{"doi":"10.1101/2023.04.25.538191","title":"Generating immunogenomic data-guided virtual patients using a QSP model to predict response of advanced NSCLC to PD-L1 inhibition","abstract":"Generating realistic virtual patients from a limited amount of patient data is one of the major challenges for quantitative systems pharmacology modeling in immuno-oncology. Quantitative systems pharmacology (QSP) is a mathematical modeling methodology that integrates mechanistic knowledge of biological systems to investigate dynamics in a whole system during disease progression and drug treatment. In the present analysis, we parameterized our previously published QSP model of the cancer-immunity cycle to non-small cell lung cancer (NSCLC) and generated a virtual patient cohort to predict clinical response to PD-L1 inhibition in NSCLC. The virtual patient generation was guided by immunogenomic data from iAtlas portal and population pharmacokinetic data of durvalumab, a PD-L1 inhibitor. With virtual patients generated following the immunogenomic data distribution, our model predicted a response rate of 18.6% (95% bootstrap confidence interval: 13.3-24.2%) and identified CD8/Treg ratio as a potential predictive biomarker in addition to PD-L1 expression and tumor mutational burden. We demonstrated that omics data served as a reliable resource for virtual patient generation techniques in immuno-oncology using QSP models.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":406761,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9388,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1035009,"name":"Theinmozhi Arulraj","orcid":"0000-0002-7258-7512","position":1,"is_corresponding":false},{"id":686648,"name":"Holly Kimko","orcid":"0000-0003-1456-4862","position":2,"is_corresponding":false},{"id":299224,"name":"Aleksander S. Popel","orcid":"0000-0002-6706-9235","position":3,"is_corresponding":false},{"id":323175,"name":"Hanwen Wang","orcid":"0000-0001-5480-431X","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T01:21:03.432924Z","pmid":"37162938","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}