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#单细胞/空间组学

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Sep 28Mon
  1. biorxiv.org54

    Transcriptional networks underlying tumour plasticity in small-cell lung cancer

    Single-cell multi-omics of small-cell lung cancer resolved distinct cell states along the neuroendocrine-to-nonneuroendocrine axis, including a previously unrecognised Intermediate state of low-identity immunogenic cells that serves as an obligatory route in lineage transition. A Boolean Bayes model of transcription factor networks (BoBa-T) predicted state regulators, and RORB was validated as a gatekeeper of the neuroendocrine state: its inactivation pushes NE cells into the Intermediate state, upregulates immunogenic programs, and inhibits tumour growth in immunocompetent hosts.

    Why it matters: Identifies an obligatory immunogenic intermediate state and RORB as a druggable gatekeeper of SCLC lineage plasticity.

  2. biorxiv.org67

    Disruption of the ARID1A-containing SWI/SNF complex reprograms tumor-associated macrophages and enhances immunotherapy response

    Disrupting the SWI/SNF chromatin remodeling complex in tumor-associated macrophages reprograms them and improves checkpoint blockade immunotherapy. Pharmacologic inhibition of SWI/SNF ATPase activity slowed tumor growth, and deleting the SWI/SNF subunit Arid1a in myeloid cells was sufficient to suppress tumor progression and enhance checkpoint blockade response. The reprogramming involved reduced enhancer accessibility at poor-prognosis genes such as Spp1, increased accessibility at interferon-stimulated gene promoters, elevated CD86, and required CD86 costimulation and CD8+ T cells.

    Why it matters: It identifies a druggable epigenetic target in macrophages that improves checkpoint blockade response.

  3. biorxiv.org54

    Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis

    Mosaic structural variants occur in all individuals and germ layers, with long- and short-read WGS of 47 normal tissues (168 samples) showing a median 285.2 kb affected per genome. Most variants were repeat-mediated and 8.3% overlapped functional elements, enriched relative to germline variants. Repeat alterations measured from short reads across 15 cancer types matched normal mosaic variation in scale and enabled tumor tracking in cell-free DNA.

    Why it matters: Quantifies repeat-driven mosaic structural variation in normal tissues and shows repeat changes in cell-free DNA can monitor tumors.

  4. biorxiv.org56

    ctDNA Release Heterogeneity in Luminal Breast Cancer Revealed by Single-Cell Multi-Omics Spatial Analysis

    Eight recurrent malignant epithelial states in non-metastatic HR+/HER2- breast cancer show distinct ctDNA release potential, defined by scMASTER, a framework combining single-cell transcriptomes and mutations, spatial transcriptomics and matched tumor and plasma DNA sequencing across ten patients. Antigen-presentation, stress, mitosis and mesenchymal-like states released most ctDNA, as did EMT-enriched regions, intraductal luminal progenitors and avascular hypoxic zones. PIK3CA and ESR1 mutations tied to distinct functional states altered ctDNA detectability, and a stratification model from these features identified high-risk, immunosuppressed patients with poor prognosis in external cohorts.

    Why it matters: It explains cellular and spatial sources of tissue-plasma discordance that limit liquid biopsy in HR+/HER2- breast cancer.

  5. biorxiv.org47

    Spatial analysis of canine glioma reveals heterogeneous intratumoral niches characterized by distinct patterns of cell plasticity and immunosuppression

    All canine glioma subtypes contain heterogeneous immunosuppressive niches linked to varied epithelial-mesenchymal plasticity (EMP) phenotypes, based on analysis of 30 FFPE cases (10 per subtype). Astrocytomas showed a more-mesenchymal identity tied to tumor-associated macrophage recruitment, while oligodendrogliomas displayed a strong stem-like signature and upregulated a FOXP3/LAG3/SNAI1 triad at the interface of immunosuppression and EMP. The findings support canine glioma as a comparative model for immune checkpoint inhibitor response in human gliomas.

Sep 27Sun
  1. biorxiv.org42

    Integrative Nanopore and Illumina sequencing reveals age-associated tRNA modification and CCA-tail dynamics in yeast

    Nanopore direct RNA sequencing (RNA004 chemistry) with Illumina validation profiles the Saccharomyces cerevisiae tRNAome during replicative aging at single-molecule resolution. Overall tRNA abundance remains largely stable, but aging brings terminal A cleavage at the 3' CCA tail of mature tRNAs, targeted T-loop and anticodon modification changes, and single-molecule evidence of modification co-occurrence. The work adds a benchmarked resource for studying tRNA regulation, translation fidelity, and longevity.

