{"doi":"10.1101/2021.07.17.452050","title":"Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler","abstract":"Summary A primary obstacle in translating genetics and genomics data into therapeutic strategies is elucidating the cellular programs affected by genetic variants and genes associated with human diseases. Broadly applicable high-throughput, unbiased assays offer a path to rapidly characterize gene and variant function and thus illuminate disease mechanisms. Here, we report LipocyteProfiler, an unbiased high-throughput, high-content microscopy assay that is amenable to large-scale morphological and cellular profiling of lipid-accumulating cell types. We apply LipocyteProfiler to adipocytes and hepatocytes and demonstrate its ability to survey diverse cellular mechanisms by generating rich context-, and process-specific morphological and cellular profiles. We then use LipocyteProfiler to identify known and novel cellular programs altered by polygenic risk of metabolic disease, including insulin resistance, waist-to-hip ratio and the polygenic contribution to lipodystrophy. LipocyteProfiler paves the way for large-scale forward and reverse phenotypic profiling in lipid-storing cells, and provides a framework for the unbiased identification of causal relationships between genetic variants and cellular programs relevant to human disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":213787,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9459,"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":51605,"name":"Sophie Strobel","orcid":"0000-0002-4667-4874","position":1,"is_corresponding":false},{"id":253982,"name":"Josep M. Mercader","orcid":"0000-0001-8494-3660","position":2,"is_corresponding":false},{"id":31456,"name":"Hesam Dashti","orcid":"0000-0003-4566-0582","position":3,"is_corresponding":false},{"id":806373,"name":"Alina Ainbinder","orcid":"0000-0001-8851-5620","position":4,"is_corresponding":false},{"id":136206,"name":"Julius Honecker","orcid":"0000-0002-1592-7023","position":5,"is_corresponding":false},{"id":804438,"name":"Garrett Garborcauskas","orcid":"0000-0003-0316-461X","position":6,"is_corresponding":false},{"id":52916,"name":"David R. Stirling","orcid":"0000-0001-6802-4103","position":7,"is_corresponding":false},{"id":263594,"name":"Aaron Leong","orcid":"0000-0002-3248-9547","position":8,"is_corresponding":false},{"id":730974,"name":"Katherine Figueroa","orcid":"0000-0002-6834-5668","position":9,"is_corresponding":false},{"id":13165,"name":"Nicholas A. Sinnott-Armstrong","orcid":"0000-0003-4490-0601","position":10,"is_corresponding":false},{"id":2283,"name":"Maria Kost‐Alimova","orcid":"0000-0002-5257-4909","position":11,"is_corresponding":false},{"id":807192,"name":"Giacomo Deodato","orcid":null,"position":12,"is_corresponding":false},{"id":806374,"name":"Alycen Harney","orcid":"0000-0002-7869-006X","position":13,"is_corresponding":false},{"id":301,"name":"Gregory P. Way","orcid":"0000-0002-0503-9348","position":14,"is_corresponding":false},{"id":85862,"name":"Alham Saadat","orcid":null,"position":15,"is_corresponding":false},{"id":807193,"name":"Sierra Harken","orcid":null,"position":16,"is_corresponding":false},{"id":807194,"name":"Saskia Reibe-Pal","orcid":null,"position":17,"is_corresponding":false},{"id":807195,"name":"Hannah Ebert","orcid":null,"position":18,"is_corresponding":false},{"id":806375,"name":"Yixin Zhang","orcid":"0009-0008-2528-4624","position":19,"is_corresponding":false},{"id":806376,"name":"Virtu Calabuig-Navarro","orcid":"0000-0001-6277-7040","position":20,"is_corresponding":false},{"id":31458,"name":"Elizabeth R. McGonagle","orcid":"0000-0001-9708-9272","position":21,"is_corresponding":false},{"id":31457,"name":"Adam Štefek","orcid":null,"position":22,"is_corresponding":false},{"id":1051,"name":"Josée Dupuis","orcid":"0000-0003-2871-3603","position":23,"is_corresponding":false},{"id":52924,"name":"Beth A. Cimini","orcid":"0000-0001-9640-9318","position":24,"is_corresponding":false},{"id":89433,"name":"Hans Hauner","orcid":"0000-0002-1682-5088","position":25,"is_corresponding":false},{"id":7372,"name":"Miriam S. Udler","orcid":"0000-0003-3824-9162","position":26,"is_corresponding":false},{"id":11498,"name":"Anne E. Carpenter","orcid":"0000-0003-1555-8261","position":27,"is_corresponding":false},{"id":1150,"name":"José C. Florez","orcid":"0000-0002-1730-9325","position":28,"is_corresponding":false},{"id":21993,"name":"Cecilia M. Lindgren","orcid":"0000-0002-4903-9374","position":29,"is_corresponding":false},{"id":426941,"name":"Suzanne B.R. Jacobs","orcid":"0000-0002-8103-1700","position":30,"is_corresponding":false},{"id":31471,"name":"Melina Claussnitzer","orcid":"0000-0003-2450-736X","position":31,"is_corresponding":false},{"id":31460,"name":"Samantha Laber","orcid":"0000-0002-7930-9881","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:41.672172Z","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":[]}