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View article: A functional CAR-T cell atlas to unravel regulatory mechanisms of CAR-T therapies
A functional CAR-T cell atlas to unravel regulatory mechanisms of CAR-T therapies Open
Introduction: Over the past decade, CAR-T therapies have emerged as a groundbreaking treatment for cancer, showing remarkable efficacy in certain hematologic malignancies. However, these therapies still face important limitations, includin…
View article: An open CAR-T single-cell atlas to enable in-depth characterization and rational engineering of CAR-T products
An open CAR-T single-cell atlas to enable in-depth characterization and rational engineering of CAR-T products Open
BRIEF ABSTRACT We built a CAR-T cell functional atlas from over one million cells across 13 studies, integrating data from patients and healthy donors. The atlas captures 11 phenotypes, links infusion product composition with clinical resp…
View article: Deep generative modeling of sample-level heterogeneity in single-cell genomics
Deep generative modeling of sample-level heterogeneity in single-cell genomics Open
Single-cell genomic studies were recently conducted on hundred of samples exhibiting complex designs. These data have tremendous potential for discovering how sample- or tissue-level phenotypes relate to cellular and molecular composition.…
Preselection CD4 <sup>+</sup> CD8 <sup>+</sup> thymocytes modulate TCR responsiveness following TCRβ selection Open
Modulation of TCR sensitivity during positive selection is critical to avoid negative selection and direct thymocytes into their appropriate lineage. Thymocytes just prior to positive selection (preselection) are highly responsive to low a…
View article: CytoVI: Deep generative modeling of antibody-based single cell technologies
CytoVI: Deep generative modeling of antibody-based single cell technologies Open
Due to their robustness, dynamic range and scalability, antibody-based single cell technologies, such as flow cytometry, mass cytometry and CITE-seq, have become an irreplaceable part of routine clinics and a powerful tool for basic resear…
Aging-Associated Microbiota Drives Treg Dysfunction via TNF Signaling Open
Aging is associated with a chronic, low-grade inflammatory state referred to as inflammaging, which contributes to impaired immune regulation and increased susceptibility to disease. While regulatory T (Treg) cells are key mediators of imm…
ConvexML: Fast and Accurate Branch Length Estimation under Irreversible Mutation Models, Illustrated through Applications to CRISPR/Cas9-Based Lineage Tracing Open
Branch length estimation is a fundamental problem in statistical phylogenetics and a core component of tree reconstruction algorithms. Traditionally, general time-reversible mutation models are employed, and many software tools exist for t…
Can you trust your reconstructed lineage tree? A homoplasy-based approach for irreversible evolution Open
Phylogeny inference is a fundamental problem in computational biology, with many proposed algorithms. Emerging techniques that couple single-cell genomics with Cas9-based genome editing open the way for indepth analysis of cell phylogenies…
View article: High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer
High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer Open
Charting the spatiotemporal dynamics of cell fate determination in development and disease is a long-standing objective in biology. Here, we present the design, development, and extensive validation of PEtracer, a prime editing (PE)–based,…
View article: High-resolution spatial mapping of cell state and lineage dynamics <i>in vivo</i> with PEtracer
High-resolution spatial mapping of cell state and lineage dynamics <i>in vivo</i> with PEtracer Open
Charting the spatiotemporal dynamics of cell fate determination in development and disease is a long-standing objective in biology. Here we present the design, development, and extensive validation of PEtracer, a prime editing-based, evolv…
MEBOCOST maps metabolite-mediated intercellular communications using single-cell RNA-seq Open
Cell-cell communication (CCC) is crucial for cellular function and tissue homeostasis. Existing methods for protein-oriented CCC detection often overlook metabolite-mediated CCC (mCCC), and adapting them to mCCC analysis is challenging due…
View article: scVIVA: a probabilistic framework for representation of cells and their environments in spatial transcriptomics
scVIVA: a probabilistic framework for representation of cells and their environments in spatial transcriptomics Open
Spatial transcriptomics provides a significant advance over studies of dissociated cells in that it reveals the environment in which cells reside, thus opening the way for a more complete description of their state and function. However, m…
Towards the Next Generation of Data‐Driven Therapeutics Using Spatially Resolved Single‐Cell Technologies and Generative AI Open
Recent advances in multi‐omics and spatially resolved single‐cell technologies have revolutionised our ability to profile millions of cellular states, offering unprecedented opportunities to understand the complex molecular landscapes of h…
View article: ResolVI - addressing noise and bias in spatial transcriptomics
ResolVI - addressing noise and bias in spatial transcriptomics Open
Technologies for estimating RNA expression at high throughput, in intact tissue slices, and with high spatial resolution (spatial transcriptomics; ST) shed new light on how cells communicate and tissues function. A fundamental step common …
View article: Consensus prediction of cell type labels in single-cell data with popV
Consensus prediction of cell type labels in single-cell data with popV Open
Cell-type classification is a crucial step in single-cell sequencing analysis. Various methods have been proposed for transferring a cell-type label from an annotated reference atlas to unannotated query datasets. Existing methods for tran…
View article: VI-VS: calibrated identification of feature dependencies in single-cell multiomics
VI-VS: calibrated identification of feature dependencies in single-cell multiomics Open
Unveiling functional relationships between various molecular cell phenotypes from data using machine learning models is a key promise of multiomics. Existing methods either use flexible but hard-to-interpret models or simpler, misspecified…
Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumour growth and metastasis Open
Tumour progression is driven by dynamic interactions between cancer cells and their surrounding microenvironment. Investigating the spatiotemporal evolution of tumours can provide crucial insights into how intrinsic changes within cancer c…
Tree reconstruction guarantees from CRISPR-Cas9 lineage tracing data using Neighbor-Joining Open
CRISPR-Cas9 based lineage tracing technologies have enabled the reconstruction of single-cell phylo- genies from transcriptional readouts. However, developing tree-reconstruction algorithms with theoretical guarantees in this setting is ch…
View article: The glycolytic reaction PGAM unexpectedly restrains Th17 pathogenicity and Th17-dependent autoimmunity
The glycolytic reaction PGAM unexpectedly restrains Th17 pathogenicity and Th17-dependent autoimmunity Open
Glucose metabolism is a critical regulator of T cell function, largely thought to support their activation and effector differentiation. Here, we investigate the relevance of individual glycolytic reactions in determining the pathogenicity…
View article: NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids
NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids Open
As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model o…
View article: Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span
Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span Open
During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity. However, their functional role in humans has largely been defined from blood. Here, we analyzed the phenotype, transcriptome, fun…
View article: Comprehensive network modeling approaches unravel dynamic enhancer-promoter interactions across neural differentiation
Comprehensive network modeling approaches unravel dynamic enhancer-promoter interactions across neural differentiation Open
Background Increasing evidence suggests that a substantial proportion of disease-associated mutations occur in enhancers, regions of non-coding DNA essential to gene regulation. Understanding the structures and mechanisms of regulatory pro…
View article: A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase
A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase Open
Over-activation of the epidermal growth factor receptor (EGFR) is a hallmark of glioblastoma. However, EGFR-targeted therapies have led to minimal clinical response. While delivery of EGFR inhibitors (EGFRis) to the brain constitutes a maj…
AutoEval Done Right: Using Synthetic Data for Model Evaluation Open
The evaluation of machine learning models using human-labeled validation data can be expensive and time-consuming. AI-labeled synthetic data can be used to decrease the number of human annotations required for this purpose in a process cal…