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Biology subjects

Chow, P. K.-H.

Publications and source records attributed to Chow, P. K.-H..

3 recordsLinked to original sources

RankMap: Rank-based reference mapping for fast and robust cell type annotation in spatial and single-cell transcriptomics

Accurate cell type annotation is essential for the analysis of single-cell and spatial transcriptomics data. While reference-based annotation methods have been widely adopted, many existing approaches rely on full-transcriptome profiles and incur substantial computational cost, limiting their applicability to large-scale spatial datasets and platforms with partial gene panels. Here, we present RankMap (https://github.com/jinming-cheng/RankMap), an efficient and flexible R package for reference-based cell type annotation across both single-cell and spatial transcriptomics. RankMap transforms gene expression profiles into rank-based representations using the top expressed genes per cell, improving robustness to platform-specific biases and expression scale differences. A multinomial regression model trained with elastic net regularization is then used to predict cell types and associated confidence scores. We benchmarked RankMap on five spatial transcriptomics datasets, including Xenium, MERFISH, and Stereo-seq, as well as two single-cell datasets, and compared it with established methods such as SingleR, Azimuth, and RCTD. RankMap achieved competitive or superior annotation accuracy while consistently reducing runtime compared to existing methods, particularly for large spatial datasets. These results demonstrate that RankMap provides a scalable and robust solution for reference-based cell type annotation in modern single-cell and spatial transcriptomics studies.

bioinformatics↗

Single-cell and spatial atlas of steatotic liver-related hepatocellular carcinoma

Steatotic liver disease-related hepatocellular carcinoma (SLD-HCC) poses significant challenges in liver cancer management. Our current study investigates the tumor microenvironment (TME) of SLD-HCC using single-cell transcriptomic, proteomic and spatial transcriptomic analyses. We identified altered immune-related and lipid metabolism pathways, particularly in regulatory T cells (Tregs) and cancer-associated fibroblasts (CAFs) within the SLD-HCC microenvironment, suggesting distinct cellular adaptations to a high-fat TME and general immunosuppression. Cytometry by time-of-flight revealed a cold and immunosuppressive TME depleted with CD8+ T cells and enriched with Tregs, while spatial transcriptomics uncovered a unique spatial architecture with Treg/CAF clusters specifically located at the tumor margins in SLD-HCC. Crucially, we identified Treg-CAF interactions as a key mediator associated with lack of response to immunotherapy in SLD-HCC. Our findings highlight the intricate immune dynamics of SLD-HCC, indicating potential therapeutic targets to counteract immune evasion and restore anti-tumor immunity in SLD-HCC. HighlightsO_LIThe TME of SLD-HCC exhibits altered immune and lipid pathways C_LIO_LIImmunosuppressive SLD-HCC TME is depleted with CD8+ T cells and enriched with Tregs C_LIO_LISLD-HCC has a unique spatial architecture with Treg-CAF clusters at tumor margins C_LIO_LITreg-CAF interaction via TNFSF14-TNFRSF14 axis mediates immunotherapy resistance C_LI

immunology↗

High-dose drug heat map based on organoid array chip for drug selection with high safety and efficacy

An organoid array chip was developed by adopting a micropillar and microwell structure to test safety and efficacy of drugs using high dose drug heat map. In the chip, we encapsulated patient-derived cells in alginate and grow them to maturity for more than 7 days to form cancer organoids. When screening drug compounds in a high-density organoid array due to lack of number of patient-derived cells, changing media without damage of organoids is a very tedious and difficult process. Organoids grown in conventional well plates needed too many cells and were also easily damaged due to multiple pipetting during maintenance culture or during experimental procedures. To solve those problem, we applied a micropillar and microwell structure to the organoid array. We used patient-derived cells from patients with Glioblastoma multiforme (GBM), the most common and lethal form of central nervous system cancer, to validate the array chip performance. After forming more than 100{micro}m-diameter organoids in 12 x 36 pillar array chip (25mm x 75mm), we tested 70 drug compounds (6 replicates) with high high-dose to find out high safety and efficacy drug candidates. Comparing the drug response of organoids derived from normal cells and cancer cells, we identified four compounds (Dacomitinib, Cediranib, Ly2835219, BGJ398) as drug candidates without toxicity to GBM cells.

cancer biology↗