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Drake, O. R.

Publications and source records attributed to Drake, O. R..

4 recordsLinked to original sources

nf_xpatial: A Reproducible Framework for Standardized Preprocessing and Clustering of Xenium Data

Recent advances in spatial transcriptomics have enabled the profiling of increasingly larger numbers of genes while retaining single-cell and subcellular resolution in situ. However, standardized bioinformatics workflows for analyzing these datasets have lagged behind, with existing pipelines focusing primarily on image processing and cell segmentation. To address this gap, we present nf_xpatial, a best-practices Nextflow pipeline for the downstream analysis of 10x Genomics Xenium data. The pipeline performs quality control, filtering, log and cell area normalization, multi-sample integration, and both expression-driven and spatially informed clustering across systematic parameter sweeps, allowing users to evaluate and compare clustering resolutions and spatial modeling parameters within a single reproducible run. Overall, nf_xpatial streamlines the processing of Xenium data from platform outputs to integrated single-cell and spatial clustering datasets, providing a standardized starting point from which biologists can fine-tune parameters and proceed to hypothesis-driven spatial analyses.

bioinformatics↗

A conserved population of genetically defined striatal neurons gates opioid reward

A longstanding paradox in striatal circuit architecture is that opioid reward depends on -opioid receptors ({micro}ORs) in nucleus accumbens medium spiny neurons (MSNs), yet {micro}OR function is not explained by the canonical D1/direct and D2/indirect pathway organization. Here, we identify a rare MSN population marked by Chst9 that exhibits exceptionally high expression of the {micro}OR and is conserved across species. Notably, Chst9-MSNs comprise a specialized indirect pathway striatal neuron subtype that is molecularly and spatially distinct from canonical striatal populations. Opioids robustly silence Chst9-MSNs, and selective deletion of Oprm1 from this population abolishes fentanyl-conditioned place preference. These findings establish Chst9-MSNs as a critical substrate for opioid reward and define a new cellular framework for therapies targeting opioid use disorder.

neuroscience↗

Persistent vulnerability to heroin relapse across the adult lifespan in rats

Relapse to opioid use during abstinence is often triggered by drug-associated cues but the persistence of this effect across the lifespan is unknown. Using a rat model, we found that relapse provoked by heroin-predictive discriminative stimuli persisted for over one year of abstinence, suggesting enduring, potentially lifelong opioid relapse vulnerability.

animal behavior and cognition↗

MultipleXed Population Selection and Enrichment single nucleus RNA sequencing (XPoSE-seq) enables sample identity retention during transcriptional profiling of rare populations

Single nucleus RNA-sequencing is critical in deciphering tissue heterogeneity and identifying rare populations. However, current high throughput techniques are not optimized for rare target populations and require tradeoffs in design due to feasibility. We provide a novel snRNA pipeline, MulipleXed Population Selection and Enrichment snRNA-sequencing (XPoSE-seq), to enable targeted snRNA-seq experiments and in-depth transcriptomic characterization of rare target populations while retaining individual sample identity.

neuroscience↗