<\/p>\n\n\n\n
Standard single-cell RNA sequencing (scRNA-seq) pipelines nearly always include unsupervised clustering as a key step in identifying biologically distinct cell types. A follow-up step in these pipelines is to test for differential expression between the identified clusters. When algorithms over-cluster, downstream analyses can produce misleading results. In this work, we present “recall” (calibrated clustering with artificial variables), a method for protecting against over-clustering by controlling for the impact of reusing the same data twice when performing differential expression analysis, commonly known as “double dipping.” Importantly, our approach can be applied to a wide range of clustering algorithms. Using real and simulated data, we show that recall provides state-of-the-art clustering performance and can rapidly analyze large-scale scRNA-seq studies, even on a personal laptop.<\/p>\n","protected":false},"excerpt":{"rendered":"
Standard single-cell RNA sequencing (scRNA-seq) pipelines nearly always include unsupervised clustering as a key step in identifying biologically distinct cell types. A follow-up step in these pipelines is to test for differential expression between the identified clusters. When algorithms over-cluster, downstream analyses can produce misleading results. In this work, we present “recall” (calibrated clustering with […]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","msr-author-ordering":[{"type":"text","value":"Alan DenAdel","user_id":0},{"type":"text","value":"Michelle L. Ramseier","user_id":0},{"type":"text","value":"Andrew W. Navia","user_id":0},{"type":"text","value":"Alex K. Shalek","user_id":0},{"type":"text","value":"Srivatsan Raghavan","user_id":0},{"type":"text","value":"Peter S. Winter","user_id":0},{"type":"user_nicename","value":"Ava Amini","user_id":"40432"},{"type":"user_nicename","value":"Lorin Crawford","user_id":"39660"}],"msr_publishername":"","msr_publisher_other":"","msr_booktitle":"","msr_chapter":"","msr_edition":"American Journal of Human Genetics","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"","msr_journal":"American journal of human genetics","msr_number":"","msr_organization":"","msr_pages_string":"","msr_page_range_start":"","msr_page_range_end":"","msr_series":"","msr_volume":"","msr_copyright":"","msr_conference_name":"","msr_doi":"10.1016\/j.ajhg.2025.02.014","msr_arxiv_id":"","msr_mag_id":"","msr_other_authors":"","msr_other_contributors":"","msr_speaker":"","msr_award":"","msr_affiliation":"","msr_institution":"","msr_host":"","msr_version":"","msr_duration":"","msr_release_tracker_id":"","msr_highlight_type":"","msr_date_display_format":"","msr_main_download_label":"","msr_external_link_label":"","msr_doi_label":"","msr_published_date":"2025-03-01","msr_startdate":"","msr_presentation_date":"","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"","msr_external_url":"","msr_secondary_video_url":"","msr_conference_url":"","msr_journal_url":"","msr_year":2025,"msr_month":3,"msr_day":1,"msr_microsoftintellectualproperty":false,"msr_pub_id":"8e4bca218c03c56032e926c09c8eb63b7393f42b","msr_publication_uploader":[{"type":"url","title":"https:\/\/pubmed.ncbi.nlm.nih.gov\/40081375","label_id":243109,"id":false,"viewUrl":false}],"msr_related_uploader":[],"msr_original_fields_of_study":[],"msr_s2_paper_id":"8e4bca218c03c56032e926c09c8eb63b7393f42b","msr_s2_pdf_url":"https:\/\/doi.org\/10.1016\/j.ajhg.2025.02.014","msr_citation_count_updated":"","msr_citation_count":5,"msr_influential_citations":0,"msr_reference_count":29,"msr_s2_open_access":true,"msr_s2_author_ids":[],"msr_pub_ids":[{"provider":"s2","id":"8e4bca218c03c56032e926c09c8eb63b7393f42b"},{"provider":"doi","id":"10.1016\/j.ajhg.2025.02.014"},{"provider":"pubmed","id":"40081375"},{"provider":"corpusid","id":"276974972"}],"msr_hide_image_in_river":0,"footnotes":""},"msr-research-highlight":[],"research-area":[13553],"msr-publication-type":[193715],"msr-publisher":[],"msr-publication-cta":[],"msr-focus-area":[],"msr-locale":[268875],"msr-post-option":[],"msr-field-of-study":[246985],"msr-conference":[],"msr-journal":[270600],"msr-impact-theme":[],"msr-pillar":[],"class_list":["post-1187501","msr-research-item","type-msr-research-item","status-publish","hentry","msr-research-area-medical-health-genomics","msr-locale-en_us","msr-field-of-study-medicine"],"msr_publishername":"","msr_edition":"American