{"doi":"10.1002/sim.70213","title":"scCOSMIX: A Mixed‐Effects Framework for Differential Coexpression and Transcriptional Interactions Modeling in Single‐Cell RNA‐Seq","abstract":"Advancements in single-cell RNA-sequencing (scRNA-seq) technologies generate a wealth of gene expression data that provide exciting opportunities for studying gene-gene interactions systematically at individual cell resolution. Genetic interactions within a cell are tightly regulated and often highly dynamic in response to internal cellular signals and external stimuli. Evidence of these dynamic interactions can often be observed in scRNA-seq data by examining conditional co-expression changes. Existing approaches for studying these dynamic interaction changes in scRNA-seq data do not address the multi-subject hierarchical design commonly considered in single-cell experiments. In this paper, we propose a Mixed-effects framework for differential Coexpression and transcriptional interaction modeling in Single-Cell RNA-seq (scCOSMiX) to account for the cell-cell correlation from the same individual. The proposed copula-based approach allows the zero-inflation, marginal, and association parameters to be modeled as functions of covariates with subject-level random effects, to enable analyses to be tailored to the data under consideration. A series of simulation analyses were conducted to evaluate and compare the performance of scCOSMiX to other existing approaches. We applied the proposed method to both droplet and plate-based scRNA-seq data sets GSE266919 and GSE108989 to illustrate its applicability across distinct scRNA-seq experimental protocols.","journal":"Statistics in Medicine","year":2025,"id":571976,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9267,"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":1430632,"name":"Giampiero Marra","orcid":"0000-0002-9010-2646","position":1,"is_corresponding":false},{"id":396954,"name":"Daping Fan","orcid":"0000-0002-4729-761X","position":2,"is_corresponding":false},{"id":52271,"name":"Russell T. Shinohara","orcid":"0000-0001-8627-8203","position":3,"is_corresponding":false},{"id":851553,"name":"Danni Tu","orcid":"0000-0001-8153-1652","position":4,"is_corresponding":false},{"id":292933,"name":"Yen‐Yi Ho","orcid":"0000-0002-3224-3184","position":5,"is_corresponding":false},{"id":1430631,"name":"Anderson Bussing","orcid":"0000-0002-0910-1129","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:57:19.669553Z","pmid":"40772737","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":[]}