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Methods & resources

New techniques, tools, datasets and atlases — and methodological finds that discount prior data.

184 picksRelatedSingle-cell & spatial omicsAI drug discoveryPrimary research

Latest picks

21–40 of 184
Oct 15Thu
  1. Cell79

    An opioid efficacy switch for reversible optical control of analgesia

    Azo-morphine-3 (AM-3) is a photoswitchable ligand that toggles mu-opioid receptor activity between low and high efficacy states, working in vitro and in vivo in both brain and periphery. Light-driven switching gave spatiotemporally precise control of analgesia across pain models with reduced side effects compared with systemic drugs. It also serves as a tool to probe the structural basis of opioid efficacy.

    Why it matters: It offers reversible optical control of opioid analgesia with fewer side effects than systemic drugs.

  2. Nature72

    Structural variant detection across sequencing technologies

    HitSV, a read-length-agnostic structural variant (SV) calling approach, models how local genomic repetitiveness distorts alignment signatures and combines progressive clustering with haplotype-resolved local assembly for SV reconstruction. Applied to long-read, short-read and hybrid data, it achieved high yields across sequencing technologies, reduced long-read sequencing data requirements, and maximized SV discovery from short-read data. Applied to a large-scale Chinese cohort, it identified composite repeat architectures featuring tandem-mobile-element arrays as a pervasive, previously underrecognized feature of human genomes.

    Why it matters: It improves structural variant detection across short-read, long-read and hybrid data and reveals underrecognized composite repeat architecture in human genomes.

  3. Nature71

    Artificial intelligence-enabled clinical phenotyping of human brown fat

    AI-enabled quantification of brown adipose tissue (BAT) activity in humans links higher BAT activity to a healthier metabolic profile and lower rates of psychiatric disease. The same approach identified existing pharmacologic agents that could be repurposed to activate BAT in humans. The work provides a scalable way to phenotype BAT and connect it to clinical outcomes and drug targets.

    Why it matters: It shows AI-based BAT phenotyping at scale, linking brown fat to metabolic and psychiatric outcomes and to repurposable drugs.

  4. Nature80

    Computational design of metalloproteases

    RFdiffusion was used to design proteins de novo with water-activating zinc-based active sites positioned next to a peptide substrate binding pocket. The resulting proteases were highly active and programmable, with the authors pointing to potential applications in therapeutics, biotechnology and bioremediation.

    Why it matters: De novo design of active, programmable metalloproteases extends computational protein design to catalysis.

  5. Nature80

    Modelling mouse embryogenesis from chemically induced totipotent stem cells

    A research team built a mouse embryo model from chemically induced totipotent-like stem cells. The model progressed sequentially through key developmental stages: gastrulation, embryonic axis formation, haematopoiesis and early organogenesis. Original title: Modelling mouse embryogenesis from chemically induced totipotent stem cells. DOI: 10.1038/s41586-026-11164-5.

    Why it matters: The model recapitulates key developmental milestones from gastrulation to early organogenesis, offering an in vitro alternative to natural embryos for studying early mammalian development.

Oct 14Wed
  1. 顶刊论文（社媒热度）71

    MAGIC: an international network for evaluating generative artificial intelligence in global health.

    The authors establish MAGIC, an international network for evaluating generative artificial intelligence in global health. The network brings together collaborators across institutions in Asia, Europe, Africa and the Americas, including groups at Duke-NUS Medical School, Harvard, Tsinghua and the World Health Organization Regional Office for South-East Asia, with a focus on the ethics, regulation and standardization of AI for health.

    Why it matters: Sets out an international framework for evaluating generative AI in global health, relevant to clinicians and researchers deploying these tools.

  2. Nature Biotechnology82

    In vivo engineering of CAR natural killer cells for immunotherapy using ligand-directed lipid nanoparticles.

    Ligand-directed lipid nanoparticles (NtLNPs) carrying mRNA transfected up to ~80% of NK cells in vivo in mice with minimal off-target effects, generating CAR NK cells without ex vivo engineering. CD19-targeted CAR NKs completely depleted circulating B cells in healthy mice, CD3-targeted CAR NKs eliminated nearly all autoreactive T cells in autoimmune hepatitis, and NKG2A-targeting versions improved solid tumor efficacy. Human-optimized NtLNPs produced CAR NK cells that regressed two humanized hematologic malignancy models. The work replaces viral, ex vivo CAR manufacturing with a modular in vivo mRNA delivery platform.

