{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:18:15Z","timestamp":1785406695713,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,22]]},"group-title":"Immunology","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R01AR082203"],"award-info":[{"award-number":["1R01AR082203"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5T32AR007107"],"award-info":[{"award-number":["5T32AR007107"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR078334"],"award-info":[{"award-number":["AR078334"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03sdr0263","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Elli Lilly and Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Systemic lupus erythematosus (SLE or lupus) is an autoimmune disease characterized by anti-nuclear antibody (ANA) production and inflammation, though the mechanisms by which ANAs induce inflammation and tissue injury are incompletely understood. Here, we identified distinct subsets of mononuclear phagocytes (MPs), including monocytes (Mo) and macrophages (M\u03a6), driven by lupus immune complex (IC), comprised of ANAs and their target antigens. scRNA-seq of human Mo incubated with U1-snRNP (snRNP) lupus IC revealed expansion of distinct pro-inflammatory Mo subsets with upregulation of inflammatory genes including those encoding cytokines, NLRP3, and transcription factors. These transcriptomic changes strongly correlated with protein expression, as determined by proteomic analysis. Mo developed similar pro-inflammatory transcriptomic changes in response to other lupus ICs containing anti-dsDNA and Ro60 antibodies. Interrogation of scRNA-seq datasets from the skin, kidney, and peripheral blood of lupus patients revealed the presence and expansion of pro-inflammatory Mo and M\u03a6 populations exhibiting transcriptomic signatures similar to those observed in lupus IC-stimulated Mo. Some of these cells expressing the snRNP IC gene signature exhibited low expression of the type I IFN signature, suggesting that lupus IC and type I IFN signaling may independently affect Mo subsets. In lupus nephritis, infiltration of CD68+ M\u03a6 expressing NLRP3 was associated with treatment outcomes. Inhibiting activation of the transcription factor ETS2, a master regulator of Mo\/M\u03a6-driven inflammation, attenuated lupus IC-induced activation of pro-inflammatory Mo. Collectively, these findings provide novel insights into the role of lupus IC-driven pro-inflammatory MPs in the pathogenesis of SLE and highlight their relevance as therapeutic targets.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>Systemic lupus erythematosus (SLE or lupus) is a multi-systemic autoimmune inflammatory disease characterized by anti-nuclear antibody (ANA) production. Lupus immune complex (IC), consisting of ANAs and their target antigens, likely play a critical role in the pathogenesis of lupus through activation of mononuclear phagocytes (MPs), including monocytes (Mo) and macrophages (M\u03a6), which can produce an array of inflammatory molecules. Using transcriptomic and proteomic analyses, our study identified distinct pro-inflammatory Mo populations driven by lupus IC, along with expansion of similar pro-inflammatory Mo and M\u03a6 subsets in the skin, kidneys, and peripheral blood of lupus patients. These findings provide novel insights into the pathogenic role of lupus IC-driven pro-inflammatory MPs and support a scientific rationale for therapeutically targeting these cells.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"700902v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.21.700902","type":"posted-content","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:45:17Z","timestamp":1769125517000},"source":"Crossref","is-referenced-by-count":0,"title":["Lupus Immune Complexes Drive Distinct Pro-Inflammatory Monocyte and Macrophage Populations Independent of Type I Interferon"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-390X","authenticated-orcid":false,"given":"Lais","family":"Osmani","sequence":"first","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"},{"name":"Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea 41944"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Jae","family":"Seong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoungsu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"},{"name":"Department of Internal Medicine, Hallym University School of Medicine, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea 05355"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongjin","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"},{"name":"Department of Internal Medicine, Hallym University School of