{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:01:17Z","timestamp":1790722877386,"version":"4.1.0"},"posted":{"date-parts":[[2024,8,6]]},"group-title":"Genomics","reference-count":119,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Physiological variability in pancreatic cell type gene regulation and the impact on diabetes risk is poorly understood. In this study we mapped gene regulation in pancreatic cell types using single cell multiomic (joint RNA-seq and ATAC-seq) profiling in 28 non-diabetic donors in combination with single cell data from 35 non-diabetic donors in the Human Pancreas Analysis Program. We identified widespread associations with age, sex, BMI, and HbA1c, where gene regulatory responses were highly cell type- and phenotype-specific. In beta cells, donor age associated with hypoxia, apoptosis, unfolded protein response, and external signal-dependent transcriptional regulators, while HbA1c associated with inflammatory responses and gender with chromatin organization. We identified 10.8K loci where genetic variants were QTLs for\n                  <jats:italic>cis<\/jats:italic>\n                  regulatory element (cRE) accessibility, including 20% with lineage- or cell type-specific effects which disrupted distinct transcription factor motifs. Type 2 diabetes and glycemic trait associated variants were enriched in both phenotype- and QTL-associated beta cell cREs, whereas type 1 diabetes showed limited enrichment. Variants at 226 diabetes and glycemic trait loci were QTLs in beta and other cell types, including 40 that were statistically colocalized, and annotating target genes of colocalized QTLs revealed genes with putatively novel roles in disease. Our findings reveal diverse responses of pancreatic cell types to phenotype and genotype in physiology, and identify pathways, networks, and genes through which physiology impacts diabetes risk.\n                <\/jats:p>","DOI":"10.1101\/2024.08.03.606460","type":"posted-content","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T20:43:33Z","timestamp":1722977013000},"source":"Crossref","is-referenced-by-count":12,"title":["Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk"],"prefix":"10.64898","author":[{"given":"Hannah M","family":"Mummey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weston","family":"Elison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katha","family":"Korgaonkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth M","family":"Elgamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parul","family":"Kudtarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Benaglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8024-5854","authenticated-orcid":false,"given":"Alokkumar","family":"Jha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn E","family":"Manning Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-0510","authenticated-orcid":false,"given":"Mark I","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Preissl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1205-1844","authenticated-orcid":false,"given":"Anna L","family":"Gloyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick E","family":"MacDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle J","family":"Gaulton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024080712051248000_2024.08.03.606460v1.1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41574-020-0355-7","article-title":"Pancreatic \u03b2-cells in type 1 and type 2 diabetes mellitus: different pathways to failure","volume":"16","year":"2020","journal-title":"Nat. Rev. Endocrinol"},{"key":"2024080712051248000_2024.08.03.606460v1.2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29103"},{"key":"2024080712051248000_2024.08.03.606460v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-00443-4"},{"key":"2024080712051248000_2024.08.03.606460v1.4","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.2337\/dbi21-0036","article-title":"The \u03b2-Cell in Type 1 Diabetes Pathogenesis: A Victim of Circumstances or an Instigator of Tragic Events?","volume":"71","year":"2022","journal-title":"Diabetes"},{"key":"2024080712051248000_2024.08.03.606460v1.5","first-page":"1","article-title":"Type 1 diabetes mellitus","volume":"3","year":"2017","journal-title":"Nat. Rev. Dis. Primer"},{"key":"2024080712051248000_2024.08.03.606460v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05245-x"},{"key":"2024080712051248000_2024.08.03.606460v1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s001250100648"},{"key":"2024080712051248000_2024.08.03.606460v1.8","doi-asserted-by":"crossref","first-page":"eabo3932","DOI":"10.1126\/sciadv.abo3932","article-title":"Aging compromises human islet beta cell function and identity by decreasing transcription factor activity and inducing ER stress","volume":"8","year":"2022","journal-title":"Sci. Adv"},{"key":"2024080712051248000_2024.08.03.606460v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00852-9"},{"key":"2024080712051248000_2024.08.03.606460v1.10","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0949"},{"key":"2024080712051248000_2024.08.03.606460v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2870"},{"key":"2024080712051248000_2024.08.03.606460v1.