{"doi":"10.1101/2020.10.01.322362","title":"Testcrosses are an efficient strategy for identifying <i>cis</i> regulatory variation: Bayesian analysis of allele specific expression (BASE)","abstract":"ABSTRACT Allelic imbalance (AI) occurs when alleles in a diploid individual are differentially expressed and indicates cis acting regulatory variation. What is the distribution of allelic effects in a natural population? Are all alleles the same? Are all alleles distinct? Tests of allelic effect are performed by crossing individuals and comparing expression between alleles directly in the F1. However, a crossing scheme that compares alleles pairwise is a prohibitive cost for more than a handful of alleles as the number of crosses is at least ( n 2 -n)/2 where n is the number of alleles. We show here that a testcross design followed by a hypothesis test of AI between testcrosses can be used to infer differences between non-tester alleles, allowing n alleles to be compared with n crosses. Using a mouse dataset where both testcrosses and direct comparisons have been performed, we show that ∼75% of the predicted differences between non-tester alleles are validated in a background of ∼10% differences in AI. The testing for AI involves several complex bioinformatics steps. BASE is a complete bioinformatics pipeline that incorporates state-of-the-art error reduction techniques and a flexible Bayesian approach to estimating AI and formally comparing levels of AI between conditions. The modular structure of BASE has been packaged in Galaxy, made available in Nextflow and sbatch. ( https://github.com/McIntyre-Lab/BASE_2020 ). In the mouse data, the direct test identifies more cis effects than the testcross. Cis-by-trans interactions with trans -acting factors on the X contributing to observed cis effects in autosomal genes in the direct cross remains a possible explanation for the discrepancy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131177,"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":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331151,"name":"Alison M. Morse","orcid":"0000-0003-4286-6489","position":1,"is_corresponding":false},{"id":584567,"name":"J. E. Borgert","orcid":"0009-0002-8083-8358","position":2,"is_corresponding":false},{"id":584568,"name":"Zihao Liu","orcid":"0000-0002-0524-3621","position":3,"is_corresponding":false},{"id":585130,"name":"Kelsey Sinclair","orcid":null,"position":4,"is_corresponding":false},{"id":585131,"name":"Gavin Gamble","orcid":null,"position":5,"is_corresponding":false},{"id":323089,"name":"Fei Zou","orcid":"0000-0002-6637-3593","position":6,"is_corresponding":false},{"id":307664,"name":"Jeremy R. B. Newman","orcid":"0000-0001-8486-2801","position":7,"is_corresponding":false},{"id":584569,"name":"Luis León‐Novelo","orcid":"0000-0002-2595-3583","position":8,"is_corresponding":false},{"id":584570,"name":"Fabio Marroni","orcid":"0000-0002-1556-5907","position":9,"is_corresponding":false},{"id":307666,"name":"Lauren M. McIntyre","orcid":"0000-0002-0077-3359","position":10,"is_corresponding":false},{"id":584566,"name":"Brecca Miller","orcid":"0000-0002-0560-5397","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:16:00.235845Z","pmid":null,"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":[]}