    Why it matters: It links aging to specific tRNA CCA-tail and modification changes at single-molecule resolution.

  2. biorxiv.org62

    A single-nucleus multi-omic atlas of gene regulation across 21 adult human tissues

    A single-nucleus multi-omic atlas maps gene regulation across 21 adult human tissues from four donors, profiling 459,856 nuclei including 160,688 with paired transcriptome and chromatin accessibility. It resolves 313 subclusters and identifies 1,085,062 candidate cis-regulatory elements, 161,270 of them novel, plus 871,177 cCRE-gene links. Trained sequence-to-function models flag 18,133 high-effect fine-mapped variants, giving a framework for interpreting non-coding risk.

    Why it matters: It links regulatory DNA to cell-type-specific expression across 21 tissues and prioritizes fine-mapped non-coding variants.

Sep 26Sat
  1. biorxiv.org48

    SHERLOCK: Structured representation learning and causal inference of downstream perturbation effects

    SHERLOCK is an interpretable deep generative framework that represents genetic, pharmacological, and experimental perturbations as structured interventions on a latent baseline cellular state within a structural causal model. It learns correlated and sparse perturbation representations, organizes perturbations by shared transcriptional responses, and supports counterfactual estimation of downstream transcriptional effects, condition-dependent response analysis, and compositional modeling of combinatorial perturbations. Across genome-scale CRISPR, chemical, and spatial perturbation datasets, it recovers perturbation relationships concordant with known pathways and pharmacological properties and predicts held-out perturbation combinations.

    Why it matters: It unifies perturbation prediction, causal effect estimation, and combinatorial modeling in one framework for single-cell data.

Sep 25Fri
  1. nature.com56

    Single-cell analysis of chromatin accessibility in the human intestine identifies regulatory programs and clarifies genetic associations in Crohn’s disease

    Single-cell ATAC-seq was used to map chromatin accessibility in intestinal mucosa from patients with Crohn's disease and healthy controls. The work characterizes regulatory programs associated with inflammation and genetic effects, clarifying genetic associations in Crohn's disease.

    Why it matters: Links Crohn's disease genetic associations to specific cell-type regulatory programs, aiding interpretation of risk variants.

  2. biorxiv.org42

    Robustness measures for cell type classification in single-cell RNA-seq datasets of kidney organoids

    Two robustness measures, the classification stability score and prediction specificity score, quantify the reliability of cell-type labels from label-transfer tools in scRNA-seq data. Applied to human fetal kidney and four iPSC-derived kidney organoid protocols with a mouse fetal kidney reference, scores were high for most fetal kidney cell types except immature epithelial structures, high for organoid cap mesenchyme, and variable for epithelial lineages depending on protocol. A cell-removal simulation confirmed the measures flag unreliable classifications.

    Why it matters: It gives a practical way to test whether organoid cell-type labels from label transfer are trustworthy.

  3. biorxiv.org51

    A single-nuclei multiomics resource across four brain regions prioritises human neural cell types influencing brain-related traits

    Single-nuclei multiomic profiling of gene expression and chromatin accessibility across ~140,000 nuclei from 40 post-mortem adult brain samples (11 donors, four regions: amygdala, hippocampus, hypothalamus, prefrontal cortex) pinpoints neural cell populations underlying brain-related traits. Integration with GWAS statistics prioritised similar neuronal populations for BMI, schizophrenia, bipolar disorder and age at menarche, and supported enhancer-gene relationships relevant to Alzheimer's disease. The resource nominates effector transcripts and cellular pathways for trait-associated variants.

    Why it matters: It maps non-coding risk variants to specific neural cell types and enhancer-gene pairs across four human brain regions.

  4. biorxiv.org48

    Deconvolution of HIV-1 Mutational Signatures Reveals Dominant and Donor-Specific APOBEC3-Associated Mutagenesis Across Anatomical Compartments

    APOBEC3-associated mutagenesis accounts for roughly half of all HIV-1 mutations across blood, spleen, gut, and brain tissues from 21 people with HIV in the Last Gift rapid autopsy program. Two APOBEC3 signatures were deconvolved from single-genome env DNA sequences, and mutational patterns tracked donor identity rather than anatomical compartment. Identical hypermutated sequences found across brain, gut, and blood indicate clonal expansion and trafficking of infected cells.

