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PreprintCC BY-NC-NDbioRxiv

BiNVaST: niche boundary-preserving and synthetic data-guided variational autoencoders for concordant inference across high-resolution spatial transcriptomic platforms

  1. 1St. Jude Children's Research Hospital

Abstract

High-resolution spatial transcriptomics (ST) enables subcellular spatially resolved transcript profiling but remains difficult to annotate in complex tissues because of gene coverage and super sparseness in expression. These challenges are amplified in cancer research, where neoplastic cell states and rare immune cells in tumor microenvironment are often poorly captured by generic references and/or cell typing tools exclusively built on molecular profile. Here, we present BiNVaST, a niche boundary-preserving and dual-branch variational autoencoder fused with statistical simulator for reliable cell typing across multiple spatial platforms. It generates platform-adjusted in silico training data by integrating query spatial profile and user-defined pre-annotated single-cell reference through Singular Value Decomposition and Optimal Transport, combining molecular similarity and spatial proximity to predict segmented cell labels. BiNVaST was benchmarked against existing methods across Xenium, CosMx, Stereo-seq, Visium HD platforms using six specimens from four tissue types. This tool is sensitive in detecting divergent tumor cell states and improves the cross-platform concordance, distinguishing disease-specific neoplastic and non-neoplastic cellular subpopulations and supporting robust cellular or niche inferences in heterogeneous tissues.

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BibTeX
@misc{zhang2026binvast,
  title = {{BiNVaST: niche boundary-preserving and synthetic data-guided variational autoencoders for concordant inference across high-resolution spatial transcriptomic platforms}},
  author = {J. Zhang and L. Li and L. Liu and B. L. Fridley and C. Cheng and J. T. Plummer and G. Wu and J. C.-H. Chiang and Q. Li},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.15.759369},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.15.759369v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - BiNVaST: niche boundary-preserving and synthetic data-guided variational autoencoders for concordant inference across high-resolution spatial transcriptomic platforms
AU  - J. Zhang
AU  - L. Li
AU  - L. Liu
AU  - B. L. Fridley
AU  - C. Cheng
AU  - J. T. Plummer
AU  - G. Wu
AU  - J. C.-H. Chiang
AU  - Q. Li
PY  - 2026
DA  - 2026/10/15
PB  - bioRxiv
DO  - 10.64898/2026.10.15.759369
UR  - https://www.biorxiv.org/content/10.64898/2026.10.15.759369v1
AB  - High-resolution spatial transcriptomics (ST) enables subcellular spatially resolved transcript profiling but remains difficult to annotate in complex tissues because of gene coverage and super sparseness in expression. These challenges are amplified in cancer research, where neoplastic cell states and rare immune cells in tumor microenvironment are often poorly captured by generic references and/or cell typing tools exclusively built on molecular profile. Here, we present BiNVaST, a niche boundary-preserving and dual-branch variational autoencoder fused with statistical simulator for reliable cell typing across multiple spatial platforms. It generates platform-adjusted in silico training data by integrating query spatial profile and user-defined pre-annotated single-cell reference through Singular Value Decomposition and Optimal Transport, combining molecular similarity and spatial proximity to predict segmented cell labels. BiNVaST was benchmarked against existing methods across Xenium, CosMx, Stereo-seq, Visium HD platforms using six specimens from four tissue types. This tool is sensitive in detecting divergent tumor cell states and improves the cross-platform concordance, distinguishing disease-specific neoplastic and non-neoplastic cellular subpopulations and supporting robust cellular or niche inferences in heterogeneous tissues.
ER  -