{"doi":"10.1093/bib/bbac084","title":"TWO-SIGMA-G: a new competitive gene set testing framework for scRNA-seq data accounting for inter-gene and cell–cell correlation","abstract":"We propose TWO-SIGMA-G, a competitive gene set test for scRNA-seq data. TWO-SIGMA-G uses a mixed-effects regression model based on our previously published TWO-SIGMA to test for differential expression at the gene-level. This regression-based model provides flexibility and rigor at the gene-level in (1) handling complex experimental designs, (2) accounting for the correlation between biological replicates and (3) accommodating the distribution of scRNA-seq data to improve statistical inference. Moreover, TWO-SIGMA-G uses a novel approach to adjust for inter-gene-correlation (IGC) at the set-level to control the set-level false positive rate. Simulations demonstrate that TWO-SIGMA-G preserves type-I error and increases power in the presence of IGC compared with other methods. Application to two datasets identified HIV-associated interferon pathways in xenograft mice and pathways associated with Alzheimer's disease progression in humans.","journal":"Briefings in Bioinformatics","year":2022,"id":284626,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254661,"name":"Ming Hu","orcid":"0000-0003-0987-2916","position":1,"is_corresponding":false},{"id":537938,"name":"Liang Cheng","orcid":"0000-0001-6049-5293","position":2,"is_corresponding":false},{"id":11808,"name":"John A. Wrobel","orcid":"0000-0002-5828-9359","position":3,"is_corresponding":false},{"id":439350,"name":"Kirk C. Wilhelmsen","orcid":"0000-0002-4432-8302","position":4,"is_corresponding":false},{"id":255662,"name":"Lishan Su","orcid":"0000-0002-0350-5560","position":5,"is_corresponding":false},{"id":962386,"name":"Yun Li","orcid":"0000-0002-5982-9265","position":6,"is_corresponding":false},{"id":37265,"name":"Di Wu","orcid":"0000-0001-8331-2357","position":7,"is_corresponding":false},{"id":962385,"name":"Eric Van Buren","orcid":"0000-0003-4256-8705","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T00:29:36.828109Z","pmid":"35325048","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":[]}