{"doi":"10.1371/journal.pcbi.1008789","title":"Detection of gene cis-regulatory element perturbations in single-cell transcriptomes","abstract":"We introduce poly-adenine CRISPR gRNA-based single-cell RNA-sequencing (pAC-Seq), a method that enables the direct observation of guide RNAs (gRNAs) in scRNA-seq. We use pAC-Seq to assess the phenotypic consequences of CRISPR/Cas9 based alterations of gene cis-regulatory regions. We show that pAC-Seq is able to detect cis-regulatory-induced alteration of target gene expression even when biallelic loss of target gene expression occurs in only ~5% of cells. This low rate of biallelic loss significantly increases the number of cells required to detect the consequences of changes to the regulatory genome, but can be ameliorated by transcript-targeted sequencing. Based on our experimental results we model the power to detect regulatory genome induced transcriptomic effects based on the rate of mono/biallelic loss, baseline gene expression, and the number of cells per target gRNA.","journal":"PLoS Computational Biology","year":2021,"id":205494,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9562,"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":788799,"name":"Oscar Juez","orcid":"0000-0002-2748-2009","position":1,"is_corresponding":false},{"id":730405,"name":"Qing Chen","orcid":"0000-0002-8450-9300","position":2,"is_corresponding":false},{"id":42916,"name":"Budhaditya Banerjee","orcid":null,"position":3,"is_corresponding":false},{"id":540647,"name":"Lendy Chu","orcid":null,"position":4,"is_corresponding":false},{"id":235721,"name":"Max W. Shen","orcid":"0000-0002-4226-1861","position":5,"is_corresponding":false},{"id":788800,"name":"May Sabry","orcid":"0000-0003-2466-4066","position":6,"is_corresponding":false},{"id":789252,"name":"Ive Logister","orcid":null,"position":7,"is_corresponding":false},{"id":43159,"name":"Richard I. Sherwood","orcid":"0000-0001-7427-7713","position":8,"is_corresponding":false},{"id":408579,"name":"David K. Gifford","orcid":"0000-0003-1709-4034","position":9,"is_corresponding":false},{"id":499623,"name":"Grace Hui Ting Yeo","orcid":"0000-0002-8920-8208","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:33.996102Z","pmid":"33711017","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":[]}