{"doi":"10.1101/2020.09.11.290353","title":"Integration of Biodynamic Imaging and RNA-seq classifies chemotherapy response in canine diffuse large B-cell lymphoma","abstract":"Abstract Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive cancer of notorious genotypic and phenotypic heterogeneity. A major challenge is predicting response to drug treatment, which has typically been done using genomic tools alone with little success. A novel method that incorporates phenotypic profiling for predicting the effectiveness of therapy for individual patients is desperately needed. BioDynamic Imaging (BDI) is a technique for measuring time-dependent fluctuations in back-scattered light through living tumor tissues to identify critical changes in intracellular dynamics that are associated with phenotypic response to drugs. In this study, BDI and RNA sequencing (RNA-seq) data were collected on tumor samples from dogs with naturally occurring DLBCL, an animal model of increasingly recognized relevance to the human disease. BDI and RNA-seq data were combined to identify correlations between gene co-expression modules and linear combinations of biomarkers to provide biological mechanistic interpretations of BDI biomarkers. Using regularized multivariate logistic regression, we combined RNA-seq and BDI data to develop a novel model to accurately classify the clinical response of canine DLBCL to combination chemotherapy (i.e. CHOP). Our model incorporates data on the expression of 4 genes and 3 BDI-derived phenotypic biomarkers, capturing changes in transcription, microtubule related processes, and apoptosis. This pilot study suggests that the combination of multi-scale transcriptomic and phenotypic data can identify patients that respond to a given treatment a priori in a disease that has been difficult to treat. Our work provides an important framework for future development of strategies and treatments in precision cancer medicine.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130989,"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":0.9465,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":303986,"name":"Sagar M. Utturkar","orcid":"0000-0002-3453-1948","position":1,"is_corresponding":false},{"id":317336,"name":"Deepika Dhawan","orcid":"0000-0002-5456-9302","position":2,"is_corresponding":false},{"id":584944,"name":"Phillip San Miguel","orcid":null,"position":3,"is_corresponding":false},{"id":345364,"name":"Gaurav Chopra","orcid":"0000-0003-0942-7898","position":4,"is_corresponding":false},{"id":378928,"name":"John Turek","orcid":"0000-0003-4631-7356","position":5,"is_corresponding":false},{"id":378929,"name":"David D. Nolte","orcid":"0000-0002-4872-9357","position":6,"is_corresponding":false},{"id":584288,"name":"Michael O. Childress","orcid":"0000-0001-6127-4679","position":7,"is_corresponding":false},{"id":338751,"name":"Nadia A. Lanman","orcid":"0000-0002-1819-7070","position":8,"is_corresponding":false},{"id":295508,"name":"Jonathan Fine","orcid":"0000-0002-3685-8581","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:16:00.235845Z","pmid":null,"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":[]}