    Why it matters: It shows nonviral in vivo CAR NK generation, a route around ex vivo viral engineering of cell therapies.

  3. YouTube73

    Deisseroth Traces the History of Optogenetics From Microbial Opsins to Precise Neuron Control

    iBiology Science Stories has released a 21-minute lecture by Deisseroth reviewing the methodological history of optogenetics. He traces the field's key milestones from the discovery of microbial opsins to the precise control of neurons.

    Why it matters: It lays out the key milestones of optogenetics from microbial opsin discovery to precise neuron control, showing readers how the method developed and who contributed.

  4. YouTube76

    HHMI Janelia Releases CellposeSAM, a Cell Segmentation Foundation Model Combining SAM Encoder with Cellpose Flow Fields

    HHMI Janelia has released CellposeSAM, a foundation model for cell segmentation. It replaces the original UNet with the SAM image encoder (256×256, 8×8 patches, global attention at all layers) to predict cell flow fields, and masks are obtained by gradient tracking.

    Why it matters: The source gives the concrete architecture and benchmark data for combining the SAM visual encoder with Cellpose flow fields, which readers can directly transfer to their own segmentation tasks for comparison.

Oct 13Tue
  1. WeChat67

    Shotgun Genetic Engineering Enables CHO Cells to Synthesize Valine and Isoleucine Autonomously

    Nature Biotechnology reports a shotgun genetic engineering (SGE) method that screens millions of synthetic metabolic pathway combinations in parallel, enabling CHO cells to efficiently synthesize valine on their own and establishing isoleucine biosynthesis capability in mammalian cells. The work provides a new engineering paradigm for mammalian metabolic pathway engineering.

    Why it matters: Shotgun genetic engineering screens millions of metabolic pathway combinations in parallel in CHO cells, offering a transferable high-throughput paradigm for mammalian metabolic engineering.

  2. Nature Biotechnology72

    Discovery and engineering of retrons for precise genome editing.

    Engineered retron reverse transcriptases identified from metagenomic data produce single-stranded DNA donors in mammalian cells at efficiencies comparable to conventional oligodeoxynucleotide donors, but from a genetically encoded cassette. The editors work with Cas12a nuclease and Cas9 nickase, broadening targetable sites and avoiding double-stranded breaks. An all-RNA delivery strategy enables DNA-free editing in cells and vertebrate embryos, demonstrated by inserting a split GFP epitope tag for live-cell imaging.

    Why it matters: It turns retrons into genetically encoded donor systems for precise editing without exogenous DNA or double-strand breaks.

  3. 顶刊论文（社媒热度）61

    MIMAS: An open-source microlens-array miniature microscope for accessible large-field cortical imaging in freely behaving mice.

    An open-source head-mounted fluorescence microscope using a 4 × 5 microlens array as its sole imaging element achieves cellular-resolution imaging over an approximately 4 × 4.5 mm2 field of view at 2.31 g. In freely behaving mice, it captured calcium signals from thousands of layer 2/3 neurons across multiple dorsal cortical regions, plus wide-field vascular imaging with vessel caliber-dependent hemodynamic responses to isoflurane. It offers labs a low-complexity route to large-scale cortical imaging.

    Why it matters: Open-source single-array optics put cellular-resolution wide-field cortical imaging within reach of ordinary labs.

  4. YouTube72

    Janelia Reports Cell Observatory Plan Combining Lattice Light Sheet and Adaptive Optics for Non-Perturbing Subcellular Imaging

    Eric Betzig reported at Janelia on progress in the Cell Observatory initiative, arguing for tools such as lattice light sheet microscopy, PALM, SIM and adaptive optics to observe subcellular dynamics in multicellular systems without perturbation. The talk described using a light sheet with an SLM to achieve 3-phase/5-phase SIM, pushing resolution to about 130 nm, and single-objective inverted light sheet microscopy for 'fish brain' imaging.

    Why it matters: Janelia integrates lattice light sheet, PALM, SIM and adaptive optics into a non-perturbing imaging platform for subcellular dynamics in multicellular systems.

Oct 12Mon
  1. 文献与产业新闻40

    Modelling nano-particle-PEG-NLS complexes for nucleus-targeted drug delivery: revisiting the multi-dynein nano-cargo transport on microtubules

    Researchers developed an energy-based enhanced simulation of nanoparticles hauled along microtubules toward the nuclear envelope by multiple dynein motors via flexible PEG-NLS linkers. The model reproduces the decrease in longitudinal velocity with dynein number and the accompanying rise in run distance and run time, falling within the 95% confidence intervals of recent motility experiments for 1 to 6 mean bound dyneins. A scan of a 20 nm radius, six-dynein system shows run time and distance are optimal at a linker contour length of about 40 nm.