    Why it matters: It shows APOBEC3 drives about half of HIV-1 mutations in tissue reservoirs and that mutagenesis is donor-specific.

Sep 24Thu
  1. biorxiv.org45

    CMAC: A deep learning framework for absolute cardiomyocyte transcriptional age estimation

    CMAC, a deep learning framework built from 18 murine single-cell RNA-seq datasets, assigns absolute transcriptional maturation age to cardiomyocytes across platforms and experimental conditions. An XGBoost regressor on its batch-invariant latent space predicted chronological age with leave-one-dataset-out MAE of 4.09 days (Pearson r = 0.903), and in an independent P14 cohort of 98,163 cells achieved mouse-level MAE of 0.33 days. Applied to PGC1/beta double-knockout mice, it quantified maturation deficits of 4.77 to 8.60 days across P7 to P28.

    Why it matters: It provides the first unified way to quantify absolute cardiomyocyte maturation age and deviations from normal development.

  2. biorxiv.org42

    Convergent evolutionary loss of chemosensory and blood-feeding pathways in non-blood-feeding mosquitoes

    Comparing chromosome-level genomes and whole-brain reconstructions across seven mosquito species, including three independent non-blood-feeding lineages, reveals convergent loss of blood-feeding genes: Aegyptin, blood-activated serine proteases Chymotrypsin-1 and 2, a carboxylesterase, and multiple chemosensory receptor clades. Non-blood-feeding females also show reduced female-biased head gene expression and smaller antennal lobes. The work defines a compact gene set underlying a complex trait lost three times over roughly 200 million years.

    Why it matters: Convergent losses across three lineages pinpoint the genes and brain regions required for mosquito blood feeding.

Sep 23Wed
  1. Nature Medicine41

    AI-based characterization of Alzheimer’s disease phenotypes from population-scale single-cell data

    A graph neural network applied to single-cell data from 584 brain donors with Alzheimer's disease and controls identifies differential patterns between disease and control. The model links specific patterns to cognitive resilience and to the insurgence of depression in patients with AD, giving a data-driven way to parse disease phenotypes at single-cell resolution.

    Why it matters: Population-scale single-cell data plus a graph neural network offer an AI route to define Alzheimer's phenotypes.

  2. nature.com56

    Lifespan single-cell transcriptomic atlas of the human prefrontal cortex

    The dorsolateral prefrontal cortex follows non-linear, cell-type-specific transcriptional trajectories across the lifespan, mapped in a single-cell transcriptomic atlas spanning human development through late adulthood. Development shows dynamic remodelling, midlife shows relative stability, and late adulthood shows selective molecular reactivation. The work establishes a lifespan reference for how cortical cell types change with age.

    Why it matters: Provides a lifespan single-cell atlas defining when and which prefrontal cell types change with age.

  3. medrxiv.org55

    Type 2 Deiodinase in Cancer-Associated Fibroblasts: A Potential Therapeutic Target in Many Types of Cancer

    Type 2 deiodinase (DIO2), the enzyme converting T4 to T3, is a conserved marker of cancer-associated fibroblasts (CAF) across thyroid cancer and six additional solid tumor types, and is enriched in myofibroblastic CAF. Elevated DIO2 expression correlated with worse overall survival in pancreatic and bladder cancers, while thyroid cancer showed an inverse association linked to loss of epithelial DIO2 during dedifferentiation. In a TPO-CreERT2/BrafV600E/Trp53-deficient mouse model, Dio2 loss in the tumor microenvironment significantly reduced tumor growth, and D2 activity was suppressed by cefuroxime and lenvatinib.

    Why it matters: Identifies DIO2 as a CAF-restricted, druggable target conserved across solid tumors, with preclinical evidence of tumor suppression.

  4. nature.com57

    Single-nucleus transcriptome-wide association study of human brain disorders

    A single-nucleus transcriptome-wide association study across diverse populations links genetic risk for human brain disorders to specific cell types. The approach reveals previously hidden gene-trait associations and conserved, cell-type-specific mechanisms. It changes how genetic risk for brain disorders can be assigned to the cell types involved.

    Why it matters: It maps genetic risk for brain disorders to specific cell types, adding cell-type resolution to gene-trait associations.

Sep 16Wed
  1. Sci Adv68

    Fluorescent protein ticker tape (FPTT): Multiplexed recording of transcriptional dynamics in living cells and in vivo.

