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Although immune tolerance is critical for pregnancy success, the specific immune dysregulations contributing to RPL, particularly in euploid pregnancies, have been difficult to characterize. To address this, we performed single-cell RNA sequencing of decidual tissues from RPL patients and first-trimester controls. Our analysis initially revealed elevated expression of a transcriptional module of immune activation genes in RPL decidual tissues. To dissect the cellular drivers of this complex landscape, we employed genotype-based origin analysis coupled with a supervised machine learning model and a transformer-based foundation model (scGPT). This hierarchical approach prioritized maternal T cells over other immune subsets as the population carrying the most distinct and generalizable RPL-associated signatures. Through the convergence of computational drug repurposing, network centrality analysis, and a rigorous origin-controlled expression filtering strategy, we identified CXCR4 and JUN as druggable molecular candidates strongly associated with this T-cell dysregulation. Collectively, our machine learning\u2013driven approach characterizes the maternal immune landscape of euploid RPL in the context of immune tolerance breakdown, and nominates candidate targets for future functional investigation.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014806","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:38:28Z","timestamp":1789666708000},"page":"e1014806","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine learning\u2013driven decoding of maternal immune signatures in repeated pregnancy loss"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2996-7975","authenticated-orcid":true,"given":"Tae Lyun","family":"Ko","sequence":"first","affiliation":[{"name":"Center for Biomedical Computing, Korea Institute of Science and Technology Information (KISTI)","place":["Daejeon, Republic of Korea"],"department":["Department of Data and HPC Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaesub","family":"Park","sequence":"additional","affiliation":[{"name":"Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea, and Cambridge Stem Cell Institute, University of Cambridge","place":["Cambridge, United Kingdom"],"department":["Department of Bio and Brain Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongju","family":"Leem","sequence":"additional","affiliation":[{"name":"Sungkyunkwan University","place":["Suwon, Republic of Korea"],"department":["Department of Biological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junho","family":"Kim","sequence":"additional","affiliation":[{"name":"Sungkyunkwan University","place":["Suwon, Republic of Korea"],"department":["Department of Biological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae won","family":"Han","sequence":"additional","affiliation":[{"name":"College of Medicine, Myunggok Medical Research Institute, Konyang University","place":["Daejeon, Republic of Korea"],"department":["Department of Obstetrics and Gynecology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Sol","family":"Park","sequence":"additional","affiliation":[{"name":"College of Medicine, Myunggok Medical Research Institute, Konyang University","place":["Daejeon, Republic of Korea"],"department":["Department of Obstetrics and Gynecology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Ki","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Medicine, Myunggok Medical Research Institute, Konyang University","place":["Daejeon, Republic of Korea"],"department":["Department of Obstetrics and Gynecology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-0670","authenticated-orcid":true,"given":"Hyojung","family":"Paik","sequence":"additional","affiliation":[{"name":"Center for Biomedical Computing, Korea Institute of Science and Technology Information (KISTI)","place":["Daejeon, Republic of Korea"],"department":["Department of Data and HPC Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"issue":"3","key":"pcbi.1014806.ref001","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1093\/humupd\/dmz048","article-title":"Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? 