{"doi":"10.1145/3746252.3761240","title":"MUSE: A Multi-slice Joint Analysis Method for Spatial Transcriptomics Experiments","abstract":"Recent advances in spatial transcriptomics (ST) and cost reductions have enabled large-scale multi-slice ST data generation, enhancing the statistical power to detect subtle biological signals. However, cross-slice inconsistencies and data quality variability present significant analytical challenges. To overcome these limitations, we developed MUSE, a computational framework designed for multislice joint embedding, spatial domain identification, and gene expression imputation. Specifically, MUSE integrates a two-module architecture to ensure robust cross-slice alignment and data harmonization. The alignment module models each slice as a graph and employs optimal transport to align cells across slices while preserving spatial continuity. The optimization module further refines integration by incorporating an alignment loss, allowing lower-quality data to leverage structural information from higher-quality slices. Additionally, MUSE generates virtual neighbors from aligned cells, enriching contextual information and mitigating data sparsity. These design principles enable seamless integration with existing single-slice methods, extending their applicability to multi-slice ST analysis. To comprehensively evaluate its performance, we applied MUSE to 12 real and 48 simulated datasets spanning a range of data qualities. Across all metrics, MUSE consistently outperformed existing methods in cross-slice consistency, spatial domain identification, and gene expression imputation. To promote accessibility and adoption, we provide MUSE as an open-source software package. As multi-slice ST datasets become increasingly prevalent, MUSE provides a robust and extensible framework designed to effectively integrate growing numbers of slices, thereby advancing the analysis of tissue architectures and spatial gene expression in complex biological systems.","journal":"PubMed","year":2025,"id":559466,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1460701,"name":"Xi Li","orcid":"0009-0008-9006-4943","position":1,"is_corresponding":false},{"id":1460702,"name":"Zhiqing Xiao","orcid":"0009-0007-4889-644X","position":2,"is_corresponding":false},{"id":63595,"name":"Rex Ying","orcid":"0000-0002-5856-5229","position":3,"is_corresponding":false},{"id":13180,"name":"Jing Zhang","orcid":"0000-0002-5970-0509","position":4,"is_corresponding":false},{"id":21388,"name":"Ziheng Duan","orcid":"0000-0003-4696-0042","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41527556","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}