Understanding tumor cell heterogeneity and plasticity is crucial for overcoming drug resistance. Single-cell technologies enable analyzing cell states at a given condition, but catenating static cell snapshots to characterize dynamic drug responses remains challenging. Here, we propose scStateDynamics, an algorithm to infer tumor cell state dynamics and identify common drug effects by modeling single-cell level gene expression changes.
View Article and Find Full Text PDFObjectives: To develop computed tomography (CT)-based models to increase the prediction accuracy of spread through air spaces (STAS) in clinical-stage T1N0 lung adenocarcinoma.
Methods: Three cohorts of patients with stage T1N0 lung adenocarcinoma (n = 1258) were analyzed retrospectively. Two models using radiomics and deep neural networks (DNNs) were established to predict the lung adenocarcinoma STAS status.
Nucleic Acids Res
January 2025
Investigating mutations, including single nucleotide variations (SNVs), gene fusions, alternative splicing and copy number variations (CNVs), is fundamental to cancer study. Recent computational methods and biological research have demonstrated the reliability and biological significance of detecting mutations from single-cell transcriptomic data. However, there is a lack of a single-cell-level database containing comprehensive mutation information in all types of cancer.
View Article and Find Full Text PDFBioinformatics
September 2024
Motivation: Single-cell RNA sequencing (scRNA-seq) data are important for studying the laws of life at single-cell level. However, it is still challenging to obtain enough high-quality scRNA-seq data. To mitigate the limited availability of data, generative models have been proposed to computationally generate synthetic scRNA-seq data.
View Article and Find Full Text PDFMucosal Immunol
December 2024
The helper-like ILC contains various functional subsets, such as ILC1, ILC2, ILC3 and LTi cells, mediating the immune responses against viruses, parasites, and extracellular bacteria, respectively. Among them, LTi cells are also crucial for the formation of peripheral lymphoid tissues, such as lymph nodes. Our research, along with others', indicates a high proportion of LTi cells in the fetal ILC pool, which significantly decreases after birth.
View Article and Find Full Text PDFA universal coordinate system that can ensemble the huge number of cells and capture their heterogeneities is of vital importance for constructing large-scale cell atlases as references for molecular and cellular studies. Studies have shown that cells exhibit multifaceted heterogeneities in their transcriptomic features at multiple resolutions. This nature of complexity makes it hard to design a fixed coordinate system through a combination of known features.
View Article and Find Full Text PDFMotivation: In single-cell studies, principal component analysis (PCA) is widely used to reduce the dimensionality of dataset and visualize in 2D or 3D PC plots. Scientists often focus on different clusters within PC plot, overlooking the specific phenomenon, such as horse-shoe-like effect, that may reveal hidden knowledge about underlying biological dataset. This phenomenon remains largely unexplored in single-cell studies.
View Article and Find Full Text PDFWhile single-cell technologies have greatly advanced our comprehension of human brain cell types and functions, studies including large numbers of donors and multiple brain regions are needed to extend our understanding of brain cell heterogeneity. Integrating atlas-level single-cell data presents a chance to reveal rare cell types and cellular heterogeneity across brain regions. Here we present the Brain Cell Atlas, a comprehensive reference atlas of brain cells, by assembling single-cell data from 70 human and 103 mouse studies of the brain throughout major developmental stages across brain regions, covering over 26.
View Article and Find Full Text PDFThe immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (T) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and T cells was found within T cell zones of colonic lymphoid follicles.
View Article and Find Full Text PDFGenomics Proteomics Bioinformatics
May 2024
Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma (HCC). Integrated 15 transcriptomic datasets of HCC clinical samples, the first version of HCC database (HCCDB v1.0) was released in 2018.
View Article and Find Full Text PDFRecent advancements in single-cell sequencing technologies have generated extensive omics data in various modalities and revolutionized cell research, especially in the single-cell RNA and ATAC data. The joint analysis across scRNA-seq data and scATAC-seq data has paved the way to comprehending the cellular heterogeneity and complex cellular regulatory networks. Multi-omics integration is gaining attention as an important step in joint analysis, and the number of computational tools in this field is growing rapidly.
View Article and Find Full Text PDFIEEE Trans Neural Netw Learn Syst
February 2024
Node importance estimation (NIE) is the task of inferring the importance scores of the nodes in a graph. Due to the availability of richer data and knowledge, recent research interests of NIE have been dedicated to knowledge graphs (KGs) for predicting future or missing node importance scores. Existing state-of-the-art NIE methods train the model by available labels, and they consider every interested node equally before training.
View Article and Find Full Text PDFSingle-cell clustered regularly interspaced short palindromic repeats-sequencing (scCRISPR-seq) is an emerging high-throughput CRISPR screening technology where the true cellular response to perturbation is coupled with infected proportion bias of guide RNAs (gRNAs) across different cell clusters. The mixing of these effects introduces noise into scCRISPR-seq data analysis and thus obstacles to relevant studies. We developed scDecouple to decouple true cellular response of perturbation from the influence of infected proportion bias.
View Article and Find Full Text PDFProfiling spatial variations of cellular composition and transcriptomic characteristics is important for understanding the physiology and pathology of tissues. Spatial transcriptomics (ST) data depict spatial gene expression but the currently dominating high-throughput technology is yet not at single-cell resolution. Single-cell RNA-sequencing (SC) data provide high-throughput transcriptomic information at the single-cell level but lack spatial information.
View Article and Find Full Text PDFBackground: Pituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood.
Methods: We performed single-cell RNA sequencing (scRNA-seq) on 4 normal samples and 24 PitNET samples for comprehensive bioinformatics analysis.
Oncolytic viruses are multifaceted tumor killers, which can function as tumor vaccines to boost systemic antitumor immunity. In previous study, we rationally designed a synthetic oncolytic adenovirus (SynOV) harboring a synthetic gene circuit, which can kill tumors in mouse hepatocellular carcinoma (HCC) models. In this study, we demonstrated that SynOV could sense the tumor biomarkers to lyse tumors in a dosage-dependent manner, and killed PD-L1 antibody resistant tumor cells in mouse model.
View Article and Find Full Text PDFObjectives: The aim of this study was to evaluate the performance of consolidation-to-tumour ratio (CTR) and the radiomic models in two- and three-dimensional modalities for assessing radiological invasiveness in early-stage lung adenocarcinoma.
Methods: A retrospective analysis was conducted on patients with early-stage lung adenocarcinoma from Guangdong Provincial People's Hospital and Shenzhen People's Hospital. Manual delineation of pulmonary nodules along the boundary was performed on cross-sectional images to extract radiomic features.
Rapid advances in spatial transcriptomics (ST) have revolutionized the interrogation of spatial heterogeneity and increase the demand for comprehensive methods to effectively characterize spatial domains. As a prerequisite for ST data analysis, spatial domain characterization is a crucial step for downstream analyses and biological implications. Here we propose a prior-based self-attention framework for spatial transcriptomics (PAST), a variational graph convolutional autoencoder for ST, which effectively integrates prior information via a Bayesian neural network, captures spatial patterns via a self-attention mechanism, and enables scalable application via a ripple walk sampler strategy.
View Article and Find Full Text PDFCell-cell communication (CCC) is critical for determining cell fates and functions in multicellular organisms. With the advent of single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST), an increasing number of CCC inference methods have been developed. Nevertheless, a thorough comparison of their performances is yet to be conducted.
View Article and Find Full Text PDFCell-cell communication events (CEs) are mediated by multiple ligand-receptor (LR) pairs. Usually only a particular subset of CEs directly works for a specific downstream response in a particular microenvironment. We name them as functional communication events (FCEs) of the target responses.
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