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1317023110"},{"key":"2024080712051248000_2024.08.03.606460v1.13","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41586-021-03552-w","article-title":"Interpreting type 1 diabetes risk with genetics and single-cell epigenomics","volume":"594","year":"2021","journal-title":"Nature"},{"key":"2024080712051248000_2024.08.03.606460v1.14","doi-asserted-by":"publisher","DOI":"10.2337\/db18-2466-PUB"},{"key":"2024080712051248000_2024.08.03.606460v1.15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005694"},{"key":"2024080712051248000_2024.08.03.606460v1.16","doi-asserted-by":"crossref","first-page":"4912","DOI":"10.1038\/s41467-020-18581-8","article-title":"Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D","volume":"11","year":"2020","journal-title":"Nat. Commun"},{"key":"2024080712051248000_2024.08.03.606460v1.17","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.cels.2018.07.007","article-title":"A Chromatin Basis for Cell Lineage and Disease Risk in the Human Pancreas","volume":"7","year":"2018","journal-title":"Cell Syst"},{"key":"2024080712051248000_2024.08.03.606460v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.08.014"},{"key":"2024080712051248000_2024.08.03.606460v1.19","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.cels.2016.08.011","article-title":"A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure","volume":"3","year":"2016","journal-title":"Cell Syst"},{"key":"2024080712051248000_2024.08.03.606460v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.004"},{"key":"2024080712051248000_2024.08.03.606460v1.21","doi-asserted-by":"publisher","DOI":"10.1101\/gr.212720.116"},{"key":"2024080712051248000_2024.08.03.606460v1.22","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0405"},{"key":"2024080712051248000_2024.08.03.606460v1.23","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41588-021-00823-0","article-title":"Single-cell chromatin accessibility identifies pancreatic islet cell type\u2013 and state-specific regulatory programs of diabetes risk","volume":"53","year":"2021","journal-title":"Nat. Genet"},{"key":"2024080712051248000_2024.08.03.606460v1.24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.molmet.2019.12.006","article-title":"Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures","volume":"32","year":"2020","journal-title":"Mol. Metab"},{"key":"2024080712051248000_2024.08.03.606460v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01397-9"},{"key":"2024080712051248000_2024.08.03.606460v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.04.048"},{"key":"2024080712051248000_2024.08.03.606460v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0538-0"},{"key":"2024080712051248000_2024.08.03.606460v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLCEL.2018.06.044"},{"key":"2024080712051248000_2024.08.03.606460v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11756"},{"key":"2024080712051248000_2024.08.03.606460v1.30","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.cmet.2024.06.001","article-title":"Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease","volume":"36","year":"2024","journal-title":"Cell Metab"},{"key":"2024080712051248000_2024.08.03.606460v1.31","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1562"},{"key":"2024080712051248000_2024.08.03.606460v1.32","doi-asserted-by":"publisher","DOI":"10.1101\/2024.06.19.599613"},{"key":"2024080712051248000_2024.08.03.606460v1.33","doi-asserted-by":"publisher","DOI":"10.2337\/db19-1394-P"},{"key":"2024080712051248000_2024.08.03.606460v1.34","doi-asserted-by":"publisher","DOI":"10.1101\/2023.02.03.526994"},{"key":"2024080712051248000_2024.08.03.606460v1.35","doi-asserted-by":"crossref","first-page":"12827","DOI":"10.1038\/s41598-019-49289-5","article-title":"Phlda3 regulates beta cell survival during stress","volume":"9","year":"2019","journal-title":"Sci. Rep"},{"key":"2024080712051248000_2024.08.03.606460v1.36","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1158\/1541-7786.MCR-07-2019","article-title":"DUSP1 is controlled by p53 during the cellular response to oxidative stress","volume":"6","year":"2008","journal-title":"Mol. Cancer Res. MCR"},{"key":"2024080712051248000_2024.08.03.606460v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.11.014"},{"key":"2024080712051248000_2024.08.03.606460v1.38","doi-asserted-by":"crossref","first-page":"103473","DOI":"10.1016\/j.isci.2021.103473","article-title":"cGMP signaling pathway that modulates NF-\u03baB activation in innate immune