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Am J Reprod Immunol N Y N 1989","volume":"48","author":"F Ietta","year":"2002"},{"issue":"3","key":"pcbi.1014806.ref039","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1095\/biolreprod.110.088195","article-title":"IGF2 actions on trophoblast in human placenta are regulated by the insulin-like growth factor 2 receptor, which can function as both a signaling and clearance receptor","volume":"84","author":"LK Harris","year":"2011","journal-title":"Biol Reprod"},{"issue":"1","key":"pcbi.1014806.ref040","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jri.2009.11.008","article-title":"Human chorionic gonadotropin: a hormone with immunological and angiogenic properties","volume":"85","author":"M Tsampalas","year":"2010","journal-title":"J Reprod Immunol"},{"issue":"1","key":"pcbi.1014806.ref041","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1186\/s12935-022-02749-x","article-title":"SPP1 facilitates cell migration and invasion by targeting COL11A1 in lung adenocarcinoma","volume":"22","author":"X Yi","year":"2022","journal-title":"Cancer Cell Int"},{"issue":"1","key":"pcbi.1014806.ref042","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1038\/s41467-022-33045-x","article-title":"devCellPy is a machine learning-enabled pipeline for automated annotation of complex multilayered single-cell transcriptomic data","volume":"13","author":"FX Galdos","year":"2022","journal-title":"Nat Commun"},{"issue":"11","key":"pcbi.1014806.ref043","article-title":"Single-cell transcriptome analysis reveals defective decidua stromal niche attributes to recurrent spontaneous abortion","volume":"54","author":"L Du","year":"2021","journal-title":"Cell Prolif"},{"key":"pcbi.1014806.ref044","unstructured":"Lundberg SM, Lee SI. A unified approach to interpreting model predictions. In: Proceedings of the 31st International Conference on Neural Information Processing Systems. Red Hook, NY, USA: Curran Associates Inc.; 2017. p. 4768\u201377. (NIPS\u201917)."},{"issue":"10","key":"pcbi.1014806.ref045","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0139939","article-title":"A Unique Expression of Keratin 14 in a Subset of Trophoblast Cells. Milstone DS, editor","volume":"10","author":"W Abou-Kheir","year":"2015","journal-title":"PLOS ONE"},{"issue":"8","key":"pcbi.1014806.ref046","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/s41592-024-02201-0","article-title":"scGPT: toward building a foundation model for single-cell multi-omics using generative AI","volume":"21","author":"H Cui","year":"2024","journal-title":"Nat Methods"},{"issue":"9","key":"pcbi.1014806.ref047","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/ni.3795","article-title":"Translation is actively regulated during the differentiation of CD8+ effector T cells","volume":"18","author":"K Araki","year":"2017","journal-title":"Nat Immunol"},{"issue":"8","key":"pcbi.1014806.ref048","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/s41590-020-0714-5","article-title":"Dynamics in protein translation sustaining T cell preparedness","volume":"21","author":"T Wolf","year":"2020","journal-title":"Nat Immunol"},{"issue":"3","key":"pcbi.1014806.ref049","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41423-021-00792-8","article-title":"Protein synthesis, degradation, and energy metabolism in T cell immunity","volume":"19","author":"JM Marchingo","year":"2022","journal-title":"Cell Mol Immunol"},{"issue":"4","key":"pcbi.1014806.ref050","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1093\/nar\/gkw010","article-title":"Mechanism and regulation of the nonsense-mediated decay pathway","volume":"44","author":"N Hug","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pcbi.1014806.ref051","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.it.2021.03.008","article-title":"RNA decay machinery safeguards immune cell development and immunological responses","volume":"42","author":"T Akiyama","year":"2021","journal-title":"Trends Immunol"},{"issue":"4","key":"pcbi.1014806.ref052","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/his.13250","article-title":"Alterted SLIT2\/ROBO1 signalling is linked to impaired placentation of missed and threatened miscarriage in early pregnancy","volume":"71","author":"P Li","year":"2017","journal-title":"Histopathology"},{"key":"pcbi.1014806.ref053","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.placenta.2024.06.005","article-title":"Comparative proteomics analysis of decidua reveals altered RNA processing and impaired ribosome function in recurrent pregnancy loss","volume":"154","author":"K Davalieva","year":"2024","journal-title":"Placenta"},{"issue":"5","key":"pcbi.1014806.ref054","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1172\/JCI87490","article-title":"Risks associated with viral infections during