Cell type assignment is a major challenge for all types of high throughput single cell data. In many cases such assignment requires the repeated manual use of external and complementary data sources. To improve the ability to uniformly assign cell types across large consortia, platforms and modalities, we developed Cellar, a software tool that provides interactive support to all the different steps involved in the assignment and dataset comparison process. We discuss the different methods implemented by Cellar, how these can be used with different data types, how to combine complementary data types and how to analyze and visualize spatial data. We demonstrate the advantages of Cellar by using it to annotate several HuBMAP datasets from multi-omics single-cell sequencing and spatial proteomics studies. Cellar is open-source and includes several annotated HuBMAP datasets.

Cellular senescence is a major hallmark of aging. Senescence is defined as an irreversible growth arrest observed when cells are exposed to a variety of stressors including DNA damage, oxidative stress, or nutrient deprivation. While senescence is a well-established driver of aging and age-related diseases, it is a highly heterogeneous process with significant variations across organisms, tissues, and cell types. The relatively low abundance of senescence in healthy aged tissues represents a major challenge to studying senescence in a given organ, including the human lung. To overcome this limitation, we developed a Positive-Unlabeled (PU) learning framework to generate a comprehensive senescence marker gene list in human lungs (termed SenSet) using the largest publicly available single-cell lung dataset, the Human Lung Cell Atlas (HLCA). We validated SenSet in a highly complex ex vivo human 3D lung tissue culture model subjected to the senescence inducers bleomycin, doxorubicin, or irradiation, and established its sensitivity and accuracy in characterizing senescence. Using SenSet, we identified and validated cell-type specific senescence signatures in distinct lung cell populations upon aging and environmental exposures. Our study presents the first comprehensive analysis of senescent cells in the healthy aging lung and uncovers cell-specific gene signatures of senescence, presenting fundamental implications for our understanding of major lung diseases, including cancer, fibrosis, chronic obstructive pulmonary disease, or asthma.

Markers are increasingly being used for several high-throughput data analysis and experimental design tasks. Examples include the use of markers for assigning cell types in scRNA-seq studies, for deconvolving bulk gene expression data, and for selecting marker proteins in single-cell spatial proteomics studies. Most marker selection methods focus on differential expression (DE) analysis. Although such methods work well for data with a few non-overlapping marker sets, they are not appropriate for large atlas-size datasets where several cell types and tissues are considered. To address this, we define the phenotype cover (PC) problem for marker selection and present algorithms that can improve the discriminative power of marker sets. Analysis of these sets on several marker-selection tasks suggests that these methods can lead to solutions that accurately distinguish different phenotypes in the data.

Motivation: Analysis of time series transcriptomics data from clinical trials is challenging. Such studies usually profile very few time points from several individuals with varying response patterns and dynamics. Current methods for these datasets are mainly based on linear, global orderings using visit times which do not account for the varying response rates and subgroups within a patient cohort. Results: We developed a new method that utilizes multi-commodity flow algorithms for trajectory inference in large scale clinical studies. Recovered trajectories satisfy individual-based timing restrictions while integrating data from multiple patients. Testing the method on multiple drug datasets demonstrated an improved performance compared to prior approaches suggested for this task, while identifying novel disease subtypes that correspond to heterogeneous patient response patterns. Availability and implementation: The source code and instructions to download the data have been deposited on GitHub at https://github.com/euxhenh/Truffle.

Motivation: Gene regulation is a dynamic process that underlies all aspects of human development, disease response, and other biological processes. The reconstruction of temporal gene regulatory networks has conventionally relied on regression analysis, graphical models, or other types of relevance networks. With the large increase in time series single-cell data, new approaches are needed to address the unique scale and nature of these data for reconstructing such networks. Results: Here, we develop a deep neural network, Marlene, to infer dynamic graphs from time series single-cell gene expression data. Marlene constructs directed gene networks using a self-attention mechanism where the weights evolve over time using recurrent units. By employing meta learning, the model is able to recover accurate temporal networks even for rare cell types. In addition, Marlene can identify gene interactions relevant to specific biological responses, including COVID-19 immune response, fibrosis, and aging, paving the way for potential treatments. Availability and implementation: The code used to train Marlene is available at https://github.com/euxhenh/Marlene.

Background: Artificial intelligence (AI), the overarching field that includes machine learning (ML) and its subfield deep learning (DL), is rapidly transforming clinical research by enabling the analysis of high-dimensional data and automating the output of diagnostic and prognostic tests. As clinical trials become increasingly complex and costly, ML-based approaches (especially DL for image and signal data) offer promising solutions, although they require new approaches in clinical education. Objective: Explore current and emerging AI applications in oncology and cardiology, highlight real-world use cases, and discuss the challenges and future directions for responsible AI adoption. Methods: This narrative review summarizes various aspects of AI technology in clinical research, exploring its promise, use cases, and its limitations. The review was based on a literature search in PubMed covering publications from 2019 to 2025. Search terms included “artificial intelligence”, “machine learning”, “deep learning”, “oncology”, “cardiology”, “digital twin”. and “AI-ECG”. Preference was given to studies presenting validated or clinically applicable AI tools, while non-English articles, conference abstracts, and gray literature were excluded. Results: AI demonstrates significant potential in improving diagnostic accuracy, facilitating biomarker discovery, and detecting disease at an early stage. In clinical trials, AI improves patient stratification, site selection, and virtual simulations via digital twins. However, there are still challenges in harmonizing data, validating models, cross-disciplinary training, ensuring fairness, explainability, as well as the robustness of gold standards to which AI models are built. Conclusions: The integration of AI in clinical research can enhance efficiency, reduce costs, and facilitate clinical research as well as lead the way towards personalized medicine. Realizing this potential requires robust validation frameworks, transparent model interpretability, and collaborative efforts among clinicians, data scientists, and regulators. Interoperable data systems and cross-disciplinary education will be critical to enabling the integration of scalable, ethical, and trustworthy AI into healthcare.