ArticleNature biotechnology2024
Systematic benchmarking of single-cell ATAC-sequencing protocols.
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Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
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Who cites it
33 citing papers in PubMed.
- A guide to understanding tumour evolution through the lens of population genetics.Nature reviews. Cancer · 2026Review
- Clonal lineage tracing of innate immune cells in human cancer.Cancer cell · 2026Article
- Single-nucleus chromatin accessibility and gene expression co-profiling by ISSAAC-seq.Nature protocols · 2026Review
- Neutrophil-derived S100A8/A9 impairs megakaryocyte maturation in immune thrombocytopenia.Nature communications · 2026Article
- Beyond chromatin accessibility: bulk ATAC-seq as an integrative assay to portray genomes and epigenomes.NAR genomics and bioinformatics · 2026Article
- From histology to spatial transcriptomics: establishing a lightweight single-patch baseline.BMC bioinformatics · 2026Article
- Inferring tumor absolute copy number and clonal substructure from single-cell chromatin accessibility.Briefings in bioinformatics · 2026Article
- CREsted: modeling genomic and synthetic cell-type-specific enhancers across tissues and species.Nature methods · 2026Article
- Article
- Systematic evaluation of single-cell multimodal data integration enhances cell type resolution and discovery of clinically relevant states in complex tissues.Genome biology · 2026Article
- Evaluating single-cell ATAC-seq atlasing technologies using sequence-to-function modeling.Nature communications · 2026Article
- A hitchhiker's guide to single-cell epigenomics: Methods and applications for cancer research.International journal of cancer · 2026Review
- Advances in scCUT&Tag and computational analysis for single-cell gene regulatory element mapping.Briefings in bioinformatics · 2026Review
- Revealing a coherent cell-state landscape across single-cell datasets with CONCORD.Nature biotechnology · 2026Article
- Crosstalk between innate immune signaling pathways and integrated TLR, NLRP3 inflammasome, cGAS-STING, and NF-κB networks in sepsis.Frontiers in cell and developmental biology · 2026Review
- scFFPE-ATAC enables high-throughput single cell chromatin accessibility profiling in formalin-fixed paraffin-embedded samples.Nature communications · 2025Article
- Single-cell sequencing technology in renal cancer: insights into tumor biology and clinical application.Biomarker research · 2025Review
- Revealing a coherent cell state landscape across single cell datasets with CONCORD.bioRxiv : the preprint server for biology · 2025Article
- Chromatin accessibility provides a window into the genetic etiology of human brain disease.Trends in genetics : TIG · 2025Review
- Cell-Type Annotation for scATAC-Seq Data by Integrating Chromatin Accessibility and Genome Sequence.Biomolecules · 2025Article
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Authors and funding
45 authors.
Florian V De RopVIB Center for Brain and Disease Research, Leuven, Belgium.ORCID http://orcid.org/0000-0001-5241-924X
Gert HulselmansVIB Center for Brain and Disease Research, Leuven, Belgium.
Chris FlerinVIB Center for Brain and Disease Research, Leuven, Belgium.ORCID http://orcid.org/0000-0003-1883-871X
Paula Soler-VilaInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Albert RafelsCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Valerie ChristiaensVIB Center for Brain and Disease Research, Leuven, Belgium.
Carmen Bravo González-BlasVIB Center for Brain and Disease Research, Leuven, Belgium.
Domenica MarcheseCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Ginevra CaratùCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.ORCID http://orcid.org/0000-0003-1085-8062
Suresh PoovathingalVIB Center for Brain and Disease Research, Leuven, Belgium.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6313-3570
Michael SlyperBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Wendy LuoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7041-823X
Christoph MuusBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2779-0893
Fabiana DuarteDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1261-4929
Rojesh ShresthaDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
S Tansu BagdatliDepartment of Genetics, Stanford University, Stanford, CA, USA.
M Ryan CorcesGladstone Institute of Neurological Disease, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-7465-7652
Lira MamanovaWellcome Sanger Institute, Cambridge, UK.
Andrew KnightsWellcome Sanger Institute, Cambridge, UK.
Kerstin B MeyerWellcome Sanger Institute, Cambridge, UK.ORCID http://orcid.org/0000-0001-5906-1498
Ryan MulqueenDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0002-3903-7594
Akram TaherinasabDivision of Hematology & Medical Oncology, Knight Cancer Institute, Oregon Health & Sciences University, Portland, OR, USA.