pregnancy","volume":"127","author":"K Racicot","year":"2017","journal-title":"J Clin Invest"},{"issue":"8","key":"pcbi.1014806.ref055","doi-asserted-by":"crossref","first-page":"983","DOI":"10.3109\/14767058.2010.547963","article-title":"Role of the infections in recurrent spontaneous abortion","volume":"24","author":"G Nigro","year":"2011","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"1","key":"pcbi.1014806.ref056","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1038\/s41467-019-10015-4","article-title":"Competition for nutrients and its role in controlling immune responses","volume":"10","author":"N Kedia-Mehta","year":"2019","journal-title":"Nat Commun"},{"issue":"1","key":"pcbi.1014806.ref057","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/s41467-023-36637-3","article-title":"ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs","volume":"14","author":"B He","year":"2023","journal-title":"Nat Commun"},{"issue":"2","key":"pcbi.1014806.ref058","first-page":"240","article-title":"The clinical use of corticosteroids in pregnancy","volume":"22","author":"MW Kemp","year":"2016","journal-title":"Hum Reprod Update"},{"issue":"1","key":"pcbi.1014806.ref059","first-page":"89","article-title":"Effect of Prednisolone Administration on Patients with Unexplained Recurrent Miscarriage and in Routine Intracytoplasmic Sperm Injection: A Meta-Analysis. Am J Reprod Immunol N Y N 1989","volume":"74","author":"S Dan","year":"2015"},{"issue":"1","key":"pcbi.1014806.ref060","article-title":"Efficacy of Corticosteroids in Patients With Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis. Am J Reprod Immunol N Y N 1989","volume":"93","author":"S D\u2019Ippolito","year":"2025"},{"issue":"12","key":"pcbi.1014806.ref061","first-page":"1545","article-title":"Rapamycin Corrects T Regulatory Cell Depletion and Improves Embryo Implantation and Live Birth Rates in a Murine Model. Reprod Sci Thousand Oaks Calif","volume":"26","author":"GD Royster","year":"2019"},{"issue":"9","key":"pcbi.1014806.ref062","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1080\/15548627.2020.1833515","article-title":"Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence","volume":"17","author":"H Lu","year":"2021","journal-title":"Autophagy"},{"key":"pcbi.1014806.ref063","doi-asserted-by":"crossref","first-page":"105730","DOI":"10.1016\/j.intimp.2019.105730","article-title":"Sirolimus as a new drug to treat RIF patients with elevated Th17\/Treg ratio: A double-blind, phase II randomized clinical trial","volume":"74","author":"M Ahmadi","year":"2019","journal-title":"Int Immunopharmacol"},{"issue":"8","key":"pcbi.1014806.ref064","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.4049\/jimmunol.1502482","article-title":"Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species-Induced Mouse Model","volume":"197","author":"F Morin","year":"2016","journal-title":"J Immunol"},{"issue":"1","key":"pcbi.1014806.ref065","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12967-021-02760-2","article-title":"Niclosamide suppresses the expansion of follicular helper T cells and alleviates disease severity in two murine models of lupus via STAT3","volume":"19","author":"SG Jang","year":"2021","journal-title":"J Transl Med"},{"issue":"1","key":"pcbi.1014806.ref066","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1186\/s12885-019-5828-5","article-title":"Verification of the effects of calcium channel blockers on the immune microenvironment of breast cancer","volume":"19","author":"K Takada","year":"2019","journal-title":"BMC Cancer"},{"issue":"7","key":"pcbi.1014806.ref067","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.3390\/pharmaceutics14071478","article-title":"The Ca2+ Channel Blocker Verapamil Inhibits the In Vitro Activation and Function of T Lymphocytes: A 2022 Reappraisal","volume":"14","author":"JI Veytia-Bucheli","year":"2022","journal-title":"Pharmaceutics"},{"issue":"2","key":"pcbi.1014806.ref068","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrg1272","article-title":"Network biology: understanding the cell\u2019s functional organization","volume":"5","author":"A-L Barab\u00e1si","year":"2004","journal-title":"Nat Rev Genet"},{"issue":"1","key":"pcbi.1014806.ref069","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12918-018-0598-2","article-title":"A systematic survey of centrality measures for protein-protein interaction networks","volume":"12","author":"M Ashtiani","year":"2018","journal-title":"BMC Syst