Scientists discover how a vitamin A byproduct may weaken immune responses against cancer, potentially explaining why some immunotherapies fail in patients.

Respiratory viral infections pose a global health burden, yet the cellular immune responses driving protection or pathology remain unclear. Natural infection cohorts often lack pre-exposure baseline data and structured temporal sampling. In contrast, inoculation and vaccination trials generate insightful longitudinal transcriptomic data. However, the scattering of these datasets across platforms, along with inconsistent metadata and preprocessing procedure, hinders AI-driven discovery. To address these challenges, we developed the Human Respiratory Viral Immunization LongitudinAl Gene Expression (HR-VILAGE-3K3M) repository: an AI-ready, rigorously curated dataset that integrates 14,136 RNA-seq profiles from 3,178 subjects across 66 studies encompassing over 2.56 million cells. Spanning vaccination, inoculation, and mixed exposures, the dataset includes microarray, bulk RNA-seq, and single-cell RNA-seq from whole blood, PBMCs, and nasal swabs, sourced from GEO, ImmPort, and ArrayExpress. We harmonized subject-level metadata, standardized outcome measures, applied unified preprocessing pipelines with rigorous quality control, and aligned all data to official gene symbols. To demonstrate the utility of HR-VILAGE-3K3M, we performed predictive modeling of vaccine responders and evaluated batch-effect correction methods. Beyond these initial demonstrations, it supports diverse systems immunology applications and benchmarking of feature selection and transfer learning algorithms. Its scale and heterogeneity also make it ideal for pretraining foundation models of the human immune response and for advancing multimodal learning frameworks. As the largest longitudinal transcriptomic resource for human respiratory viral immunization, it provides an accessible platform for reproducible AI-driven research, accelerating systems immunology and vaccine development against emerging viral threats.

As cancer cases continue to rise, with a 2023 study from Zhejiang and Harvard predicting a 31 percent increase in cases and a 21 percent increase in deaths by 2030, the need to find more effective treatments for cancer is greater than ever before. Traditional approaches to treating cancer, such as chemotherapy, often kill healthy cells because of their lack of targetability. In contrast, personalized cancer vaccines can utilize neoepitopes - distinctive peptides on cancer cells that are often missed by the body's immune system - that have strong binding affinities to a patient's MHC to provide a more targeted treatment approach. The selection of optimal neoepitopes that elicit an immune response is a time-consuming and costly process due to the required inputs of modern predictive methods. This project aims to facilitate faster, cheaper, and more accurate neoepitope binding predictions using Feed Forward Neural Networks (FFNN) and Recurrent Neural Networks (RNN). To address this, NEO was created. NEO requires next-generation sequencing data and uses a stacking ensemble method by calculating scores from state-of-the-art models (MHCFlurry 1.6, NetMHCstabpan 1.0, and IEDB). The model's architecture includes an FFNN and an RNN with LSTM layers capable of analyzing both sequential and non-sequential data. The results from both models are aggregated to produce predictions. Using this model, personalized cancer vaccines can be produced with improved results (AUC = 0.9166, recall = 91.67 percent).

In this paper, we introduce QuST-LLM, an innovative extension of QuPath that utilizes the capabilities of large language models (LLMs) to analyze and interpret spatial transcriptomics (ST) data. In addition to simplifying the intricate and high-dimensional nature of ST data by offering a comprehensive workflow that includes data loading, region selection, gene expression analysis, and functional annotation, QuST-LLM employs LLMs to transform complex ST data into understandable and detailed biological narratives based on gene ontology annotations, thereby significantly improving the interpretability of ST data. Consequently, users can interact with their own ST data using natural language. Hence, QuST-LLM provides researchers with a potent functionality to unravel the spatial and functional complexities of tissues, fostering novel insights and advancements in biomedical research. QuST-LLM is a part of QuST project. The source code is hosted on GitHub and documentation is available at (https://github.com/huangch/qust).

The typical phases of Bayesian network (BN) structured development include specification of purpose and scope, structure development, parameterisation and validation. Structure development is typically focused on qualitative issues and parameterisation quantitative issues, however there are qualitative and quantitative issues that arise in both phases. A common step that occurs after the initial structure has been developed is to perform a rough parameterisation that only captures and illustrates the intended qualitative behaviour of the model. This is done prior to a more rigorous parameterisation, ensuring that the structure is fit for purpose, as well as supporting later development and validation. In our collective experience and in discussions with other modellers, this step is an important part of the development process, but is under-reported in the literature. Since the practice focuses on qualitative issues, despite being quantitative in nature, we call this step qualitative parameterisation and provide an outline of its role in the BN development process.

