{"id":"https://openalex.org/W7077889841","doi":"https://doi.org/10.48550/arxiv.2508.18638","title":"Biologically Disentangled Multi-Omic Modeling Reveals Mechanistic Insights into Pan-Cancer Immunotherapy Resistance","display_name":"Biologically Disentangled Multi-Omic Modeling Reveals Mechanistic Insights into Pan-Cancer Immunotherapy Resistance","publication_year":2025,"publication_date":"2025-08-26","ids":{"openalex":"https://openalex.org/W7077889841","doi":"https://doi.org/10.48550/arxiv.2508.18638"},"language":"en","primary_location":{"id":"doi:10.48550/arxiv.2508.18638","is_oa":true,"landing_page_url":"https://doi.org/10.48550/arxiv.2508.18638","pdf_url":null,"source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I205783295","host_organization_name":"Cornell University","host_organization_lineage":["https://openalex.org/I205783295"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"article"},"type":"preprint","indexed_in":["datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.48550/arxiv.2508.18638","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Tariq, Ifrah","orcid":null},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Tariq, Ifrah","raw_affiliation_strings":[],"affiliations":[]},{"author_position":"last","author":{"id":null,"display_name":"Fraenkel, Ernest","orcid":null},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Fraenkel, Ernest","raw_affiliation_strings":[],"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":true,"primary_topic":{"id":"https://openalex.org/T12157","display_name":"Geochemistry and Geologic Mapping","score":0.6491000056266785,"subfield":{"id":"https://openalex.org/subfields/1702","display_name":"Artificial Intelligence"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T12157","display_name":"Geochemistry and Geologic Mapping","score":0.6491000056266785,"subfield":{"id":"https://openalex.org/subfields/1702","display_name":"Artificial Intelligence"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T13067","display_name":"Geological Modeling and Analysis","score":0.024800000712275505,"subfield":{"id":"https://openalex.org/subfields/1906","display_name":"Geochemistry and Petrology"},"field":{"id":"https://openalex.org/fields/19","display_name":"Earth and Planetary Sciences"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T14311","display_name":"Electrical and Electromagnetic Research","score":0.019600000232458115,"subfield":{"id":"https://openalex.org/subfields/3107","display_name":"Atomic and Molecular Physics, and Optics"},"field":{"id":"https://openalex.org/fields/31","display_name":"Physics and Astronomy"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/interpretability","display_name":"Interpretability","score":0.8776000142097473},{"id":"https://openalex.org/keywords/autoencoder","display_name":"Autoencoder","score":0.5641999840736389},{"id":"https://openalex.org/keywords/inference","display_name":"Inference","score":0.46709999442100525},{"id":"https://openalex.org/keywords/immunotherapy","display_name":"Immunotherapy","score":0.42149999737739563},{"id":"https://openalex.org/keywords/biological-data","display_name":"Biological data","score":0.3440999984741211},{"id":"https://openalex.org/keywords/biological-network","display_name":"Biological network","score":0.3431999981403351},{"id":"https://openalex.org/keywords/modular-design","display_name":"Modular design","score":0.33869999647140503},{"id":"https://openalex.org/keywords/immune-system","display_name":"Immune system","score":0.33219999074935913},{"id":"https://openalex.org/keywords/mechanism","display_name":"Mechanism (biology)","score":0.3303999900817871}],"concepts":[{"id":"https://openalex.org/C2781067378","wikidata":"https://www.wikidata.org/wiki/Q17027399","display_name":"Interpretability","level":2,"score":0.8776000142097473},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.5672000050544739},{"id":"https://openalex.org/C101738243","wikidata":"https://www.wikidata.org/wiki/Q786435","display_name":"Autoencoder","level":3,"score":0.5641999840736389},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5232999920845032},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.48249998688697815},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.47920000553131104},{"id":"https://openalex.org/C2776214188","wikidata":"https://www.wikidata.org/wiki/Q408386","display_name":"Inference","level":2,"score":0.46709999442100525},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.42149999737739563},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.36250001192092896},{"id":"https://openalex.org/C201797286","wikidata":"https://www.wikidata.org/wiki/Q4914986","display_name":"Biological data","level":2,"score":0.3440999984741211},{"id":"https://openalex.org/C28225019","wikidata":"https://www.wikidata.org/wiki/Q4915005","display_name":"Biological network","level":2,"score":0.3431999981403351},{"id":"https://openalex.org/C101468663","wikidata":"https://www.wikidata.org/wiki/Q1620158","display_name":"Modular design","level":2,"score":0.33869999647140503},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.33219999074935913},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.3303999900817871},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.32910001277923584},{"id":"https://openalex.org/C153083717","wikidata":"https://www.wikidata.org/wiki/Q6535263","display_name":"Leverage (statistics)","level":2,"score":0.32170000672340393},{"id":"https://openalex.org/C108583219","wikidata":"https://www.wikidata.org/wiki/Q197536","display_name":"Deep