{"doi":"10.1093/bioinformatics/bts714","title":"Data exploration, quality control and testing in single-cell qPCR-based gene expression experiments","abstract":"<h4>Motivation</h4>Cell populations are never truly homogeneous; individual cells exist in biochemical states that define functional differences between them. New technology based on microfluidic arrays combined with multiplexed quantitative polymerase chain reactions now enables high-throughput single-cell gene expression measurement, allowing assessment of cellular heterogeneity. However, few analytic tools have been developed specifically for the statistical and analytical challenges of single-cell quantitative polymerase chain reactions data.<h4>Results</h4>We present a statistical framework for the exploration, quality control and analysis of single-cell gene expression data from microfluidic arrays. We assess accuracy and within-sample heterogeneity of single-cell expression and develop quality control criteria to filter unreliable cell measurements. We propose a statistical model accounting for the fact that genes at the single-cell level can be on (and a continuous expression measure is recorded) or dichotomously off (and the recorded expression is zero). Based on this model, we derive a combined likelihood ratio test for differential expression that incorporates both the discrete and continuous components. Using an experiment that examines treatment-specific changes in expression, we show that this combined test is more powerful than either the continuous or dichotomous component in isolation, or a t-test on the zero-inflated data. Although developed for measurements from a specific platform (Fluidigm), these tools are generalizable to other multi-parametric measures over large numbers of events.<h4>Availability</h4>All results presented here were obtained using the SingleCellAssay R package available on GitHub (http://github.com/RGLab/SingleCellAssay).","journal":"Bioinformatics","year":2012,"id":1547,"datarank":0.9136964823116548,"base_score":6.091309882077698,"endowment":6.091309882077698,"self_citation_contribution":0.9136964823116548,"citation_network_contribution":0.0,"self_endowment_contribution":0.9136964823116548,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":441,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0536,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2012-12-24","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":18045,"name":"Greg Finak","orcid":"0000-0003-4341-9090","position":1,"is_corresponding":false},{"id":18046,"name":"Pratip K. Chattopadyay","orcid":null,"position":2,"is_corresponding":false},{"id":18047,"name":"Maria Dominguez","orcid":null,"position":3,"is_corresponding":false},{"id":18048,"name":"Laurie Lamoreaux","orcid":null,"position":4,"is_corresponding":false},{"id":18049,"name":"Steven S. Ma","orcid":null,"position":5,"is_corresponding":false},{"id":18050,"name":"Mario Roederer","orcid":"0000-0001-7448-7040","position":6,"is_corresponding":false},{"id":18051,"name":"Raphael Gottardo","orcid":null,"position":7,"is_corresponding":false},{"id":18052,"name":"María Domínguez","orcid":"0000-0002-3329-7862","position":8,"is_corresponding":false},{"id":18053,"name":"Schmidt Steven","orcid":null,"position":9,"is_corresponding":false},{"id":18054,"name":"Raphaël Gottardo","orcid":"0000-0002-3867-0232","position":10,"is_corresponding":false},{"id":18044,"name":"Andrew McDavid","orcid":"0000-0002-6581-1213","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","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":[]}