responses","volume":"24","year":"2021","journal-title":"iScience"},{"key":"2024080712051248000_2024.08.03.606460v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4401"},{"key":"2024080712051248000_2024.08.03.606460v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"2024080712051248000_2024.08.03.606460v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3467"},{"key":"2024080712051248000_2024.08.03.606460v1.42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41588-018-0268-8","article-title":"Flexible statistical methods for estimating and testing effects in genomic studies with multiple conditions","volume":"51","year":"2019","journal-title":"Nat. Genet"},{"key":"2024080712051248000_2024.08.03.606460v1.43","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv470"},{"key":"2024080712051248000_2024.08.03.606460v1.44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004633"},{"key":"2024080712051248000_2024.08.03.606460v1.45","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0464"},{"key":"2024080712051248000_2024.08.03.606460v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09975-4"},{"key":"2024080712051248000_2024.08.03.606460v1.47","doi-asserted-by":"crossref","unstructured":"Ackeifi, C. , et al. Pharmacologic and genetic approaches define human pancreatic \u03b2 cell mitogenic targets of DYRK1A inhibitors. JCI Insight 5, (2020).","DOI":"10.1172\/jci.insight.132594"},{"key":"2024080712051248000_2024.08.03.606460v1.48","doi-asserted-by":"crossref","first-page":"5063","DOI":"10.1172\/JCI137556","article-title":"Hypoxia-inducible factors and diabetes","volume":"130","year":"2020","journal-title":"J. Clin. Invest"},{"key":"2024080712051248000_2024.08.03.606460v1.49","doi-asserted-by":"crossref","first-page":"e56227","DOI":"10.15252\/embr.202256227","article-title":"Hypoxia causes pancreatic \u03b2-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40","volume":"24","year":"2023","journal-title":"EMBO Rep"},{"key":"2024080712051248000_2024.08.03.606460v1.50","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.3390\/ijms25084186","article-title":"Roles of \u03b2-Cell Hypoxia in the Progression of Type 2 Diabetes","volume":"25","year":"2024","journal-title":"Int. J. Mol. Sci"},{"key":"2024080712051248000_2024.08.03.606460v1.51","doi-asserted-by":"publisher","DOI":"10.1007\/S00125-021-05380-Z"},{"key":"2024080712051248000_2024.08.03.606460v1.52","doi-asserted-by":"crossref","unstructured":"Cha, J. , Aguayo-Mazzucato, C. & Thompson, P. J . Pancreatic \u03b2-cell senescence in diabetes: mechanisms, markers and therapies. Front. Endocrinol. 14, (2023).","DOI":"10.3389\/fendo.2023.1212716"},{"key":"2024080712051248000_2024.08.03.606460v1.53","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1820"},{"key":"2024080712051248000_2024.08.03.606460v1.54","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1605-2"},{"key":"2024080712051248000_2024.08.03.606460v1.55","doi-asserted-by":"crossref","unstructured":"Varghese, S. S. & Dhawan, S . Senescence: a double-edged sword in beta-cell health and failure? Front. Endocrinol. 14, (2023).","DOI":"10.3389\/fendo.2023.1196460"},{"key":"2024080712051248000_2024.08.03.606460v1.56","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-019-00745-4"},{"key":"2024080712051248000_2024.08.03.606460v1.57","doi-asserted-by":"publisher","DOI":"10.4239\/WJD.V14.I3.130"},{"key":"2024080712051248000_2024.08.03.606460v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/nri2925"},{"key":"2024080712051248000_2024.08.03.606460v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.21"},{"key":"2024080712051248000_2024.08.03.606460v1.60","doi-asserted-by":"crossref","unstructured":"Rabhi, N. , Salas, E. , Froguel, P. & Annicotte, J.-S . Role of the Unfolded Protein Response in \u03b2 Cell Compensation and Failure during Diabetes. J. Diabetes Res. 2014, 795171 (2014).","DOI":"10.1155\/2014\/795171"},{"key":"2024080712051248000_2024.08.03.606460v1.61","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1210\/clinem\/dgac535","article-title":"Aging Impairs Adaptive Unfolded Protein Response and Drives Beta Cell Dedifferentiation in Humans","volume":"107","year":"2022","journal-title":"J. Clin. Endocrinol. Metab"},{"key":"2024080712051248000_2024.08.03.606460v1.62","doi-asserted-by":"crossref","first-page":"4621","DOI":"10.1038\/s41467-022-32425-7","article-title":"Adaptation to chronic ER stress enforces pancreatic \u03b2-cell plasticity","volume":"13","year":"2022","journal-title":"Nat. Commun"},{"key":"2024080712051248000_2024.08.03.606460v1.63","first-page":"37","article-title":"Beta Cell Dysfunction and Insulin Resistance","volume":"4","year":"2013","journal-title":"Front. Endocrinol"},{"key":"2024080712051248000_2024.08.03.606460v1.64","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10842"},{"key":"2024080712051248000_2024.08.03.606460v1.65","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S275898"},{"key":"2024080712051248000_2024.08.03.606460v1.66","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0023"},{"key":"2024080712051248000_2024.08.03.606460v1.