An Exploratory Multiome Analysis of a BCG-Associated HSPC Signature: Trained-Immunity Marker in Blood and an Adverse Prognostic Association in Tumour
Abstract
Intravesical Bacillus Calmette--Guérin (BCG) is an established treatment for non-muscle-invasive bladder cancer (NMIBC), and recent evidence indicates that bladder BCG induces transcriptional and chromatin changes in hematopoietic stem and progenitor cells (HSPCs). However, the joint multi-omic structure of these BCG-associated changes and its potential to define transferable molecular signatures remain less well characterized. This study performed an exploratory integrative analysis of paired single-cell RNA-seq and ATAC-seq data from two NMIBC patients sampled before and after BCG treatment. Following preprocessing and barcode-level integration, 653 HSPCs were analysed using Multi-Omics Factor Analysis (MOFA+) with 2,000 HSPC-specific variable genes and 25,000 variable chromatin-accessibility peaks. Of ten latent factors, Factor~1 showed the strongest association with BCG status (r=0.495) and captured variation across both molecular views. RNA weights from Factor~1 were used to derive candidate gene signatures that showed partial consistency across patient-specific models. Cross-context evaluation showed associations with overall survival in TCGA-BLCA and recurrence in GSE199471, while a subset of signature genes showed consistent directional changes in monocytes following BCG vaccination in GSE184241. Together, these findings identify a candidate multi-omic axis associated with BCG exposure and suggest that its derived molecular signatures exhibit context-dependent behaviour across distinct biological and clinical settings.
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BibTeX
@misc{ruhama2026exploratory,
title = {{An Exploratory Multiome Analysis of a BCG-Associated HSPC Signature: Trained-Immunity Marker in Blood and an Adverse Prognostic Association in Tumour}},
author = {Sadia Ruhama},
howpublished = {arXiv},
year = {2026},
month = oct,
doi = {10.48550/arxiv.2610.32999},
eprint = {2610.32999},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2610.32999},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - An Exploratory Multiome Analysis of a BCG-Associated HSPC Signature: Trained-Immunity Marker in Blood and an Adverse Prognostic Association in Tumour
AU - Sadia Ruhama
PY - 2026
DA - 2026/10/06
PB - arXiv
DO - 10.48550/arxiv.2610.32999
UR - https://arxiv.org/abs/2610.32999
AB - Intravesical Bacillus Calmette--Guérin (BCG) is an established treatment for non-muscle-invasive bladder cancer (NMIBC), and recent evidence indicates that bladder BCG induces transcriptional and chromatin changes in hematopoietic stem and progenitor cells (HSPCs). However, the joint multi-omic structure of these BCG-associated changes and its potential to define transferable molecular signatures remain less well characterized. This study performed an exploratory integrative analysis of paired single-cell RNA-seq and ATAC-seq data from two NMIBC patients sampled before and after BCG treatment. Following preprocessing and barcode-level integration, 653 HSPCs were analysed using Multi-Omics Factor Analysis (MOFA+) with 2,000 HSPC-specific variable genes and 25,000 variable chromatin-accessibility peaks. Of ten latent factors, Factor~1 showed the strongest association with BCG status (r=0.495) and captured variation across both molecular views. RNA weights from Factor~1 were used to derive candidate gene signatures that showed partial consistency across patient-specific models. Cross-context evaluation showed associations with overall survival in TCGA-BLCA and recurrence in GSE199471, while a subset of signature genes showed consistent directional changes in monocytes following BCG vaccination in GSE184241. Together, these findings identify a candidate multi-omic axis associated with BCG exposure and suggest that its derived molecular signatures exhibit context-dependent behaviour across distinct biological and clinical settings.
ER -