Journal of Human Genetics","msr_affiliation":"","msr_published_date":"2025-03-01","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"","msr_chapter":"","msr_isbn":"","msr_journal":"American journal of human genetics","msr_volume":"","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"","msr_organization":"","msr_how_published":"","msr_notes":"","msr_highlight_text":"","msr_release_tracker_id":"","msr_original_fields_of_study":"","msr_download_urls":"","msr_external_url":"","msr_secondary_video_url":"","msr_longbiography":"","msr_microsoftintellectualproperty":0,"msr_main_download":"","msr_publicationurl":"","msr_doi":"10.1016\/j.ajhg.2025.02.014","msr_publication_uploader":[{"type":"url","title":"https:\/\/pubmed.ncbi.nlm.nih.gov\/40081375","label_id":243109,"id":false,"viewUrl":false}],"msr_related_uploader":[],"msr_citation_count":5,"msr_citation_count_updated":"","msr_s2_paper_id":"8e4bca218c03c56032e926c09c8eb63b7393f42b","msr_influential_citations":0,"msr_reference_count":29,"msr_arxiv_id":"","msr_s2_author_ids":[],"msr_s2_open_access":true,"msr_s2_pdf_url":"https:\/\/doi.org\/10.1016\/j.ajhg.2025.02.014","msr_attachments":[],"msr-author-ordering":[{"type":"text","value":"Alan DenAdel","user_id":0,"rest_url":false},{"type":"text","value":"Michelle L. Ramseier","user_id":0,"rest_url":false},{"type":"text","value":"Andrew W. Navia","user_id":0,"rest_url":false},{"type":"text","value":"Alex K. Shalek","user_id":0,"rest_url":false},{"type":"text","value":"Srivatsan Raghavan","user_id":0,"rest_url":false},{"type":"text","value":"Peter S. Winter","user_id":0,"rest_url":false},{"type":"user_nicename","value":"Ava Amini","user_id":40432,"rest_url":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=Ava Amini"},{"type":"user_nicename","value":"Lorin Crawford","user_id":39660,"rest_url":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=Lorin Crawford"}],"msr_impact_theme":[],"msr_research_lab":[],"msr_event":[],"msr_group":[],"msr_project":[],"publication":[],"video":[],"msr-tool":[],"msr_publication_type":"article","related_content":[],"_links":{"self":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/1187501","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item"}],"about":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/types\/msr-research-item"}],"version-history":[{"count":4,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/1187501\/revisions"}],"predecessor-version":[{"id":1187524,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/1187501\/revisions\/1187524"}],"wp:attachment":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/media?parent=1187501"}],"wp:term":[{"taxonomy":"msr-research-highlight","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-highlight?post=1187501"},{"taxonomy":"msr-research-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/research-area?post=1187501"},{"taxonomy":"msr-publication-type","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publication-type?post=1187501"},{"taxonomy":"msr-publisher","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publisher?post=1187501"},{"taxonomy":"msr-publication-cta","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publication-cta?post=1187501"},{"taxonomy":"msr-focus-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-focus-area?post=1187501"},{"taxonomy":"msr-locale","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-locale?post=1187501"},{"taxonomy":"msr-post-option","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-post-option?post=1187501"},{"taxonomy":"msr-field-of-study","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-field-of-study?post=1187501"},{"taxonomy":"msr-conference","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-conference?post=1187501"},{"taxonomy":"msr-journal","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-journal?post=1187501"},{"taxonomy":"msr-impact-theme","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-impact-theme?post=1187501"},{"taxonomy":"msr-pillar","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-pillar?post=1187501"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}