Paper corpus
The substrate's largest content table — every paper carries an abstract, journal · year, citation count, MeSH terms, and outbound links to PubMed, DOI, and PMC where available.
Showing 2024 papers, sorted by Most cited.
How to build the virtual cell with artificial intelligence: Priorities and opportunities
Cells are essential to understanding health and disease, yet traditional models fall short of modeling and simulating their function and behavior. Advances in AI and omics offer groundbreaking opportunities to create an AI virtual cell (AIVC), a multi-scale, multi-modal large-neural-network-based model that can represent and simulate the behavior of molecule…
Principles and therapeutic applications of adaptive immunity
Adaptive immunity provides protection against infectious and malignant diseases. These effects are mediated by lymphocytes that sense and respond with targeted precision to perturbations induced by pathogens and tissue damage. Here, we review key principles underlying adaptive immunity orchestrated by distinct T cell and B cell populations and their extensio…
Integrated multimodal cell atlas of Alzheimer’s disease
Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 dono…
A single-cell time-lapse of mouse prenatal development from gastrula to birth
The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans1,2. Mouse gestation lasts only 3 weeks, during which the genome orchestrates the astonishing transformation of a single-cell zygote into a free-living pup composed of more than 500 million cells. Here, to establish a global…
Single-cell genomics and regulatory networks for 388 human brains
Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For…
Brain-wide neural activity underlying memory-guided movement
Behavior relies on activity in structured neural circuits that are distributed across the brain, but most experiments probe neurons in a single area at a time. Using multiple Neuropixels probes, we recorded from multi-regional loops connected to the anterior lateral motor cortex (ALM), a circuit node mediating memory-guided directional licking. Neurons encod…
Deciphering the impact of genomic variation on function
Our genomes influence nearly every aspect of human biology-from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development…
Neural circuit basis of placebo pain relief
Placebo effects are notable demonstrations of mind-body interactions<sup>1,2</sup>. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain-a phenomenon known as placebo analgesia<sup>3-6</sup>. However, despite the strength of placebo effects and their impact on everyday human experience and t…
Chromatin context-dependent regulation and epigenetic manipulation of prime editing
We set out to exhaustively characterize the impact of the cis-chromatin environment on prime editing, a precise genome engineering tool. Using a highly sensitive method for mapping the genomic locations of randomly integrated reporters, we discover massive position effects, exemplified by editing efficiencies ranging from ∼0% to 94% for an identical target s…
Changes in Alzheimer Disease Blood Biomarkers and Associations With Incident All-Cause Dementia.
IMPORTANCE: Plasma biomarkers show promise for identifying Alzheimer disease (AD) neuropathology and neurodegeneration, but additional examination among diverse populations and throughout the life course is needed. OBJECTIVE: To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dw…
Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years
Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools an…
Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies
Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cascades. To enable systematic exploration of how receptor valency and geometry affect signaling outcomes, we designed cycli…
Measurement of circulating viral antigens post-SARS-CoV-2 infection in a multicohort study
OBJECTIVES To determine the proportion of individuals with detectable antigen in plasma or serum after SARS-CoV-2 infection and the association of antigen detection with postacute sequelae of COVID-19 (PASC) symptoms. METHODS Plasma and serum samples were collected from adults participating in four independent studies at different time points, ranging from s…
Symbolic recording of signalling and cis-regulatory element activity to DNA
Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction or live imaging of a biological sample within the timeframe of interest. Here we demonstrate an alternative paradigm in which such biological activities are stably recorded to the genome. Enhancer-driven genomic recor…
Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision
The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8+ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics, q…
GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant
Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror sp…
Interleukin-4 downregulates transcription factor BCL6 to promote memory B cell selection in germinal centers
Germinal center (GC)-derived memory B cells (MBCs) are critical for humoral immunity as they differentiate into protective antibody-secreting cells during re-infection. GC formation and cellular interactions within the GC have been studied in detail, yet the exact signals that allow for the selection and exit of MBCs are not understood. Here, we showed that…
Multiplex profiling of developmental cis-regulatory elements with quantitative single-cell expression reporters
The inability to scalably and precisely measure the activity of developmental cis-regulatory elements (CREs) in multicellular systems is a bottleneck in genomics. Here we develop a dual RNA cassette that decouples the detection and quantification tasks inherent to multiplex single-cell reporter assays. The resulting measurement of reporter expression is accu…
Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements
CRISPR-based gene activation (CRISPRa) is a strategy for upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive cis-regulato…
In search of verifiability: Explanations rarely enable complementary performance in AI‐advised decision making
Abstract The current literature on AI‐advised decision making—involving explainable AI systems advising human decision makers—presents a series of inconclusive and confounding results. To synthesize these findings, we propose a simple theory that elucidates the frequent failure of AI explanations to engender appropriate reliance and complementary decision ma…