Biology subjects

Pichotta, K.

Publications and source records attributed to Pichotta, K..

2 recordsLinked to original sources

bioRxiv2026

A Pan-Cancer Ex Vivo Drug Screen Atlas for Functional Precision Oncology

Compared to immortalized cell lines, patient-derived organoids and other ex vivo models have been shown to better recapitulate patient responses to therapy. High cost and technical complexity have prevented the creation of pan-cancer ex vivo datasets, limiting comprehensive analyses and predictive modeling for ex vivo drug response. We present the Pan-PreClinical (PPC) project: a drug screen atlas of 2.1M experiments across 1,982 ex vivo samples and 3,100 drugs spanning 134 cancer indications tested across 26 studies. We develop a contrastive Bayesian model to harmonize across studies, identifying 303 tissue-specific drug sensitivities and demonstrating drug sensitivities are predictive of clinically-relevant molecular profiles. Integrating established cell line databases reveals systematic biases across 55 cancer subtypes, with cell line screens favoring drugs targeting highly proliferative cells and undervaluing cell-cell communication targets. We leverage PPC to establish an ex vivo foundation model and computational platform for scalable ex vivo cancer biology and predictive oncology.

cancer biology↗

bioRxiv2024

Machine learning predictions improve identification of real-world cancer driver mutations

Characterizing and validating which mutations influence development of cancer is challenging. Machine learning has delivered significant advances in protein structure prediction, but its utility for identifying cancer drivers is less explored. We evaluated multiple computational methods for identifying cancer driver alterations. For identifying known drivers, methods incorporating protein structure or functional genomic data outperformed methods trained only on evolutionary data. We further validated VUSs annotated as pathogenic by testing their association with overall survival in two cohorts of patients with non-small cell lung cancer (N=7,965 and 977). "Pathogenic" VUSs in KEAP1 and SMARCA4 identified by several methods were associated with worse survival, unlike "benign" VUSs. "Pathogenic" VUSs exhibited mutual exclusivity with known oncogenic alterations at the pathway level, further suggesting biological validity. Despite training primarily on germline, rather than somatic, mutation data, computational predictions contribute to a more comprehensive understanding of tumor genetics as validated by real-world data.

genomics↗