Medicine, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea 05355"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Bracamonte","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8586-8326","authenticated-orcid":false,"given":"Mario","family":"Felix","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Gyun","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"},{"name":"Department of Pediatrics, Severance Children\u2019s Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 03722"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Jai","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junghee J","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serhan","family":"Unlu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennefer","family":"Par-Young","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Doherty","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Public Health, Yale Graduate School of Arts and Sciences, New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei X","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotios","family":"Koumpouras","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Pulmonary, Critical Care & Sleep Medicine), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5917-4601","authenticated-orcid":false,"given":"Naftali","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Pulmonary, Critical Care & Sleep Medicine), Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5783-5736","authenticated-orcid":false,"given":"Richard","family":"Bucala","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"},{"name":"Department of Pathology, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungyong","family":"You","sequence":"additional","affiliation":[{"name":"Departments of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7483-1171","authenticated-orcid":false,"given":"Insoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT 06520"},{"name":"Department of Pathology, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050722181137000_2026.01.21.700902v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.05.006"},{"key":"2026050722181137000_2026.01.21.700902v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3671"},{"key":"2026050722181137000_2026.01.21.700902v2.3","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad069"},{"key":"2026050722181137000_2026.01.21.700902v2.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204289119"},{"key":"2026050722181137000_2026.01.21.700902v2.5","doi-asserted-by":"crossref","unstructured":"W.-T. Ma , F. Gao , K. Gu , D.-K. Chen , The Role of Monocytes and Macrophages in Autoimmune Diseases: A Comprehensive Review. Front Immunol 10, 1140 (2019).","DOI":"10.3389\/fimmu.2019.01140"},{"key":"2026050722181137000_2026.01.21.700902v2.6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103355"},{"key":"2026050722181137000_2026.01.21.700902v2.7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201195"},{"key":"2026050722181137000_2026.01.21.700902v2.8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/art.40672","article-title":"Macrophage Migration Inhibitory Factor Regulates U1 Small Nuclear RNP Immune Complex\u2013Mediated Activation of the NLRP3 Inflammasome","volume":"71","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"2026050722181137000_2026.01.21.700902v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.07.013"},{"key":"2026050722181137000_2026.01.21.700902v2.10","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1172\/JCI125116","article-title":"Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis","volume":"129","year":"2019","journal-title":"J Clin Invest"},{"key":"2026050722181137000_2026.01.21.700902v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04642-z"},{"key":"2026050722181137000_2026.01.21.700902v2.12","doi-asserted-by":"crossref","first-page":"e157272","DOI":"10.1172\/JCI157272","article-title":"NLRP12 is an innate immune checkpoint for repressing IFN signatures and attenuating lupus nephritis progression","volume":"133","year":"2023","journal-title":"Journal of Clinical Investigation"},{"key":"2026050722181137000_2026.01.21.700902v2.13","doi-asserted-by":"crossref","unstructured":"P. Badia-i-Mompel , et al., decoupleR: ensemble of computational methods to infer biological activities from omics data. Bioinformatics Advances 2, vbac016 (2022).","DOI":"10.1093\/bioadv\/vbac016"},{"key":"2026050722181137000_2026.01.21.700902v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07501-1"},{"key":"2026050722181137000_2026.01.21.700902v2.15","doi-asserted-by":"crossref","unstructured":"L. Faure , R. Soldatov , P. V. Kharchenko , I. Adameyko , scFates: a scalable python package for advanced pseudotime and bifurcation analysis from single-cell data. Bioinformatics 39, btac746 (2023).","DOI":"10.1093\/bioinformatics\/btac746"},{"key":"2026050722181137000_2026.01.21.700902v2.16","doi-asserted-by":"crossref","unstructured":"D. Giordano , et al., B cell-activating factor (BAFF) from dendritic cells, monocytes and neutrophils is required for B cell maturation and autoantibody production in SLE-like autoimmune disease. Front. Immunol. 