    Fluorescent protein ticker tapes (FPTT) record multiple transcriptional histories in single living cells by combining multispectral fluorescent proteins with self-assembling protein fibers. FPTT logged dose-dependent, reversible endogenous cFos transcription in hippocampal neurons at 3-hour resolution over 8 days, and variants were engineered for NF-κB, STAT3, mTOR, NFAT and cAMP signaling, enabling simultaneous analysis of four pathways during T cell activation. The tool revealed NFAT/STAT3 cross-talk and cell cycle-dependent mTOR oscillations.

    Why it matters: It delivers a scalable method for multiplexed, longitudinal recording of transcriptional dynamics in living cells and in vivo.

  2. Cancer Cell57

    Latent tumor killers awakened.

    A single-cell atlas of bone marrow T cells from patients with bone marrow-resident malignancies reveals tumor-reactive populations in a state of latent competence. A 15-gene signature identifies this subset, which is expanded by immunotherapies and predicts clinical responses. The work pinpoints a definable T cell state that clinicians could use to gauge who will respond to immunotherapy.

    Why it matters: A 15-gene signature of latent tumor-reactive T cells may predict immunotherapy response in marrow-resident cancers.

Sep 15Tue
  1. Nat Biotechnol44

    Detecting and quantifying circular RNAs in terabyte-scale RNA-seq datasets with CIRI3.

    CIRI3 detects and quantifies circular RNAs in terabyte-scale RNA-seq datasets, running an order of magnitude faster than existing tools with increased accuracy through dynamic multithreaded task partitioning and a blocking search strategy for junction reads. Applied to 2,535 cancer-related samples, it identified differentially spliced circRNAs and yielded the CIRIonco database with a pretraining model and biomarker network.

    Why it matters: A much faster and more accurate tool makes large-scale circRNA analysis across cancer datasets practical.

Sep 14Mon
  1. Sci Adv48

    Widespread atypical UV-induced mutations form in single-stranded DNA.

    UV light induces an extended array of noncanonical mutations in single-stranded DNA, including AT>AM, GT>GV, AC>AA, AT>TT, and TA>TT substitutions that resist photo-reversion and likely originate from atypical photoproducts. The work coupled temperature-induced telomeric end resection in yeast with serial UV irradiation and whole-genome sequencing. These ssDNA-specific lesions offer an additional damage-mediated route to oncogenic melanoma mutations such as BRAF V600E, which involves a GT>GA substitution.

    Why it matters: It explains how UV light can generate melanoma-driver mutations that canonical SBS7-type lesions do not account for.

Sep 11Fri
  1. Cell49

    Architecture of the serotonergic projectome in the mouse brain.

    The serotonergic projectome in the mouse brain is organized by functional relatedness of target regions rather than their physical proximity. Whole-brain axon tracing shows dorsal and median raphe serotonin neurons fall into five projectomic groups, each preferentially innervating the hippocampus, basal ganglia, cortex, medial interbrain, or brainstem/lateral thalamus. Spatial transcriptomics links each group to distinct transcriptomic clusters, and projection-specific serotonin depletion yields dissociable behavioral phenotypes.

    Why it matters: It maps the full serotonin projection architecture and ties it to transcriptomics and behavior, reframing how serotonin modulation is organized.

Sep 10Thu
  1. medrxiv.org71

    A spatial single-cell transcriptomic atlas of metastatic breast cancer progression

    A single-cell spatial transcriptomic atlas of metastatic breast cancer profiles 520,850 cells from 126 tumor samples of 44 patients, covering 171,766 cancer cells and 349,084 tumor microenvironment cells across primary and metastatic lesions. Multiple time points per patient revealed treatment-induced transcriptional changes driving therapy resistance, immune subpopulations predictive of hormone receptor loss, and transcriptomic features of subclones selected during progression that hold future metastatic potential.

    Why it matters: It provides a large longitudinal spatial single-cell resource for studying metastatic breast cancer progression and therapy resistance.

  2. Nature69

    Cell-type signatures of Alzheimer's disease shared across population groups.

    Cell-type signatures of Alzheimer's disease are shared across Latin, white and African American population groups. Single-nucleus RNA sequencing and ATAC-seq of post-mortem cortical and subcortical brain tissue identified disease-associated microglial, astrocytic and neuronal clusters in all three groups, plus continuous gene-expression factors in astrocytes and oligodendrocytes. Molecular programs defined six subgroups of individuals with cognitive impairment that span all three populations and are not captured by neuropathology.

