{"doi":"10.1093/bioinformatics/btab498","title":"D-MANOVA: fast distance-based multivariate analysis of variance for large-scale microbiome association studies","abstract":"SUMMARY: PERMANOVA (permutational multivariate analysis of variance based on distances) has been widely used for testing the association between the microbiome and a covariate of interest. Statistical significance is established by permutation, which is computationally intensive for large sample sizes. As large-scale microbiome studies, such as American Gut Project (AGP), become increasingly popular, a computationally efficient version of PERMANOVA is much needed. To achieve this end, we derive the asymptotic distribution of the PERMANOVA pseudo-F statistic and provide analytical P-value calculation based on chi-square approximation. We show that the asymptotic P-value is close to the PERMANOVA P-value even under a moderate sample size. Moreover, it is more accurate and an order-of-magnitude faster than the permutation-free method MDMR. We demonstrated the use of our procedure D-MANOVA on the AGP dataset. AVAILABILITY AND IMPLEMENTATION: D-MANOVA is implemented by the dmanova function in the CRAN package GUniFrac. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.","journal":"Bioinformatics","year":2021,"id":170179,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":388898,"name":"Xianyang Zhang","orcid":"0000-0002-2512-1816","position":1,"is_corresponding":false},{"id":252214,"name":"Jun Chen","orcid":"0000-0002-1273-5624","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-18T23:46:19.728805Z","pmid":"34255026","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":[]}