Biol"},{"key":"pcbi.1014806.ref070","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.imlet.2016.06.006","article-title":"CXCR4 signaling in health and disease","volume":"177","author":"T Pozzobon","year":"2016","journal-title":"Immunol Lett"},{"issue":"3","key":"pcbi.1014806.ref071","doi-asserted-by":"crossref","DOI":"10.1002\/jgm.3467","article-title":"Maternal ApoE genotype and risk of recurrent pregnancy loss: An updated systematic review and meta-analysis","volume":"25","author":"S Cargnin","year":"2023","journal-title":"J Gene Med"},{"issue":"2","key":"pcbi.1014806.ref072","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/14647273.2018.1524935","article-title":"Prevalence of candidate single nucleotide polymorphisms on p53, IL-11, IL-10, VEGF and APOE in patients with repeated implantation failure (RIF) and pregnancy loss (RPL)","volume":"23","author":"A Turienzo","year":"2020","journal-title":"Hum Fertil (Camb)"},{"issue":"7421","key":"pcbi.1014806.ref073","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nature11530","article-title":"BATF-JUN is critical for IRF4-mediated transcription in T cells","volume":"490","author":"P Li","year":"2012","journal-title":"Nature"},{"issue":"7786","key":"pcbi.1014806.ref074","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41586-019-1805-z","article-title":"c-Jun overexpression in CAR T cells induces exhaustion resistance","volume":"576","author":"RC Lynn","year":"2019","journal-title":"Nature"},{"issue":"12","key":"pcbi.1014806.ref075","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1038\/nm962","article-title":"Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo","volume":"9","author":"DG Millar","year":"2003","journal-title":"Nat Med"},{"issue":"2","key":"pcbi.1014806.ref076","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.immuni.2004.07.005","article-title":"Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk","volume":"21","author":"J Colgan","year":"2004","journal-title":"Immunity"},{"key":"pcbi.1014806.ref077","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2147\/JAA.S308938","article-title":"Cyclophilin A Plays Potential Roles in a Rat Model of Asthma and Suppression of Immune Response","volume":"14","author":"C-T Chen","year":"2021","journal-title":"J Asthma Allergy"},{"issue":"9","key":"pcbi.1014806.ref078","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.autrev.2018.04.004","article-title":"Vimentin as antigenic target in autoimmunity: A comprehensive review","volume":"17","author":"A Musaelyan","year":"2018","journal-title":"Autoimmun Rev"},{"issue":"10","key":"pcbi.1014806.ref079","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1172\/JCI95713","article-title":"The vimentin intermediate filament network restrains regulatory T cell suppression of graft-versus-host disease","volume":"128","author":"C McDonald-Hyman","year":"2018","journal-title":"J Clin Invest"},{"key":"pcbi.1014806.ref080","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.imlet.2019.11.007","article-title":"CXCL12\/CXCR4 signal transduction in diseases and its molecular approaches in targeted-therapy","volume":"217","author":"A Mousavi","year":"2020","journal-title":"Immunol Lett"},{"issue":"21","key":"pcbi.1014806.ref081","article-title":"Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation","volume":"8","author":"F Lyu","year":"2023","journal-title":"JCI Insight"},{"issue":"10","key":"pcbi.1014806.ref082","article-title":"Decidual CXCR4+CD56brightNK cells as a novel NK subset in maternal\u2013foetal immune tolerance to alleviate early pregnancy failure","volume":"11","author":"Y Tao","year":"2021","journal-title":"Clin Transl Med"},{"issue":"12","key":"pcbi.1014806.ref083","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0188882","article-title":"CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis","volume":"12","author":"KM Ramonell","year":"2017","journal-title":"PLoS One"},{"issue":"4","key":"pcbi.1014806.ref084","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s00262-022-03298-y","article-title":"Comprehensive analysis of the immunological implication and prognostic value of CXCR4 in non-small cell lung cancer","volume":"72","author":"W Guo","year":"2023","journal-title":"Cancer Immunol Immunother"},{"issue":"20","key":"pcbi.1014806.ref085","doi-asserted-by":"crossref","first-page":"9959","DOI":"10.1073\/pnas.1820604116","article-title":"Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor","volume":"116","author":"GP Mognol","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pcbi.1014806.ref086","doi-asserted-by":"crossref","DOI":"10.1038\/ncb0502-e131","article-title":"AP-1 