    Why it matters: Representative multi-population sampling shows which Alzheimer's cell-type signatures are shared and reveals molecularly defined disease subgroups.

Sep 9Wed
  1. Nat Biotechnol63

    Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors.

    Light-sheet live imaging of late-stage preimplantation human embryos, enabled by mRNA electroporation of nuclear DNA labels, shows chromosome segregation errors arising de novo immediately before implantation, including multipolar spindles, lagging chromosomes, misalignment and mitotic slippage. Most lagging chromosomes are passively inherited rather than reincorporated, and most labeled cells remain externally positioned, consistent with placental fate. The findings question clinical uses of preimplantation genetic testing for aneuploidy.

    Why it matters: Direct imaging shows aneuploidy can arise after fertilization at late preimplantation stages, questioning PGT-A interpretation.

Sep 8Tue
  1. Science45

    Thalamic NRXN1-mediated input to human cortical progenitors drives excitatory neurogenesis.

    Thalamic input increases production of cortical excitatory neurons during human cortical development, according to fused cortical and thalamic organoids analyzed by single-nuclei RNA-sequencing and cellular imaging. Neurexin-1 (NRXN1) mediates physical contact between thalamic axons and cortical outer radial glia; genetic knockout of thalamic NRXN1 reduced these contacts and attenuated production of upper-layer excitatory neurons. The work identifies a thalamic mechanism controlling human cortical progenitors.

    Why it matters: It identifies NRXN1 as a molecular link by which thalamic axons regulate human excitatory neurogenesis.

Sep 6Sun
  1. Cell53

    Four-dimensional molecular mapping from a spatial snapshot reveals the dynamics of hair follicle organogenesis.

    A spatial transcriptomics method called 3D DNase-Enhanced Expression Profiling captures gene expression hundreds of microns deep in cleared intact tissue, and applied to neonatal mouse skin it mapped hundreds of developing hair follicles in 3D. Ordering follicles by molecularly inferred developmental age turned one snapshot into a four-dimensional map of organogenesis, revealing stem cell compartment stratification, new cell subtypes, and hair canal formation. In Foxn1-deficient nude mice, organ-wide delays and reduced coordination appeared before overt structural defects.

    Why it matters: It converts a single spatial snapshot into a time-resolved 3D molecular map of organ formation.

Sep 4Fri
  1. Mol Cell47

    Molecular co-accessibility identifies coordinated regulation between distant cis-regulatory elements.

    Single-molecule footprinting combined with long-read sequencing across Drosophila cis-regulatory landscapes shows that cis-regulatory elements form networks with shared single-molecule chromatin accessibility profiles. Co-accessibility often occurs between distant elements brought together by chromatin looping, and co-accessible elements show strong coordination in cell-type-specific accessibility. The findings support coordinated enhancer activation as a widespread gene-regulatory mechanism.

Sep 3Thu
  1. Mol Cell49

    A conserved mechanism of membrane fusion in nuclear pore complex assembly.

    Brl1 and Brr6 mediate fusion of the inner and outer nuclear membranes during nuclear pore complex assembly in S. cerevisiae, forming ring-shaped complexes with membrane-remodeling activity; Brl1 reaches assembly sites via a nuclear export sequence and interacts with Brr6 through conserved hydrophobic loops, and disrupting this interaction blocks fusion and halts NPC assembly. Molecular dynamics simulations indicate the Brl1-Brr6 complex forms a channel across the bilayers enabling lipid exchange, and phylogenetic and functional work identifies CLCC1 as the NPC fusogen in metazoans, including human cells and D. melanogaster.

  2. Cell44

    Tabula Sapiens 2.0: A comprehensive transcriptomic atlas of human cell types.

    Tabula Sapiens 2.0 expands the human cell atlas with data from nine new donors, doubling the number of cells and adding four new tissues. Four donors contributed multiple organs, giving a dataset in which genetic background, age, and epigenetic effects are controlled for. The atlas contains transcripts from nearly all human transcription factors, enabling putative cell-type specificity for nearly every one, and its senescence-gene analyses reveal the context-dependent heterogeneity of cellular senescence.

  3. Nature69

    Cell-type-specific eQTLs underlie the genetic architecture of complex traits.

    Cell-type-specific eQTLs, mapped with a variance component model applied to population-scale single-cell RNA-seq of peripheral blood mononuclear cells from the OneK1K cohort, enrich for complex trait heritability, unlike cell-type-shared eQTLs. Trans eQTLs were mostly cell-type-specific (60%) while cis eQTLs were mostly shared (30% specific). Findings, replicated in a second dataset across ancestries, explain partly why known eQTLs are depleted in gene regulatory effects on complex traits.