    Why it matters: Simulation offers quantitative design rules for nucleus-targeted nanoparticle drug delivery.

  2. WeChat67

    Nature Paper Maps Spatial Proteome of Human Body and Cancers Across 2856 Clinical Samples

    A Nature paper maps spatial proteome distribution across the human body and cancers, built from 2856 clinical specimens analyzed by DIA-MS and covering more than 13,000 proteins. The dataset spans 58 major tissue types, 251 tissue subtypes and 25 cancers, and traces proteome trajectories across physiological states including fetal, tumor, adjacent non-tumor and healthy adult tissue.

    Why it matters: It provides a large open clinical proteomics resource for cross-tissue and cancer comparison.

Oct 11Sun
  1. bioRxiv40

    BoNTax: a curated genome-based framework for taxonomic classification and characterization of Clostridium botulinum Group I and Clostridium sporogenes

    BoNTax decouples ANI-based species assignment from botulinum neurotoxin characterization for Clostridium botulinum Group I and Clostridium sporogenes. Analysis of 966 genomes informed selection of 46 references that resolved into two species clusters with within-species ANI >95% and between-species ANI <95%, supporting a 95% species threshold. Of 42 validation genomes, 29 of 32 reported assignments were concordant, three prompted re-evaluation, and ten unknown genomes received ANI-based assignments. BoNT typing, including bivalent strains, was fully concordant.

    Why it matters: Gives public-health labs a standardized GalaxyTrakr workflow that separates species identity from toxin genotype in closely related clostridia.

  2. 顶刊论文（社媒热度）66

    Contagion-preserving compression for multiscale epidemic modeling.

    Iterative structural coarse-graining (ISCG) compresses large networks into multiscale representations that preserve contagion dynamics. In the saturation regime the compressed networks reproduce outbreak sizes, node-level infection risks, and spatiotemporal infection trajectories. Interventions designed on these representations, including influence maximization, immunization, and surveillance, consistently outperform adaptive centrality-based methods.

    Why it matters: Offers a compression method that preserves contagion dynamics and improves intervention design on large networks.

  3. WeChat64

    ULTRA Delivers Three-Dimensional Intraoperative Pathology in 30 Minutes to Map Glioma Boundaries

    A technique called ULTRA produces three-dimensional pathology of brain tissue in about 30 minutes, fast enough for use during glioma surgery. Diffuse glioma cells infiltrate normal brain beyond what visual inspection and MRI can identify, and earlier 3D histology methods took hours to days because of labeling, staining and repeated imaging, ruling out intraoperative use. ULTRA is intended to identify the infiltrating tumor boundary during the operation.

    Why it matters: It cuts intraoperative 3D histology from hours or days to 30 minutes for glioma margin detection.

Oct 10Sat
  1. Cell76

    Mapping transcriptional responses to cellular perturbations with RNA fingerprinting.

    RNA fingerprinting maps transcriptional responses from new single-cell experiments onto reference perturbation dictionaries, assigning query cells probabilistically to one or more candidate perturbations. Benchmarks on ground-truth datasets show accurate single-cell assignments, scalability to genome-wide screens, and resolution of combinatorial perturbations. Applications include identifying p53 regulators under ribosomal stress, dose-dependent drug mechanisms of action, and cytokine-driven B cell heterogeneity in secondary influenza infection in vivo.

    Why it matters: It provides a framework for causal interpretation of single-cell data by matching cellular states to perturbations.

  2. AI × 生物医药40

    Learning Probabilistic Logic Programs with Functional Gradient Guided Language Models

    grasp (Gradient-boosted Synthesis of Probabilistic logic programs) learns probabilistic logic programs by treating relational structure learning as functional gradient boosting, with first-order rules as weak learners and an LLM serving as the proposal oracle for the inner search. Across four relational benchmarks, including molecular toxicity prediction (Tox21), mutagenesis, and citation matching (Cora), grasp improves over purely symbolic, neural, and LLM-based baselines while yielding interpretable weighted rule ensembles and retaining boosting guarantees.

    Why it matters: It shows LLM-guided boosting can synthesize interpretable logic programs that beat symbolic, neural, and LLM baselines on molecular benchmarks.

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org