Patrick MaschmeyerBerlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
Jörn PezoldtLaboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-7143-5691
Camille Lucie Germaine LambertLaboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Marta IglesiasCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.ORCID http://orcid.org/0000-0003-1757-7343
Sebastián R NajleCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.ORCID http://orcid.org/0000-0002-0654-9147
Zain Y DossaniVitalant Research Institute, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9264-6340
Luciano G MartelottoAdelaide Centre for Epigenetics and the South Australian Immunogenomics Cancer Institute, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
Zach BurkettDigital Biology Group, Bio-Rad, Pleasanton, CA, USA.ORCID http://orcid.org/0000-0002-5153-485X
Ronald LebofskyDigital Biology Group, Bio-Rad, Pleasanton, CA, USA.ORCID http://orcid.org/0000-0002-3728-6415
José Ignacio Martin-SuberoInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.ORCID http://orcid.org/0000-0001-8809-5195
Satish PillaiVitalant Research Institute, San Francisco, CA, USA.
Arnau Sebé-PedrósCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.ORCID http://orcid.org/0000-0002-9896-9746
Bart DeplanckeLaboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-9935-843X
Sarah A TeichmannWellcome Sanger Institute, Cambridge, UK.ORCID http://orcid.org/0000-0002-6294-6366
Leif S LudwigBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2916-2164
Theodore P BraunDivision of Hematology & Medical Oncology, Knight Cancer Institute, Oregon Health & Sciences University, Portland, OR, USA.
Andrew C AdeyDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0001-7648-8717
William J GreenleafDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1409-3095
Jason D BuenrostroDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9958-3987
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3293-3158
Stein AertsVIB Center for Brain and Disease Research, Leuven, Belgium. stein.aerts@kuleuven.be.ORCID http://orcid.org/0000-0002-8006-0315
Holger HeynCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. holger.heyn@cnag.crg.eu.ORCID http://orcid.org/0000-0002-3276-1889
Funding
VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGEDU19AI057266 · NIAID · EMORY UNIVERSITY · PI Rafi Ahmed · 2003 to 2026
$81.7MPRODUCTION CENTER FOR MAPPING REGULATORY REGIONS OF THE HUMAN GENOMEUM1HG009442 · NHGRI · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2017 to 2021
$20.1MCenter for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8MSingle-cell Mapping Center for Human Regulatory Elements and Gene ActivityUM1HG012076 · NHGRI · STANFORD UNIVERSITY · PI Michael Ryan Corces, Ansuman Satpathy · 2021 to 2026
$13.8MHigh-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4MDefining the epigentic landscape at single cell resolutionR35GM124704 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ADEY, ANDREW · 2017 to 2021
$2.3MHigh-content single-cell epigenetic technologies scalable to the human brainRF1MH128842 · NIMH · OREGON HEALTH & SCIENCE UNIVERSITY · PI ADEY, ANDREW · 2021 to 2021
$1.9MEpigenetic tools and resources for cell-type and spatial analysis of individual mammalian non-neuronal cellsR01DA047237 · NIDA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ADEY, ANDREW · 2018 to 2020
$1.7MFunctional characterization of the Alzheimer's disease EpigenomeR00AG059918 · NIA · J. DAVID GLADSTONE INSTITUTES · PI CORCES, MICHAEL RYAN · 2020 to 2022
$944kFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) 1S80920NFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) G094121NFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) G0B5619NNHGRI NIH HHS RM1 HG007735NHGRI NIH HHS UM1 HG009436NHGRI NIH HHS UM1 HG009442NHGRI NIH HHS UM1 HG012076NIAID NIH HHS U19 AI057266NIA NIH HHS R00 AG059918NIDA NIH HHS R01 DA047237NIGMS NIH HHS R35 GM124704NIMH NIH HHS RF1 MH128842Wellcome Trust
Abstract
Single-cell assay for transposase-accessible chromatin by sequencing (scATAC-seq) has emerged as a powerful tool for dissecting regulatory landscapes and cellular heterogeneity. However, an exploration of systemic biases among scATAC-seq technologies has remained absent. In this study, we benchmark the performance of eight scATAC-seq methods across 47 experiments using human peripheral blood mononuclear cells (PBMCs) as a reference sample and develop PUMATAC, a universal preprocessing pipeline, to handle the various sequencing data formats. Our analyses reveal significant differences in sequencing library complexity and tagmentation specificity, which impact cell-type annotation, genotype demultiplexing, peak calling, differential region accessibility and transcription factor motif enrichment. Our findings underscore the importance of sample extraction, method selection, data processing and total cost of experiments, offering valuable guidance for future research. Finally, our data and analysis pipeline encompasses 169,000 PBMC scATAC-seq profiles and a best practices code repository for scATAC-seq data analysis, which are freely available to extend this benchmarking effort to future protocols.
Indexed as
BenchmarkingLeukocytes, MononuclearSingle-Cell AnalysisChromatinChromatin Immunoprecipitation SequencingHigh-Throughput Nucleotide SequencingHumansSequence Analysis, DNATransposasesChromatinTransposases
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