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Here, we present Quality Clustering (QClus), a droplet filtering algorithm targeted toward challenging samples. QClus uses additional metrics, such as cell-type-specific marker gene expression, to cluster nuclei and filter empty and highly contaminated droplets, providing reliable filtering of samples with varying number of nuclei and contamination levels. In a benchmarking analysis against seven alternative methods across six datasets, consisting of 252 samples and over 1.9 million nuclei, QClus achieved the highest quality in the greatest number of samples over all evaluated quality metrics and recorded no processing failures, while robustly retaining numbers of nuclei within the expected range. QClus combines high quality, automation and robustness with flexibility and user-adjustability, catering to diverse experimental needs and datasets.<\/jats:p>","DOI":"10.1093\/nar\/gkae1145","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T15:23:40Z","timestamp":1730733820000},"source":"Crossref","is-referenced-by-count":6,"title":["QClus: a droplet filtering algorithm for enhanced snRNA-seq data quality in challenging samples"],"prefix":"10.1093","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2123-8777","authenticated-orcid":false,"given":"Eloi","family":"Schmauch","sequence":"first","affiliation":[{"name":"Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology , 32 Vassar St, Cambridge , MA 02139 ,","place":["USA"]},{"name":"Broad Institute of MIT and Harvard , 415 Main Street, Cambridge , MA 02142 ,","place":["USA"]},{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland , Neulaniementie 2, 70211 Kuopio ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Ojanen","sequence":"additional","affiliation":[{"name":"Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology , 32 Vassar St, Cambridge , MA 02139 ,","place":["USA"]},{"name":"Broad Institute of MIT and Harvard , 415 Main Street, Cambridge , MA 02142 ,","place":["USA"]},{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland , Neulaniementie 2, 70211 Kuopio ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriakitsa","family":"Galani","sequence":"additional","affiliation":[{"name":"Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology , 32 Vassar St, Cambridge , MA 02139 ,","place":["USA"]},{"name":"Broad Institute of MIT and Harvard , 415 Main Street, Cambridge , MA 02142 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juho","family":"Jalkanen","sequence":"additional","affiliation":[{"name":"Medicity Research Laboratories, University of Turku , Tykist\u00f6katu 6, 20520 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristiina","family":"Harju","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland , Neulaniementie 2, 70211 Kuopio ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maija","family":"Hollm\u00e9n","sequence":"additional","affiliation":[{"name":"Medicity Research Laboratories, University of Turku , Tykist\u00f6katu 6, 20520 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannu","family":"Kokki","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Operative Services, Kuopio University Hospital , Puijonlaaksontie 2, 70029 KYS,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarmo","family":"Gunn","sequence":"additional","affiliation":[{"name":"Heart Center, Turku University Hospital , H\u00e4meentie 11, 20521 Turku ,","place":["Finland"]},{"name":"Department of Medicine, University of Turku , Kiinamyllynkatu 10, 20520 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3878-1546","authenticated-orcid":false,"given":"Jari","family":"Halonen","sequence":"additional","affiliation":[{"name":"Medical School, University of Eastern Finland , Yliopistonranta 8, 70210 Kuopio ,","place":["Finland"]},{"name":"Heart Center, Kuopio University Hospital , Puijonlaaksontie 2, 70211 Kuopio ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Hartikainen","sequence":"additional","affiliation":[{"name":"Medical School, University of Eastern Finland , Yliopistonranta 8, 70210 Kuopio ,","place":["Finland"]},{"name":"Heart Center, Kuopio University Hospital , Puijonlaaksontie 2, 70211 Kuopio ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-3741","authenticated-orcid":false,"given":"Tuomas","family":"Kiviniemi","sequence":"additional","affiliation":[{"name":"Heart Center, Turku University Hospital , H\u00e4meentie 11, 20521 Turku ,","place":["Finland"]},{"name":"Department of Medicine, University of Turku , Kiinamyllynkatu 10, 20520 Turku ,","place":["Finland"]},{"name":"Cardiovascular Medicine and Network Medicine Division, Brigham and Women\u2019s Hospital, Harvard Medical School ,\u00a075 Francis St, Boston , MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-3616","authenticated-orcid":false,"given":"Pasi","family":"Tavi","sequence":"additional","affiliation":[{"name":"A. 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