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 2023 papers, sorted by Most cited.
Self-Refine: Iterative Refinement with Self-Feedback
Like humans, large language models (LLMs) do not always generate the best output on their first try. Motivated by how humans refine their written text, we introduce Self-Refine, an approach for improving initial outputs from LLMs through iterative feedback and refinement. The main idea is to generate an initial output using an LLMs; then, the same LLMs provi…
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
The mammalian brain consists of millions to billions of cells that are organized into many cell types with specific spatial distribution patterns and structural and functional properties<sup>1-3</sup>. Here we report a comprehensive and high-resolution transcriptomic and spatial cell-type atlas for the whole adult mouse brain. The cell-type atlas was created…
Fast and sensitive GCaMP calcium indicators for imaging neural populations
Calcium imaging with protein-based indicators<sup>1,2</sup> is widely used to follow neural activity in intact nervous systems, but current protein sensors report neural activity at timescales much slower than electrical signalling and are limited by trade-offs between sensitivity and kinetics. Here we used large-scale screening and structure-guided mutagene…
Transcriptomic diversity of cell types across the adult human brain
The human brain directs complex behaviors, ranging from fine motor skills to abstract intelligence, but the diversity of cell types that support these skills has not been fully described. In this work, we used single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain. We sampled more than three million nuclei from appro…
Molecularly defined and spatially resolved cell atlas of the whole mouse brain
In mammalian brains, millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells have impeded our understanding of the molecular and cellular basis of brain function. Recent advances in spatially resolved single-cell transcriptomics have enabled systematic map…
Predicting cellular responses to complex perturbations in high‐throughput screens
Recent advances in multiplexed single-cell transcriptomics experiments facilitate the high-throughput study of drug and genetic perturbations. However, an exhaustive exploration of the combinatorial perturbation space is experimentally unfeasible. Therefore, computational methods are needed to predict, interpret, and prioritize perturbations. Here, we presen…
Pluripotent stem cell-derived model of the post-implantation human embryo
The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Models of the embryo derived from stem cells are important tools for interrogating developmental events and tissue-tissue crosstalk during these stages1. Here we es…
Transcriptomic cytoarchitecture reveals principles of human neocortex organization
Variation in cytoarchitecture is the basis for the histological definition of cortical areas. We used single cell transcriptomics and performed cellular characterization of the human cortex to better understand cortical areal specialization. Single-nucleus RNA-sequencing of 8 areas spanning cortical structural variation showed a highly consistent cellular ma…
Comparative transcriptomics reveals human-specific cortical features
The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets to understand human-specific features of t…
A membrane-associated MHC-I inhibitory axis for cancer immune evasion.
Immune-checkpoint blockade has revolutionized cancer treatment, but some cancers, such as acute myeloid leukemia (AML), do not respond or develop resistance. A potential mode of resistance is immune evasion of T cell immunity involving aberrant major histocompatibility complex class I (MHC-I) antigen presentation (AP). To map such mechanisms of resistance, w…
Glioma synapses recruit mechanisms of adaptive plasticity.
The role of the nervous system in the regulation of cancer is increasingly appreciated. In gliomas, neuronal activity drives tumour progression through paracrine signalling factors such as neuroligin-3 and brain-derived neurotrophic factor1-3 (BDNF), and also through electrophysiologically functional neuron-to-glioma synapses mediated by AMPA (α-amino-3-hydr…
A comparative atlas of single-cell chromatin accessibility in the human brain
Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.…
Single-cell DNA methylation and 3D genome architecture in the human brain
Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in 517 thousand cells (399 thousand neurons and 118 thousand non-neurons) fr…
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
The mammalian brain is composed of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. Here, we report a comprehensive and hi…
Integrated intracellular organization and its variations in human iPS cells
Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challenge owing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behaviours that they determine<sup>1,2</sup>. Here we reduced this complexity by focusing on cellular organization-a key readout and driver of cell behaviour<s…
RL4F: Generating Natural Language Feedback with Reinforcement Learning for Repairing Model Outputs
Despite their unprecedented success, even the largest language models make mistakes.Similar to how humans learn and improve using feedback, previous work proposed providing language models with natural language feedback to guide them in repairing their outputs. Because human-generated critiques are expensive to obtain, researchers have devised learned critiq…
Sensitivity optimization of a rhodopsin-based fluorescent voltage indicator
The ability to optically image cellular transmembrane voltages at millisecond-timescale resolutions can offer unprecedented insight into the function of living brains in behaving animals. Here, we present a point mutation that increases the sensitivity of Ace2 opsin-based voltage indicators. We use the mutation to develop Voltron2, an improved chemigeneic vo…
Single-cell DNA methylome and 3D multi-omic atlas of the adult mouse brain
Cytosine DNA methylation is essential in brain development and is implicated in various neurological disorders. Understanding DNA methylation diversity across the entire brain in a spatial context is fundamental for a complete molecular atlas of brain cell types and their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3…
Persistent serum protein signatures define an inflammatory subcategory of long COVID
Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute SARS-CoV-2 infection. The aetiologies may include persistent inflammation, unresolved tissue damage or delayed clearance of viral protein or RNA, but the biological differences they represent are not fully under…
Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex
Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to r…