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Updated: Mar 7, 2026

Comprehensive Spatial Profiling of Species-agnostic Transcriptomes via Stereo-seq
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Castl: robust identification of spatially variable genes in spatial transcriptomics via an ensemble-based framework.

Yiyi Yu1, Jiyuan Yang2, Ping-An He1

  • 1Department of Mathematics, College of Science, Zhejiang Sci-Tech University, 928 2nd Avenue, Qiantang District, Hangzhou, Zhejiang 310018, China.

Briefings in Bioinformatics
|March 6, 2026
PubMed
Summary
This summary is machine-generated.

Castl is a new computational framework that integrates multiple methods to identify spatially variable genes (SVGs) in tissues. It accurately detects spatial patterns and controls false discoveries across diverse datasets.

Keywords:
consensus frameworkspatial resolved transcriptomicsspatially variable genes

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Area of Science:

  • Genomics
  • Bioinformatics
  • Computational Biology

Background:

  • Spatially resolved transcriptomics enables the study of tissue organization.
  • Identifying spatially variable genes (SVGs) is crucial for this field.
  • Existing SVG identification methods have limitations, including sensitivity variability and high false discovery rates (FDRs) due to algorithm-specific assumptions.

Purpose of the Study:

  • To develop a robust and flexible framework for identifying spatially variable genes (SVGs).
  • To address the limitations of existing SVG detection methods, such as assumption-dependency and inconsistent performance.
  • To provide a standardized approach for feature discovery in complex biological systems using spatial transcriptomics data.

Main Methods:

  • Developed Castl, an ensemble-based computational framework for SVG identification.
  • Integrated multiple SVG detection methods using statistically designed aggregation modules.
  • Evaluated Castl's performance on both simulated and real-world spatial transcriptomics datasets.

Main Results:

  • Castl consistently identifies biologically meaningful spatial gene expression patterns.
  • The framework effectively mitigates biases inherent in individual detection methods.
  • Castl demonstrates robust control of false discovery rates (FDRs) across diverse biological contexts, resolutions, and spatial technologies.
  • Comprehensive evaluations confirmed Castl's superior performance compared to existing methods.

Conclusions:

  • Castl offers a flexible, assumption-free framework for reliable SVG identification.
  • This ensemble approach provides a standardized foundation for spatially informed feature discovery.
  • Castl enhances the analysis of complex biological systems through accurate spatial transcriptomics data interpretation.