bioRxiv Science⌕ Search

bioRxiv · 10.64898/2025.12.09.693192

BatchSVG: identifying batch-biased genes in the application of spatially variable gene detection

Abstract

1A standard task in the analysis of spatially resolved transcriptomics data is to identify spatially variable genes (SVGs). This is most commonly done within one tissue section at a time because the spatial relationships between the tissue sections are typically unknown. However, large-scale spatial atlases are being generated, for example across hundreds of donors, where the goal is to identify a common set of SVGs to use for downstream analyses. One challenge is how to identify and remove SVGs that are associated with a known bias or technical artifact, such as the slide or capture area, which can lead to poor performance in downstream analyses, such as spatial domain detection. Here, we introduce BatchSVG, a tool to identify batch-biased genes in the application of SVG detection. Our approach compares the rank of per-gene deviance under a binomial model (i) with and (ii) without including a covariate in the model that is associated with the known bias or technical artifact. If the rank of a gene changes significantly between these, then we infer that this gene is likely associated with the bias or technical artifact and should be removed from the downstream analysis. We consider two SRT datasets and show how our model can improve the results of downstream analysis.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Shah, K. H., Hou, C., Thompson, J. R., Hicks, S. C.. 2025-12-12. BatchSVG: identifying batch-biased genes in the application of spatially variable gene detection. https://doi.org/10.64898/2025.12.09.693192

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Longitudinal miRNA-mRNA Profiling Reveals Network Reorganization in Preeclampsia

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity. Temporal dynamics of molecular dysregulation across pregnancy remain poorly understood. We performed longitudinal RNA sequencing of maternal whole blood to characterize miRNA-mRNA regulatory network evolution in PE. Methods: Whole-blood samples from early (M1: 10-18 weeks) and late pregnancy (M2: 32-38 weeks) were analyzed from 43 PE cases and 106 normotensive controls, including 109 paired samples (36 PE cases, 73 controls). Differential expression, temporal classification, pathway enrichment, and miRNA-mRNA network integration were performed. Placental expression support was assessed using internal RNA-seq and public databases. Key miRNA-mRNA interactions were experimentally validated in HTR-8/SVneo trophoblast cells. Results: PE exhibited marked temporal reorganization of miRNA-mRNA networks, with strongly opposing temporal effect sizes across overlapping miRNA and mRNA features (Spearman {rho} = -0.82, P < 0.0001). PI3K/AKT/mTORC1 signaling showed biphasic reversal (NES = +1.46, FDR = 0.028 at M1; NES = -1.64, FDR = 0.025 at M2), and heme-metabolism programs showed progressive suppression (2.1-fold NES intensification; FDR < 0.05 at both timepoints). Network analysis identified 29 high-confidence biphasic miRNA-mRNA pairs, including convergent targeting of ADGRA2 by three miRNAs and HSD17B1 by three miRNAs. miR-101-3p overexpression reduced DEPP1 mRNA (~40%) and protein (~26%) in trophoblast cells (P < 0.01), supporting a FOXO-DEPP1 axis. Blood-derived pairs showed pathway convergence with placental VGLL3-centered programs (PI3K/AKT, FOXO, TGF-{beta}, trophoblast differentiation). Conclusions: PE is associated with predominantly stage-specific or biphasic miRNA-mRNA network reorganization, with PI3K/AKT/mTORC1 dynamic remodeling and progressive heme-metabolism suppression. These findings support gestational-age-specific biomarker development and identify regulatory axes, including miR-101-3p [->] DEPP1, for mechanistic investigation.

genomics↗

MicroDUET: a dual-headed genomic foundation model for pathogen surveillance

Pathogen genomic surveillance works from raw reads, assembled genomes and alignments, representations that are slow and costly to compare at scale. Compact embeddings from genomic language models offer an alternative, but surveillance requires resolving both evolutionary ancestry (phylogeny) and phenotypic capability (function) - which need not co-vary. Here we present MicroDUET, which adapts a 26.6-million-parameter ProkBERT backbone with two 3.5-million-parameter adapter heads: a phylogeny head trained contrastively on genome windows from the same microbes, and a function head trained to identify genes across taxa. On held-out retrieval benchmarks, the phylogeny head returned the correct species for 80.3% and 66.6% of cellular and viral queries, and the function head the correct gene family for 97.3% and 97.2%, reaching 74.4% accuracy on an independent antimicrobial resistance-class benchmark. Across all three benchmarks MicroDUET outranked 17 other genomic encoders. Without training on lineage, clade or drug-susceptibility tasks, MicroDUET identified Mycobacterium tuberculosis and mpox virus lineages and clades (0.965, 0.975 accuracy), discriminated rifampicin resistance without lineage adjustment (AUROC 0.985), and retrospectively identified an emerging mpox lineage as anomalous (AUROC 0.974). MicroDUET operates 10^3 - 10^4 times faster than single-threaded sequence-based alignments. MicroDUET therefore provides a compact, reusable representation for scalable pathogen surveillance and sequence triage.

genomics↗

A chromosome-level genome assembly of northern dragonhead, Dracocephalum ruyschiana L., 1753

We present a chromosome-level genome assembly for the vascular plant northern dragonhead, Dracocephalum ruyschiana. The assembly comprises two pseudo-haplotypes, hap1 and hap2, of 661 Mb and 681 Mb, with 93.6% and 92.5%, respectively, scaffolded into seven chromosomes each - in line with the known karyotype. Assembly quality was high, with conserved single-copy ortholog completeness scores of 97.9% and 97.8%, combined k-mer completeness of 98.1%, and 38,141 and 38,617 annotated protein-coding genes for hap1 and hap2, respectively. This assembly provides a high-quality genomic resource for future research and conservation of northern dragonhead, as well as the endangered northern dragonhead sap beetle, which depends on the plant for reproduction and whose genome assembly is described in a complementary genome note.

genomics↗