    Why it matters: Shows why known eQTLs miss complex-trait heritability: specificity to cell type, not eQTLs overall, carries the signal.

  4. Nature47

    Robust inference and correlates from genetic associations with personality.

    A meta-analysis of up to 1.14 million participants across 46 cohorts identifies 1,260 lead genetic variants for Big Five personality traits, 824 of them novel. Common variants explain 4.8-9.3% of variance per trait, rising to 9.3-13.3% for instruments with typical reliability. Within-family GWAS in up to 50,725 participants show these associations are minimally confounded by shared family environment, and polygenic prediction, genetic correlation and Mendelian randomization point to potentially causal links with life outcomes.

Sep 2Wed
  1. Cell49

    De novo pan-rhodamine binders for fluorescence microscopy from mammalian cells to extremophiles.

    De novo designed rhodamine binders (Rhobin) create a single tagging system combining high brightness, reversible binding, compact size, and stability. Rhobin surpasses existing tags in brightness in live- and fixed-cell mammalian imaging, supports STED and extended live-cell single-molecule imaging compared with HaloTag, and enables live imaging of Sulfolobus acidocaldarius at 75°C, previously inaccessible with current tags.

  2. Cell52

    Cross-species single-cell atlas of the striatum defines cell-type and subregion disease vulnerabilities.

    A cross-species single-nucleus RNA sequencing atlas of the striatum, built from 109 human and 22 mouse samples spanning dorsal and ventral striatum, maps subregional neuronal specialization along the dorsolateral-ventromedial axis and defines rare neuronal subpopulations with notable differences between species. Integration with genome-wide association and pharmacological studies identifies human-enriched opioid receptor expression sites and ventral-biased chronic antipsychotic action, while paired transcriptomic and repeat expansion measurements pinpoint subregion and neuronal subtype vulnerability in Huntington's disease.

  3. Cell51

    Live-cell transcriptomics with engineered virus-like particles.

    Engineered mammalian cells can now self-report their transcriptional states by exporting mRNA in virus-like particles, allowing repeated sampling of culture media instead of lysing cells. The approach captured evolving transcriptional states during inflammatory stimulation of primary cell spheroids and multi-day pluripotent stem cell differentiation, and enabled selective longitudinal tracking of endothelial cell dynamics in a microphysiological co-culture system to identify perivascular stroma-dependent gene programs underlying vasculogenesis. It establishes live-cell transcriptome-wide profiling in the same sample over time.

Sep 1Tue
  1. Nature60

    Ultrafast and reference-free sequence discovery in single-cell data.

    Malva is a computational platform that lets researchers search raw sequence space across single-cell and spatial transcriptomics data without a reference genome, at species-agnostic scale. Its expanding index already covers about 74 million cells from thousands of experiments in health and disease, supporting searches for any sequence, mutation, splice junction or pathogen, and reference-free cell type identification. It turns single-cell atlases from static gene count tables into dynamic, sequence-resolved resources.

    Why it matters: It makes petabyte-scale raw single-cell sequence data searchable without references or downloads.

  2. Nat Biotechnol50

    Bonsai reconstructs tree representations for distortion-free visualization and exploration of high-dimensional data.

    Bonsai reconstructs the most likely tree relating high-dimensional objects with heterogeneous measurement noise, automatically regularizing noise, recovering differentiation trajectories, preserving high-dimensional distances, and improving nearest-neighbor identification. Applied to blood cell data, it recovers known lineage relationships and discovers a natural killer cell subtype deriving from the myeloid lineage, pinpointing genes that distinguish myeloid NK from lymphoid NK cells. It requires no tunable parameters and scales to large datasets.

Aug 29Sat
  1. Cell70

    Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits.

    A genome-scale perturb-seq platform perturbed all expressed genes across 22 million primary human CD4+ T cells from four donors, measuring transcriptome effects at rest and after stimulation. The resulting maps identify regulators of immune pathways, including previously uncharacterized regulators of cytokine production, and show that active regulators and the programs they control change dramatically across stimulation conditions. The signatures nominate regulators of T cell polarization, age-related phenotypes, and context-specific pathways in autoimmune disease risk.

    Why it matters: It maps context-specific gene regulators in primary human CD4+ T cells and links them to immune traits and autoimmune disease risk.

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