X-SPEAR: An Extensible Framework for Spatial Panel Evaluation and Refinement
Abstract
Targeted spatial transcriptomics platforms such as 10x Genomics Xenium measure a predefined panel of genes. A gene is usually detected in fewer cells in the spatial assay than in the single-cell RNA sequencing (scRNA-seq) reference used to choose it, by an amount that differs from gene to gene. We present eXtensible Spatial Panel Evaluation And Refinement (X- SPEAR), a framework for designing and checking Xenium gene panels. Its marker-selection method, Decision-rule Aggregation for Rare-cell Typing (DART), learns short Boolean gene rules and keeps several gene-disjoint rules per cell type. DART first thins the reference to per-gene detection rates measured in a previous experiment, which we call a Xenium prior, so no Xenium data from the target sample are needed before the panel is ordered. A Xenium prior helped most when it matched the target’s assay chemistry and species, even when it came from a different tissue, and a mismatched prior could lower accuracy. With such a prior, DART outperformed four marker-selection methods on held-out Xenium data from ovarian cancer, mouse brain and cervical cancer at matched panel size: by 0.04–0.10 macro-averaged F 1 score (macro- F 1 ) over the Wilcoxon rank-sum test, 0.04–0.08 over COSine similarity-based marker Gene identification (COSG), 0.10–0.17 over Necessary and Sufficient Forest (NS-Forest) and 0.04–0.08 over the probe-set selection method Spapros. It reached the Wilcoxon test’s best accuracy with 42–69% fewer genes. DART’s rules agree with the classifier that uses the panel and name recognisable marker programs for each cell type. X-SPEAR also checks the probes of any panel for predicted off-target transcripts that are expressed in other cell types. X-SPEAR is available as an open-source Python package.
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BibTeX
@misc{patel2026xspear,
title = {{X-SPEAR: An Extensible Framework for Spatial Panel Evaluation and Refinement}},
author = {Rushil Patel and Bryant Duong and Veer Patel and Rachel Lyn-Sue and Kyungbin Oh and Yuyan Cheng},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.756865},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.756865v1},
note = {CC0},
}
RIS
TY - UNPB
TI - X-SPEAR: An Extensible Framework for Spatial Panel Evaluation and Refinement
AU - Rushil Patel
AU - Bryant Duong
AU - Veer Patel
AU - Rachel Lyn-Sue
AU - Kyungbin Oh
AU - Yuyan Cheng
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.756865
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.756865v1
AB - Targeted spatial transcriptomics platforms such as 10x Genomics Xenium measure a predefined panel of genes. A gene is usually detected in fewer cells in the spatial assay than in the single-cell RNA sequencing (scRNA-seq) reference used to choose it, by an amount that differs from gene to gene. We present eXtensible Spatial Panel Evaluation And Refinement (X- SPEAR), a framework for designing and checking Xenium gene panels. Its marker-selection method, Decision-rule Aggregation for Rare-cell Typing (DART), learns short Boolean gene rules and keeps several gene-disjoint rules per cell type. DART first thins the reference to per-gene detection rates measured in a previous experiment, which we call a Xenium prior, so no Xenium data from the target sample are needed before the panel is ordered. A Xenium prior helped most when it matched the target’s assay chemistry and species, even when it came from a different tissue, and a mismatched prior could lower accuracy. With such a prior, DART outperformed four marker-selection methods on held-out Xenium data from ovarian cancer, mouse brain and cervical cancer at matched panel size: by 0.04–0.10 macro-averaged F 1 score (macro- F 1 ) over the Wilcoxon rank-sum test, 0.04–0.08 over COSine similarity-based marker Gene identification (COSG), 0.10–0.17 over Necessary and Sufficient Forest (NS-Forest) and 0.04–0.08 over the probe-set selection method Spapros. It reached the Wilcoxon test’s best accuracy with 42–69% fewer genes. DART’s rules agree with the classifier that uses the panel and name recognisable marker programs for each cell type. X-SPEAR also checks the probes of any panel for predicted off-target transcripts that are expressed in other cell types. X-SPEAR is available as an open-source Python package.
SN - 2692-8205
ER -