14, 1050528 (2023).","DOI":"10.3389\/fimmu.2023.1050528"},{"key":"2026050722181137000_2026.01.21.700902v2.17","doi-asserted-by":"crossref","first-page":"e156341","DOI":"10.1172\/jci.insight.156341","article-title":"Single-cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney","volume":"7","year":"2022","journal-title":"JCI Insight"},{"key":"2026050722181137000_2026.01.21.700902v2.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0398-x"},{"key":"2026050722181137000_2026.01.21.700902v2.19","doi-asserted-by":"crossref","unstructured":"R. K. Perez , et al., Single-cell RNA-seq reveals cell type-specific molecular and genetic associations to lupus. Science 376, eabf1970 (2022).","DOI":"10.1126\/science.abf1970"},{"key":"2026050722181137000_2026.01.21.700902v2.20","doi-asserted-by":"crossref","unstructured":"S. J. Lee , et al., Investigating cytotoxic and inflammatory human IL-7 receptor low effector memory CD8+ T cells in lupus. EBioMedicine 119, 105898 (2025).","DOI":"10.1016\/j.ebiom.2025.105898"},{"key":"2026050722181137000_2026.01.21.700902v2.21","doi-asserted-by":"crossref","unstructured":"S. Jin , M. V. Plikus , Q. Nie , CellChat for systematic analysis of cell-cell communication from single-cell and spatially resolved transcriptomics. [Preprint] (2023). Available at: http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.11.05.565674 [Accessed 16 July 2024].","DOI":"10.1101\/2023.11.05.565674"},{"key":"2026050722181137000_2026.01.21.700902v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06311-1"},{"key":"2026050722181137000_2026.01.21.700902v2.23","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.24.10954-10964.2004"},{"key":"2026050722181137000_2026.01.21.700902v2.24","doi-asserted-by":"publisher","DOI":"10.1086\/646616"},{"key":"2026050722181137000_2026.01.21.700902v2.25","doi-asserted-by":"crossref","unstructured":"D. Oikawa , et al., OTUD1 deubiquitinase regulates NF-\u03baB- and KEAP1-mediated inflammatory responses and reactive oxygen species-associated cell death pathways. Cell Death Dis 13, 694 (2022).","DOI":"10.1038\/s41419-022-05145-5"},{"key":"2026050722181137000_2026.01.21.700902v2.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.04.004"},{"key":"2026050722181137000_2026.01.21.700902v2.27","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12308"},{"key":"2026050722181137000_2026.01.21.700902v2.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912116107"},{"key":"2026050722181137000_2026.01.21.700902v2.29","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-324855"},{"key":"2026050722181137000_2026.01.21.700902v2.30","doi-asserted-by":"crossref","unstructured":"V. Garcia , Y. R. Perera , W. J. Chazin , A Structural Perspective on Calprotectin as a Ligand of Receptors Mediating Inflammation and Potential Drug Target. Biomolecules 12, 519 (2022).","DOI":"10.3390\/biom12040519"},{"key":"2026050722181137000_2026.01.21.700902v2.31","doi-asserted-by":"crossref","unstructured":"P. Singh , S. A. Ali , Multifunctional Role of S100 Protein Family in the Immune System: An Update. Cells 11, 2274 (2022).","DOI":"10.3390\/cells11152274"},{"key":"2026050722181137000_2026.01.21.700902v2.32","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1177\/0961203316655208","article-title":"Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus","volume":"26","year":"2017","journal-title":"Lupus"},{"key":"2026050722181137000_2026.01.21.700902v2.33","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/art.43017","article-title":"Urinary Biomarkers Associated With Pathogenic Pathways Reflecting Histologic Findings in Lupus Nephritis","volume":"77","year":"2025","journal-title":"Arthritis Rheumatol"},{"key":"2026050722181137000_2026.01.21.700902v2.34","doi-asserted-by":"crossref","unstructured":"M. Mussbacher , M. Derler , J. Bas\u00edlio , J. A. Schmid , NF-\u03baB in monocytes and macrophages \u2013 an inflammatory master regulator in multitalented immune cells. Front. Immunol. 14, 1134661 (2023).","DOI":"10.3389\/fimmu.2023.1134661"},{"key":"2026050722181137000_2026.01.21.700902v2.35","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2013.78.021246"},{"key":"2026050722181137000_2026.01.21.700902v2.36","doi-asserted-by":"crossref","unstructured":"S. L. Enoksson , et al., The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells. Proc. Natl. Acad. Sci. U.S.A. 108 (2011).","DOI":"10.1073\/pnas.1107830108"},{"key":"2026050722181137000_2026.01.21.700902v2.37","doi-asserted-by":"crossref","unstructured":"R. Mende , et al., Analysis of Serum Interleukin (IL)-1\u03b2 and IL-18 in Systemic Lupus Erythematosus. Front. Immunol. 