Quantitative Evaluation of Colorectal Cancer Organoid Genomic and Transcriptomic Fidelity Using a Dual-Reference Divergence Framework

Author : Eli Reuveni, Ram Oren

Abstract : Patient-derived colorectal cancer (CRC) organoids are cornerstone models in translational oncology, yet distinguishing true tumor-specific evolution from in vitro culture artifacts across multi-omics profiles remains a critical methodological hurdle. Here, we establish a robust computational framework to systematically quantify copy number variation (CNV), gene expression divergence, and clonal heterogeneity across CRC patient cohorts. By integrating multi-metric genomic and transcriptomic profiles encompassing entropy, amplitude, directional alterations, and expression shifts against dual reference baselines, we uncover significant patient-specific divergence. Furthermore, our profiling identifies evolutionary hotspots of organoid selection, highlighting regions prone to in vitro adaptation in CRC models. Patient-specific composite aberration scoring successfully categorizes cohort heterogeneity and identifies high-divergence tumor models. This methodology provides researchers with an unbiased guideline for assessing organoid fidelity, uncovering evolutionary selection pressures, and enhancing the translational reliability of precision colorectal cancer models.

Keywords : Colorectal Cancer, Patient-Derived Organoids, Genomic Fidelity, Evolutionary Selection, Clonal Heterogeneity

Conference Name : International Conference on Biomedical Genomics and Bioinformatics (ICBGB - 26)

Conference Place : Vienna, Austria

Conference Date : 6th Oct 2026