synergistic effect and leads to a better prediction of hepatotoxicity than both sets of variables individually. Further, when gene expression data are summarized, different strategies for the generation of interpretable variables contribute to the overall improved prediction quality. When considering cytotoxicity assays alone, the best classification method yields a mean accuracy of 0.757, while the same classification method and an optimal choice of variables yields a mean accuracy of 0.811. The overall best value for the mean accuracy is 0.821.

Leveraging cell-cell similarity for high-performance spatial and temporal cellular mappings from gene expression data

Single-cell trajectory mapping and spatial reconstruction are two important developments in life science and provide a unique means to decode heterogeneous tissue formation, cellular dynamics, and tissue developmental processes. The success of these techniques depends critically on the performance of analytical tools used for high-dimensional (HD) gene expression data processing. Existing methods discern the patterns of the data without explicitly considering the underlying biological characteristics of the system, often leading to suboptimal solutions. Here, we present a cell-cell similarity-driven framework of genomic data analysis for high-fidelity spatial and temporal cellular mappings. The approach exploits the similarity features of the cells to discover discriminative patterns of the data. We show that for a wide variety of datasets, the proposed approach drastically improves the accuracies of spatial and temporal mapping analyses compared with state-of-the-art techniques.

Categorical Data Analysis for High-Dimensional Sparse Gene Expression Data.

Categorical data analysis becomes challenging when high-dimensional sparse covariates are involved, which is often the case for omics data. We introduce a statistical procedure based on multinomial logistic regression analysis for such scenarios, including variable screening, model selection, order selection for response categories, and variable selection. We perform our procedure on high-dimensional gene expression data with 801 patients, 2426 genes, and five types of cancerous tumors. As a result, we recommend three finalized models: one with 74 genes achieves extremely low cross-entropy loss and zero predictive error rate based on a five-fold cross-validation; and two other models with 31 and 4 genes, respectively, are recommended for prognostic multi-gene signatures.

ForestSubtype: a cancer subtype identifying approach based on high-dimensional genomic data and a parallel random forest

BackgroundCancer subtype classification is helpful for personalized cancer treatment. Although, some approaches have been developed to classifying caner subtype based on high dimensional gene expression data, it is difficult to obtain satisfactory classification results. Meanwhile, some cancers have been well studied and classified to some subtypes, which are adopt by most researchers. Hence, this priori knowledge is significant for further identifying new meaningful subtypes.ResultsIn this paper, we present a combined parallel random forest and autoencoder approach for cancer subtype identification based on high dimensional gene expression data, ForestSubtype. ForestSubtype first adopts the parallel RF and the priori knowledge of cancer subtype to train a module and extract significant candidate features. Second, ForestSubtype uses a random forest as the base module and ten parallel random forests to compute each feature weight and rank them separately. Then, the intersection of the features with the larger weights output by the ten parallel random forests is taken as our subsequent candidate features. Third, ForestSubtype uses an autoencoder to condenses the selected features into a two-dimensional data. Fourth, ForestSubtype utilizes k-means++ to obtain new cancer subtype identification results. In this paper, the breast cancer gene expression data obtained from The Cancer Genome Atlas are used for training and validation, and an independent breast cancer dataset from the Molecular Taxonomy of Breast Cancer International Consortium is used for testing. Additionally, we use two other cancer datasets for validating the generalizability of ForestSubtype. ForestSubtype outperforms the other two methods in terms of the distribution of clusters, internal and external metric results. The open-source code is available at https://github.com/lffyd/ForestSubtype.ConclusionsOur work shows that the combination of high-dimensional gene expression data and parallel random forests and autoencoder, guided by a priori knowledge, can identify new subtypes more effectively than existing methods of cancer subtype classification.

Seiðr: Efficient calculation of robust ensemble gene networks

Gene regulatory and gene co-expression networks are powerful research tools for identifying biological signal within high-dimensional gene expression data. In recent years, research has focused on addressing shortcomings of these techniques with regard to the low signal-to-noise ratio, non-linear interactions and dataset dependent biases of published methods. Furthermore, it has been shown that aggregating networks from multiple methods provides improved results. Despite this, few useable and scalable software tools have been implemented to perform such best-practice analyses. Here, we present Seidr (stylized Seiðr), a software toolkit designed to assist scientists in gene regulatory and gene co-expression network inference. Seidr creates community networks to reduce algorithmic bias and utilizes noise corrected network backboning to prune noisy edges in the networks.Using benchmarks in real-world conditions across three eukaryotic model organisms, Saccharomyces cerevisiae, Drosophila melanogaster, and Arabidopsis thaliana, we show that individual algorithms are biased toward functional evidence for certain gene-gene interactions. We further demonstrate that the community network is less biased, providing robust performance across different standards and comparisons for the model organisms.Finally, we apply Seidr to a network of drought stress in Norway spruce (Picea abies (L.) H. Krast) as an example application in a non-model species. We demonstrate the use of a network inferred using Seidr for identifying key components, communities and suggesting gene function for non-annotated genes.

Cell-type classification of cancer single-cell RNA-seq data using the Subsemble ensemble-based machine learning classifier

Background The advent of single-cell RNA sequencing (scRNA-seq) has provided a high-resolution overview of the cellular heterogeneity of different tissue types. Manual cell type annotation of gene expression datasets remains a useful but time-intensive task. Ensemble machine learning methods leverage the predictive power of multiple classifiers and can be applied to classify high-dimensional gene expression data. Here, we present a novel application of the Subsemble supervised ensemble machine learning classifier used to classify novel cells with known cell type labels using gene expression data. Methods First, we tested the classification performance of different pre-processing steps used to normalize and upsample the training dataset for the Subsemble using a colorectal cancer dataset. Second, we conducted a cross-validated performance benchmark of the Subsemble classifier compared to nine other cell type classification methods across five metrics tested, using an acute myeloid leukemia dataset. Third, we conducted a comparative performance benchmark of the Subsemble classifier using a patient-based leave-one-out cross-validation scheme. Rank normalized scores were calculated for each classifier to aggregate performance across multiple metrics. Results The Subsemble classifier performed best when trained on a dataset that was log-transformed then upsampled to generate balanced class distributions. The Subsemble classifier was consistently the top-ranked classifier across five classification performance metrics compared to the nine other baseline classifiers and showed an improvement in performance as the training dataset increased. When tested using the patient-based leave-one-out cross-validation scheme, the Subsemble was the top-ranked classifier based on rank normalized scores. Conclusions Our proof-of-concept study showed that the Subsemble classifier can be used to accurately predict known cell type labels from single-cell gene expression data. The top-ranked classification performance of the Subsemble across two validation datasets, two cross-validation schemes, and five performance metrics motivates future development of accurate ensemble classifiers of scRNA-seq datasets.