{"doi":"10.1101/861443","title":"Shuffle-Seq:\n                  <i>En masse</i>\n                  combinatorial encoding for\n                  <i>n</i>\n                  -way genetic interaction screens","abstract":"Genetic interactions, defined as the non-additive phenotypic impact of combinations of genes, are a hallmark of the mapping from genotype to phenotype. However, genetic interactions remain challenging to systematically test given the massive number of possible combinations. In particular, while large-scale screening efforts in yeast have quantified pairwise interactions that affect cell viability, or synthetic lethality, between all pairs of genes as well as for a limited number of three-way interactions, it has previously been intractable to perform the large screens needed to comprehensively assess interactions in a mammalian genome. Here, we develop Shuffle-Seq, a scalable method to assay genetic interactions. Shuffle-Seq leverages the co-inheritance of genetically encoded barcodes in dividing cells and can scale in proportion to sequencing throughput. We demonstrate the technical validity of Shuffle-Seq and apply it to screening for mechanisms underlying drug resistance in a melanoma model. Shuffle-Seq should allow screens of hundreds of millions of combinatorial perturbations and facilitate the understanding of genetic dependencies and drug sensitivities.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2019,"id":2456,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2019-12-02","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":7477,"name":"Olena Kuksenko","orcid":"0000-0002-1728-4957","position":1,"is_corresponding":false},{"id":29734,"name":"David Feldman","orcid":null,"position":2,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":3,"is_corresponding":false},{"id":29733,"name":"Atray Dixit","orcid":"0000-0002-5065-6492","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"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":[]}