as a regulator of cell life and death","volume":"4","author":"E Shaulian","year":"2002","journal-title":"Nat Cell Biol"},{"issue":"1","key":"pcbi.1014806.ref087","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20182009","article-title":"AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation","volume":"217","author":"M Yukawa","year":"2019","journal-title":"J Exp Med"},{"issue":"11","key":"pcbi.1014806.ref088","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.4049\/jimmunol.161.11.6084","article-title":"Regulation of NF-\u03baB, AP-1, NFAT, and STAT1 Nuclear Import in T Lymphocytes by Noninvasive Delivery of Peptide Carrying the Nuclear Localization Sequence of NF-\u03baB p501","volume":"161","author":"TR Torgerson","year":"1998","journal-title":"J Immunol"},{"issue":"6","key":"pcbi.1014806.ref089","first-page":"2269","article-title":"AP-1 Transcription Factors c-FOS and c-JUN Mediate GnRH-Induced Cadherin-11 Expression and Trophoblast Cell Invasion. Endocrinology","author":"B Peng","year":"2015"},{"issue":"1","key":"pcbi.1014806.ref090","doi-asserted-by":"crossref","first-page":"6155","DOI":"10.1038\/s41467-024-50485-9","article-title":"C-JUN overexpressing CAR-T cells in acute myeloid leukemia: preclinical characterization and phase I trial","volume":"15","author":"S Zuo","year":"2024","journal-title":"Nat Commun"},{"key":"pcbi.1014806.ref091","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.3389\/fimmu.2019.02317","article-title":"Dynamic Function and Composition Changes of Immune Cells During Normal and Pathological Pregnancy at the Maternal-Fetal Interface","volume":"10","author":"F Yang","year":"2019","journal-title":"Front Immunol"},{"issue":"12","key":"pcbi.1014806.ref092","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giaa151","article-title":"SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data","volume":"9","author":"MD Young","year":"2020","journal-title":"GigaScience"},{"issue":"4","key":"pcbi.1014806.ref093","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","author":"SL Wolock","year":"2019","journal-title":"Cell Syst"},{"issue":"12","key":"pcbi.1014806.ref094","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"I Korsunsky","year":"2019","journal-title":"Nat Methods"},{"issue":"3","key":"pcbi.1014806.ref095","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1093\/bioinformatics\/btz625","article-title":"BBKNN: fast batch alignment of single cell transcriptomes","volume":"36","author":"K Pola\u0144ski","year":"2020","journal-title":"Bioinformatics"},{"issue":"6594","key":"pcbi.1014806.ref096","doi-asserted-by":"crossref","DOI":"10.1126\/science.abl5197","article-title":"Cross-tissue immune cell analysis reveals tissue-specific features in humans","volume":"376","author":"C Dom\u00ednguez Conde","year":"2022","journal-title":"Science"},{"issue":"6","key":"pcbi.1014806.ref097","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1101\/gr.262774.120","article-title":"Single-cell analysis of human embryos reveals diverse patterns of aneuploidy and mosaicism","volume":"30","author":"MR Starostik","year":"2020","journal-title":"Genome Res"},{"issue":"1","key":"pcbi.1014806.ref098","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1186\/s12864-017-4253-x","article-title":"Mosaic autosomal aneuploidies are detectable from single-cell RNAseq data","volume":"18","author":"JA Griffiths","year":"2017","journal-title":"BMC Genomics"},{"issue":"16","key":"pcbi.1014806.ref099","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"1110","key":"pcbi.1014806.ref100","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"GA Van der Auwera","year":"2013","journal-title":"Curr Protoc Bioinformatics"},{"issue":"12","key":"pcbi.1014806.ref101","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"pcbi.1014806.ref102","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: the DrugBank Knowledgebase for 2024","volume":"52","author":"C Knox","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1014806.ref103","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"D Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1014806.ref104","doi-asserted-by":"crossref","unstructured":"Hagberg AA, Schult DA, Swart PJ. Exploring Network Structure, Dynamics, and Function using Network. In: Proceedings of the Python in Science Conference [Internet]. Pasadena, California: SciPy; 2008 [cited 2025 Jul 24]. p. 11\u20135. 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