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2009.08.006"},{"key":"2024080712051248000_2024.08.03.606460v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.09.016"},{"key":"2024080712051248000_2024.08.03.606460v1.69","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1210\/jc.2014-4454","article-title":"Association between Inflammation and Biological Variation in Hemoglobin A1c in U.S. Nondiabetic Adults","volume":"100","year":"2015","journal-title":"J. Clin. Endocrinol. Metab"},{"key":"2024080712051248000_2024.08.03.606460v1.70","doi-asserted-by":"publisher","DOI":"10.1080\/07853890701491034"},{"key":"2024080712051248000_2024.08.03.606460v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22922-6"},{"key":"2024080712051248000_2024.08.03.606460v1.72","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90328"},{"key":"2024080712051248000_2024.08.03.606460v1.73","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805379200"},{"key":"2024080712051248000_2024.08.03.606460v1.74","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.molmet.2019.04.007","article-title":"JUND regulates pancreatic \u03b2 cell survival during metabolic stress","volume":"25","year":"2019","journal-title":"Mol. Metab"},{"key":"2024080712051248000_2024.08.03.606460v1.75","doi-asserted-by":"crossref","first-page":"100214","DOI":"10.1016\/j.xgen.2022.100214","article-title":"Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines","volume":"2","year":"2022","journal-title":"Cell Genomics"},{"key":"2024080712051248000_2024.08.03.606460v1.76","doi-asserted-by":"crossref","first-page":"e1009531","DOI":"10.1371\/journal.pgen.1009531","article-title":"Glucocorticoid signaling in pancreatic islets modulates gene regulatory programs and genetic risk of type 2 diabetes","volume":"17","year":"2021","journal-title":"PLoS Genet"},{"key":"2024080712051248000_2024.08.03.606460v1.77","doi-asserted-by":"publisher","DOI":"10.1038\/ng.530"},{"key":"2024080712051248000_2024.08.03.606460v1.78","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1007\/s00125-016-3967-7","article-title":"Islet biology, the CDKN2A\/B locus and type 2 diabetes risk","volume":"59","year":"2016","journal-title":"Diabetologia"},{"key":"2024080712051248000_2024.08.03.606460v1.79","doi-asserted-by":"publisher","DOI":"10.1038\/ng.609"},{"key":"2024080712051248000_2024.08.03.606460v1.80","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2880"},{"key":"2024080712051248000_2024.08.03.606460v1.81","doi-asserted-by":"crossref","unstructured":"Yamamoto, S. , Yabuki, R. & Kitagawa, D . Biophysical and biochemical properties of Deup1 self-assemblies: a potential driver for deuterosome formation during multiciliogenesis. Biol. Open 10, bio056432 (2021).","DOI":"10.1242\/bio.056432"},{"key":"2024080712051248000_2024.08.03.606460v1.82","doi-asserted-by":"crossref","unstructured":"Pablos, M. et al. Primary Cilia in Pancreatic \u03b2- and \u03b1-Cells: Time to Revisit the Role of Insulin-Degrading Enzyme. Front. Endocrinol. 13, (2022).","DOI":"10.3389\/fendo.2022.922825"},{"key":"2024080712051248000_2024.08.03.606460v1.83","doi-asserted-by":"crossref","first-page":"474","DOI":"10.2337\/db23-0150","article-title":"Overexpression of UBE2E2 in Mouse Pancreatic \u03b2-Cells Leads to Glucose Intolerance via Reduction of \u03b2-Cell Mass","volume":"73","year":"2024","journal-title":"Diabetes"},{"key":"2024080712051248000_2024.08.03.606460v1.84","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0524-6"},{"key":"2024080712051248000_2024.08.03.606460v1.85","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.30"},{"key":"2024080712051248000_2024.08.03.606460v1.86","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp474"},{"key":"2024080712051248000_2024.08.03.606460v1.87","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.05.004"},{"key":"2024080712051248000_2024.08.03.606460v1.88","doi-asserted-by":"crossref","unstructured":"Kulkarni, A. , Muralidharan, C. , May, S. C. , Tersey, S. A. & Mirmira, R. G . Inside the \u03b2 Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis. Endocrinology 164, bqac184 (2022).","DOI":"10.1210\/endocr\/bqac184"},{"key":"2024080712051248000_2024.08.03.606460v1.89","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.jcjd.2021.03.007","article-title":"A New Hypothesis for Type 1 Diabetes Risk: The At-Risk Allele at rs3842753 Associates With Increased Beta-Cell INS Messenger RNA in a Meta-Analysis of Single-Cell RNA-Sequencing Data","volume":"45","year":"2021","journal-title":"Can. J. Diabetes"},{"key":"2024080712051248000_2024.08.03.606460v1.90","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01087-y"},{"key":"2024080712051248000_2024.08.03.606460v1.91","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"2024080712051248000_2024.08.03.606460v1.92","doi-asserted-by":"crossref","unstructured":"Young, M. D. & Behjati, S . SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data. GigaScience 9, giaa151 (2020).","DOI":"10.1093\/gigascience\/giaa151"},{"key":"2024080712051248000_2024.08.03.606460v1.93","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s13059-021-02469-x","article-title":"AMULET: a novel read count-based method for effective multiplet detection from single nucleus ATAC-seq data","volume":"22","year":"2021","journal-title":"Genome Biol"},{"key":"2024080712051248000_2024.08.03.606460v1.94","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","article-title":"Scrublet: Computational Identification of Cell Doublets in Single-Cell Transcriptomic Data","volume":"8","year":"2019","journal-title":"Cell Syst"},{"key":"2024080712051248000_2024.08.03.606460v1.95","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"2024080712051248000_2024.08.03.606460v1.96","unstructured":"McInnes, L. , Healy, J. & Melville, J. UMAP : Uniform Manifold Approximation and Projection for Dimension Reduction. ArXiv180203426 Cs Stat (2020)."},{"key":"2024080712051248000_2024.08.03.606460v1.97","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"2024080712051248000_2024.08.03.606460v1.98","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"2024080712051248000_2024.08.03.606460v1.99","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41695-z"},{"key":"2024080712051248000_2024.08.03.606460v1.100","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"2024080712051248000_2024.08.03.606460v1.101","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt730"},{"key":"2024080712051248000_2024.08.03.606460v1.102","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0241-6"},{"key":"2024080712051248000_2024.08.03.606460v1.103","unstructured":"Signorell, A. et al. DescTools: Tools for Descriptive Statistics. (2024)."},{"key":"2024080712051248000_2024.08.03.606460v1.104","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx987"},{"key":"2024080712051248000_2024.08.03.606460v1.105","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2024080712051248000_2024.08.03.606460v1.106","unstructured":"Meta-Analysis with R | SpringerLink. https:\/\/link.springer.com\/book\/10.1007\/978-3-319-21416-0."},{"key":"2024080712051248000_2024.08.03.606460v1.107","doi-asserted-by":"publisher","DOI":"10.1101\/060012"},{"key":"2024080712051248000_2024.08.03.606460v1.108","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.cmet.2022.09.013","article-title":"Understanding islet dysfunction in type 2 diabetes through multidimensional pancreatic phenotyping: The Human Pancreas Analysis Program","volume":"34","year":"2022","journal-title":"Cell Metab"},{"key":"2024080712051248000_2024.08.03.606460v1.109","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2024080712051248000_2024.08.03.606460v1.110","unstructured":"Schep, A. motifmatchr: Fast Motif Matching in R."},{"key":"2024080712051248000_2024.08.03.606460v1.111","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"2024080712051248000_2024.08.03.606460v1.112","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"2024080712051248000_2024.08.03.606460v1.113","doi-asserted-by":"crossref","first-page":"e1010759","DOI":"10.1371\/journal.pgen.1010759","article-title":"Mapping genetic effects on cell type-specific chromatin accessibility and annotating complex immune trait variants using single nucleus ATAC-seq in peripheral blood","volume":"19","year":"2023","journal-title":"PLOS Genet"},{"key":"2024080712051248000_2024.08.03.606460v1.114","unstructured":"Shannon, P. & Richards, M. MotifDb: An Annotated Collection of Protein-DNA Binding Sequence Motifs. (2023)."},{"key":"2024080712051248000_2024.08.03.606460v1.115","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01058-3"},{"key":"2024080712051248000_2024.08.03.606460v1.116","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv402"},{"key":"2024080712051248000_2024.08.03.606460v1.117","doi-asserted-by":"crossref","unstructured":"Myers, T. A. , Chanock, S. J. & Machiela, M. J . LDlinkR: An R Package for Rapidly Calculating Linkage Disequilibrium Statistics in Diverse Populations. Front. Genet. 11, (2020).","DOI":"10.3389\/fgene.2020.00157"},{"key":"2024080712051248000_2024.08.03.606460v1.118","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts163"},{"key":"2024080712051248000_2024.08.03.606460v1.119","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.08.03.606460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:48:58Z","timestamp":1768459738000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.08.03.606460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":119,"URL":"https:\/\/doi.org\/10.1101\/2024.08.03.606460","relation":{},"subject":[],"published":{"date-parts":[[2024,8,6]]},"subtype":"preprint"}}