This study introduces the Supervised Magnitude-Altitude Scoring (SMAS) methodology, a machine learning-based approach, for analyzing gene expression data obtained from nonhuman primates (NHPs) infected with Ebola virus (EBOV). We utilize a comprehensive dataset of NanoString gene expression profiles from Ebola-infected NHPs, deploying the SMAS system for nuanced host-pathogen interaction analysis. SMAS effectively combines gene selection based on statistical significance and expression changes, employing linear classifiers such as logistic regression to accurately differentiate between RT-qPCR positive and negative NHP samples. A key finding of our research is the identification of IFI6 and IFI27 as critical biomarkers, demonstrating exceptional predictive performance with 100% accuracy and Area Under the Curve (AUC) metrics in classifying various stages of Ebola infection. Alongside IFI6 and IFI27, genes, including MX1, OAS1, and ISG15, were significantly upregulated, highlighting their essential roles in the immune response to EBOV. Our results underscore the efficacy of the SMAS method in revealing complex genetic interactions and response mechanisms during EBOV infection. This research provides valuable insights into EBOV pathogenesis and aids in developing more precise diagnostic tools and therapeutic strategies to address EBOV infection in particular and viral infection in general.

Alzheimer's disease has an increasing prevalence in the population world-wide, yet current diagnostic methods based on recommended biomarkers are only available in specialized clinics. Due to these circumstances, Alzheimer's disease is usually diagnosed late, which contrasts with the currently available treatment options that are only effective for patients at an early stage. Blood-based biomarkers could fill in the gap of easily accessible and low-cost methods for early diagnosis of the disease. In particular, immune-based blood-biomarkers might be a promising option, given the recently discovered cross-talk of immune cells of the central nervous system with those in the peripheral immune system. With the help of machine learning algorithms and mechanistic modeling approaches, such as agent-based modeling, an in-depth analysis of the simulation of cell dynamics is possible as well as of high-dimensional omics resources indicative of pathway signaling changes. Here, we give a background on advances in research on brain-immune system cross-talk in Alzheimer's disease and review recent machine learning and mechanistic modeling approaches which leverage modern omics technologies for blood-based immune system-related biomarker discovery.

COVID-19 has a spectrum of disease severity, ranging from asymptomatic to requiring hospitalization. Understanding the mechanisms driving disease severity is crucial for developing effective treatments and reducing mortality rates. One way to gain such understanding is using a multi-class classification framework, in which patients' biological features are used to predict patients' severity classes. In this severity classification problem, it is beneficial to prioritize the identification of more severe classes and control the "under-classification" errors, in which patients are misclassified into less severe categories. The Neyman-Pearson (NP) classification paradigm has been developed to prioritize the designated type of error. However, current NP procedures are either for binary classification or do not provide high probability controls on the prioritized errors in multi-class classification. Here, we propose a hierarchical NP (H-NP) framework and an umbrella algorithm that generally adapts to popular classification methods and controls the under-classification errors with high probability. On an integrated collection of single-cell RNA-seq (scRNA-seq) datasets for 864 patients, we explore ways of featurization and demonstrate the efficacy of the H-NP algorithm in controlling the under-classification errors regardless of featurization. Beyond COVID-19 severity classification, the H-NP algorithm generally applies to multi-class classification problems, where classes have a priority order.

Fox News' Eben Brown reports on how more companies are using A.I. technology to set retail prices based on data-driven supply-and-demand. Oncologists in the U.K. have developed an AI model to help predict whether aggressive forms of breast cancer will spread based on changes in a patient's lymph nodes. The research was published Thursday in the Journal of Pathology by Breast Cancer Now and funded by scientists at King's College of London. Secondary or "metastatic breast cancer" refers to when breast cancer cells spread to other parts of the body. Although treatable, it can't be cured.

AI can design extremely dense protein shells that could one day lead to more potent vaccines. The genetic material of viruses is housed in protein shells. Similar shells made in the lab are used in vaccines, encapsulating molecules that induce an immune response in the body. The chemical and biological properties of these artificially made shells depend on their construction – any imperfections in them, no matter how small, make them less effective, causing them to be unstable and react unpredictably inside cells. Isaac Lutz at the University of Washington in Seattle and his colleagues wanted to see if using artificial intelligence could make the design and creation of these shells more precise.