{"doi":"10.1101/2021.03.18.431004","title":"Micro-region transcriptomics of fixed human tissue using Pick-Seq","abstract":"ABSTRACT Spatial transcriptomics and multiplexed imaging are complementary methods for studying tissue biology and disease. Recently developed spatial transcriptomic methods use fresh-frozen specimens but most diagnostic specimens, clinical trials, and tissue archives rely on formaldehyde-fixed tissue. Here we describe the Pick-Seq method for deep spatial transcriptional profiling of fixed tissue. Pick-Seq is a form of micro-region sequencing in which small regions of tissue, containing 5-20 cells, are mechanically isolated on a microscope and then sequenced. We demonstrate the use of Pick-Seq with several different fixed and frozen human specimens. Application of Pick-Seq to a human melanoma with complex histology reveals significant differences in transcriptional programs associated with tumor invasion, proliferation, and immuno-editing. Parallel imaging confirms changes in immuno-phenotypes and cancer cell states. This work demonstrates the ability of Pick-Seq to generate deep spatial transcriptomic data from fixed and archival tissue with multiplexed imaging in parallel.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":213759,"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":0.9553,"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":621265,"name":"Ajit J. Nirmal","orcid":"0000-0003-4139-0618","position":1,"is_corresponding":false},{"id":56445,"name":"Nolan G. Ericson","orcid":"0000-0002-2985-3221","position":2,"is_corresponding":false},{"id":268857,"name":"Sarah A. Boswell","orcid":"0000-0002-3118-3378","position":3,"is_corresponding":false},{"id":807166,"name":"Lance U’Ren","orcid":null,"position":4,"is_corresponding":false},{"id":807167,"name":"Rebecca Podyminogin","orcid":null,"position":5,"is_corresponding":false},{"id":376937,"name":"Jennifer Chow","orcid":"0000-0002-4800-7979","position":6,"is_corresponding":false},{"id":459620,"name":"Yu‐An Chen","orcid":"0000-0001-7228-4696","position":7,"is_corresponding":false},{"id":225137,"name":"Alyce A. Chen","orcid":"0000-0002-5018-8908","position":8,"is_corresponding":false},{"id":30187,"name":"David M. Weinstock","orcid":"0000-0002-8724-3907","position":9,"is_corresponding":false},{"id":40506,"name":"Christine G. Lian","orcid":"0000-0003-4626-1612","position":10,"is_corresponding":false},{"id":40507,"name":"Gëorge F. Murphy","orcid":"0000-0001-9362-5146","position":11,"is_corresponding":false},{"id":807168,"name":"Eric Kaldjian","orcid":null,"position":12,"is_corresponding":false},{"id":70392,"name":"Sandro Santagata","orcid":"0000-0002-7528-9668","position":13,"is_corresponding":false},{"id":24147,"name":"Peter K. Sorger","orcid":"0000-0002-3364-1838","position":14,"is_corresponding":false},{"id":70934,"name":"Zoltan Maliga","orcid":"0000-0003-4209-7253","position":0,"is_corresponding":true}],"reference_count":46,"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":[]}