9, 1250 (2018).","DOI":"10.3389\/fimmu.2018.01250"},{"key":"2026050722181137000_2026.01.21.700902v2.38","doi-asserted-by":"crossref","unstructured":"C. B. Oliveira , C. A. D. Lima , G. Vajgel , P. Sandrin-Garcia , The Role of NLRP3 Inflammasome in Lupus Nephritis. IJMS 22, 12476 (2021).","DOI":"10.3390\/ijms222212476"},{"key":"2026050722181137000_2026.01.21.700902v2.39","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1002\/art.40155","article-title":"Podocyte Activation of NLRP3 Inflammasomes Contributes to the Development of Proteinuria in Lupus Nephritis","volume":"69","year":"2017","journal-title":"Arthritis & Rheumatology"},{"key":"2026050722181137000_2026.01.21.700902v2.40","doi-asserted-by":"crossref","unstructured":"X. Zhang , et al., Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review). Int J Mol Med 51, 35 (2023).","DOI":"10.3892\/ijmm.2023.5238"},{"key":"2026050722181137000_2026.01.21.700902v2.41","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/art.40930","article-title":"European League Against Rheumatism\/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus","volume":"71","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"2026050722181137000_2026.01.21.700902v2.42","unstructured":"G. X. Y. Zheng , et al., Massively parallel digital transcriptional profiling of single cells. Nat Commun 8, 14049 (2017)."},{"key":"2026050722181137000_2026.01.21.700902v2.43","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.04.048"},{"key":"2026050722181137000_2026.01.21.700902v2.44","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/19.2.185"},{"key":"2026050722181137000_2026.01.21.700902v2.45","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts034"},{"key":"2026050722181137000_2026.01.21.700902v2.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508647102"},{"key":"2026050722181137000_2026.01.21.700902v2.47","doi-asserted-by":"crossref","unstructured":"J. D. Storey , R. Tibshirani , \u201cStatistical Methods for Identifying Differentially Expressed Genes in DNA Microarrays\u201d in Functional Genomics, (Humana Press, 2003), pp. 149\u2013158.","DOI":"10.1385\/1-59259-364-X:149"},{"key":"2026050722181137000_2026.01.21.700902v2.48","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"2026050722181137000_2026.01.21.700902v2.49","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"2026050722181137000_2026.01.21.700902v2.50","doi-asserted-by":"publisher","DOI":"10.2307\/2346101"},{"key":"2026050722181137000_2026.01.21.700902v2.51","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"2026050722181137000_2026.01.21.700902v2.52","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"2026050722181137000_2026.01.21.700902v2.53","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","article-title":"Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences","volume":"4","year":"2015","journal-title":"F1000Res"},{"key":"2026050722181137000_2026.01.21.700902v2.54","doi-asserted-by":"crossref","unstructured":"M. I. Love , W. Huber , S. Anders , Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550 (2014).","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026050722181137000_2026.01.21.700902v2.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"2026050722181137000_2026.01.21.700902v2.56","first-page":"1","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","year":"2021","journal-title":"Innovation (Camb"},{"key":"2026050722181137000_2026.01.21.700902v2.57","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1381-1"},{"key":"2026050722181137000_2026.01.21.700902v2.58","doi-asserted-by":"crossref","unstructured":"M. Waskom, seaborn: statistical data visualization. JOSS 6, 3021 (2021).","DOI":"10.21105\/joss.03021"},{"key":"2026050722181137000_2026.01.21.700902v2.59","doi-asserted-by":"publisher","DOI":"10.2307\/2282330"},{"key":"2026050722181137000_2026.01.21.700902v2.60","unstructured":"A. Kassambara , ggpubr: \u201cggplot2\u201d Based Publication Ready Plots."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.01.21.700902","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:18:36Z","timestamp":1778217516000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.01.21.700902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":60,"URL":"https:\/\/doi.org\/10.64898\/2026.01.21.700902","relation":{},"subject":[],"published":{"date-parts":[[2026,1,22]]},"subtype":"preprint"}}