Investigations of G protein-coupled receptors (GPCRs) interactions with non-visual arrestins in living cells are essential to understanding the complex molecular mechanisms of GPCR-based signaling. Quantitative analysis of these interactions remains challenging in live cells, particularly when attempting to repeatedly image distinct cellular regions with high precision. Here, we describe the implementation of an optical imaging […]
Mapping breast cancer lineage in radiation and immunotherapy using the REMAP mouse
We present REMAP (Recording Evolution in Mammary tumors via Active PyMT), a lineage-tracing mouse model that integrates inducible CRISPR recording with the MMTV-PyMT model of hormone receptor-positive (HR+) breast cancer. Inducible Cas9 drives editing of MARC1 homing guide RNAs (hgRNAs), generating heritable lineage marks, and enables reconstruction of clonal relationships. Using REMAP, we profiled tumor […]
The role of space in explaining macroecological patterns of microbial abundance
Understanding the origin of universal macroecological patterns in microbial communities remains a central open question in ecology. A key observation is that species abundance fluctuations across diverse biomes are well described by a gamma distribution, yet the mechanism responsible for this regularity is debated. Prevailing explanations invoke exogenous stochastic forcing, while endogenous interaction-based approaches—grounded in […]
Defining the DNA Binding Specificity of GRHL2
Grainyhead-like 2 (GRHL2) is an epithelial transcription factor with context-dependent regulatory roles, yet the sequence rules governing its DNA recognition remain incompletely defined. In this study, a high-density genomic Specificity and Affinity for Protein (SNAP) DNA-binding array containing 772,732 tiled probes derived from GRHL2 ChIP-seq regions was used to resolve GRHL2 binding specificity at 6 […]
Coordinated Tuning of Ionizable Lipids and Formulation Redirects mRNA Vaccines Toward Lymphoid-Specific CD4+ T Cell Immunity
The global success of mRNA vaccines has underscored the pivotal role of lipid nanoparticles (LNPs), yet how subtle chemical variations in ionizable lipids and their formulation parameters orchestrate complex immune landscapes remains largely elusive. Here, we report a novel ionizable lipid, N4Z, and demonstrate that its distinct chemical signature selectively intensifies early innate immune programs […]
Droplet-compatible single-cell DNA methylation sequencing with PreTIC
Single-cell DNA methylation sequencing has remained technically specialized due to challenges of interfacing conversion chemistry with droplet microfluidics. We introduce pre-tagmentation in situ conversion (PreTIC), which enables whole-methylome profiling on a commercial droplet platform using off-the-shelf reagents. With PreTIC, we produce over 13,000 single-cell methylomes from fixed frozen cells in two days and resolve cell-specific […]
Zero-Shot Generation of Protein Conformational Ensembles Through AlphaFold Latent Flooding
Despite transformative advances in protein structure prediction, generating conformational ensembles directly from sequence in an efficient and accessible manner remains a central challenge. We introduce a heuristic importance sampling framework for the zero-shot prediction of functionally relevant, conformationally diverse structures, bypassing the need for extensive physics-based modeling or prior domain knowledge. Guided by an analysis […]
Resolving in vitro heterogeneity of host functional responses to HCoV-229E via single-cell analyses
Understanding host-pathogen interactions at the molecular level is essential to elucidating the mechanisms that govern immunity and pathogenesis. While diverse responses to viral infection have been documented, it remains unclear if this variability arises from the complex host milieu or represents an intrinsic property of the infection itself. To investigate this, we performed single-cell (sc) […]
CGAgentX: Agentic AI Framework to Develop Transferable Coarse-Grained Models
We present CGAgentX, a general autonomous multi-agent framework in which specialized LLM-based agents coordinate the optimization of coarse-grained (CG) model parameters to reproduce target properties. Using polar solvents dimethyl sulfoxide (DMSO) and N,N-dimethylacetamide (DMA) as representative case studies, we demonstrate the framework’s capability to develop CG models that accurately reproduce key properties from atomistic simulations […]
Hornbill abundance and habitat correlates in Kali Tiger Reserve, Western Ghats, India-Insights from collaborative monitoring
The future of species, particularly large-bodied birds, under climate threats, is increasingly unclear. Protected areas (PAs) can mitigate the impacts of global change but are not completely immune. This makes it imperative to monitor populations even inside PAs. In the forests of the Western Ghats, three hornbill species are found: Malabar Grey Hornbill, Malabar Pied […]
Simulating Multi-Colour Single-Molecule Localisation Microscopy Using an RGB Camera
High-order multiplexing in single-molecule localisation microscopy (SMLM) is limited by trade-offs between spectral discrimination, imaging speed, and experimental complexity. Here, we show that RGB cameras provide a simple and scalable solution for multi-colour SMLM by exploiting their intrinsic spectral sensitivity for statistical fluorophore discrimination. Using a realistic simulation framework incorporating experimentally derived photon budgets, optical […]
Relative Index of Chimeric Expression (RICE) Analysis: A Quantitative Approach for Chimeric RNAs Using FusionBlaster
Chimeric RNA molecules, which contain nucleotide sequences originating from multiple genes, are generated by chromosomal rearrangements, transcriptional read-throughs, or trans-splicing between separate parental transcripts. Chimeric RNAs have been functionally validated in both pathological and normal healthy physiological contexts indicating the biological significance of chimeric RNA expression. There is, however, currently no standard for computationally quantifying […]