learning","level":2,"score":0.3172999918460846},{"id":"https://openalex.org/C163763905","wikidata":"https://www.wikidata.org/wiki/Q17075943","display_name":"Precision medicine","level":2,"score":0.3142000138759613},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3010999858379364},{"id":"https://openalex.org/C98108389","wikidata":"https://www.wikidata.org/wiki/Q412563","display_name":"CRISPR","level":3,"score":0.2953000068664551},{"id":"https://openalex.org/C9927688","wikidata":"https://www.wikidata.org/wiki/Q4915012","display_name":"Biological pathway","level":4,"score":0.2818000018596649},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.27250000834465027},{"id":"https://openalex.org/C145741570","wikidata":"https://www.wikidata.org/wiki/Q7251534","display_name":"Proteogenomics","level":5,"score":0.26570001244544983},{"id":"https://openalex.org/C2780851360","wikidata":"https://www.wikidata.org/wiki/Q21686041","display_name":"Immune checkpoint","level":4,"score":0.2644999921321869},{"id":"https://openalex.org/C2776291640","wikidata":"https://www.wikidata.org/wiki/Q2912517","display_name":"Value (mathematics)","level":2,"score":0.26409998536109924},{"id":"https://openalex.org/C114851261","wikidata":"https://www.wikidata.org/wiki/Q12147416","display_name":"Drug resistance","level":2,"score":0.26080000400543213},{"id":"https://openalex.org/C167966045","wikidata":"https://www.wikidata.org/wiki/Q5532625","display_name":"Generative model","level":3,"score":0.2565000057220459},{"id":"https://openalex.org/C152662350","wikidata":"https://www.wikidata.org/wiki/Q815297","display_name":"Systems biology","level":2,"score":0.2549999952316284},{"id":"https://openalex.org/C189206191","wikidata":"https://www.wikidata.org/wiki/Q222046","display_name":"Genomics","level":4,"score":0.25040000677108765}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.48550/arxiv.2508.18638","is_oa":true,"landing_page_url":"https://doi.org/10.48550/arxiv.2508.18638","pdf_url":null,"source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I205783295","host_organization_name":"Cornell University","host_organization_lineage":["https://openalex.org/I205783295"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":null,"raw_source_name":null,"raw_type":"article"}],"best_oa_location":{"id":"doi:10.48550/arxiv.2508.18638","is_oa":true,"landing_page_url":"https://doi.org/10.48550/arxiv.2508.18638","pdf_url":null,"source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I205783295","host_organization_name":"Cornell University","host_organization_lineage":["https://openalex.org/I205783295"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"article"},"sustainable_development_goals":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Immune":[0],"checkpoint":[1],"inhibitors":[2],"(ICIs)":[3],"have":[4],"transformed":[5],"cancer":[6,113],"treatment,":[7],"yet":[8],"patient":[9],"responses":[10,31],"remain":[11],"highly":[12],"variable,":[13],"and":[14,39,67,72,100,130,140,170,198],"the":[15,44,54,186],"biological":[16,45,151],"mechanisms":[17],"underlying":[18],"resistance":[19,133,147,196],"are":[20],"poorly":[21],"understood.":[22],"While":[23],"machine":[24,191],"learning":[25,192],"models":[26],"hold":[27],"promise":[28],"for":[29],"predicting":[30],"to":[32,48,90,104,177],"ICIs,":[33,117],"most":[34],"existing":[35,76],"methods":[36],"lack":[37],"interpretability":[38],"do":[40],"not":[41],"effectively":[42],"leverage":[43],"structure":[46],"inherent":[47],"multi-omics":[49],"data.":[50],"Here,":[51],"we":[52],"introduce":[53],"Biologically":[55],"Disentangled":[56],"Variational":[57],"Autoencoder":[58],"(BDVAE),":[59],"a":[60,82,105,149],"deep":[61],"generative":[62],"model":[63],"that":[64,146],"integrates":[65],"transcriptomic":[66],"genomic":[68],"data":[69],"through":[70],"modality-":[71],"pathway-specific":[73],"encoders.":[74],"Unlike":[75],"rigid,":[77],"pathway-informed":[78],"models,":[79],"BDVAE":[80,118,144],"employs":[81],"modular":[83],"encoder":[84],"architecture":[85],"combined":[86],"with":[87,97,116,167],"variational":[88],"inference":[89],"learn":[91],"biologically":[92,189],"meaningful":[93],"latent":[94,164],"features":[95,165],"associated":[96],"immune,":[98],"genomic,":[99],"metabolic":[101,138],"processes.":[102],"Applied":[103],"pan-cancer":[106],"cohort":[107],"of":[108,160,188],"366":[109],"patients":[110],"across":[111],"four":[112],"types":[114],"treated":[115],"accurately":[119],"predicts":[120],"treatment":[121],"response":[122],"(AUC-ROC":[123],"=":[124],"0.94":[125],"on":[126],"unseen":[127],"test":[128],"data)":[129],"uncovers":[131],"critical":[132],"mechanisms,":[134],"including":[135],"immune":[136],"suppression,":[137],"shifts,":[139],"neuronal":[141],"signaling.":[142],"Importantly,":[143],"reveals":[145],"spans":[148],"continuous":[150],"spectrum":[152],"rather":[153],"than":[154],"strictly":[155],"binary":[156],"states,":[157],"reflecting":[158],"gradations":[159],"tumor":[161],"dysfunction.":[162],"Several":[163],"correlate":[166],"survival":[168],"outcomes":[169],"known":[171],"clinical":[172],"subtypes,":[173],"demonstrating":[174],"BDVAE's":[175],"capability":[176],"generate":[178],"interpretable,":[179],"clinically":[180],"relevant":[181],"insights.":[182],"These":[183],"findings":[184],"underscore":[185],"value":[187],"structured":[190],"in":[193],"elucidating":[194],"complex":[195],"patterns":[197],"guiding":[199],"precision":[200],"immunotherapy":[201],"strategies.":[202]},"counts_by_year":[],"updated_date":"2025-11-06T06:51:31.235846","created_date":"2025-10-10T00:00:00"}
