A multimodal precision oncology platform integrating genomics,single-cell transcriptomics, and functional drug screening expandstherapeutic options in pediatric brain tumors
- 1University of Utah
Abstract
Precision oncology for pediatric brain tumors mainly relies on clinically validated, targetable genomic alterations, which are often sparse, yield few matched therapies, and do not guide chemotherapy selection. We developed a tiered framework in which deep whole-genome sequencing and single-cell RNA sequencing extend targeted-therapy selection, with ex vivo functional drug screening supporting selection of both targeted therapies and chemotherapies. We applied it to 17 children with malignant CNS tumors. The approach expanded recommendations beyond genomics: functional screening provided every patient with at least one high-confidence targeted-therapy or chemotherapy nomination, while single-cell RNA sequencing identified an average of 37 druggable gene targets per patient, producing a fourfold increase in high-confidence targeted-therapy recommendations. In an exploratory analysis, functional classifications were directionally consistent with outcomes in 8 of 10 evaluable cases, although combination treatments and radiation precluded causal attribution. Single-cell profiling also identified subclone-specific vulnerabilities, supporting prospective evaluation of the platform's feasibility and predictive utility.
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BibTeX
@misc{huang2026multimodal,
title = {{A multimodal precision oncology platform integrating genomics,single-cell transcriptomics, and functional drug screening expandstherapeutic options in pediatric brain tumors}},
author = {X. Huang and Y. Qiao and G. S. Black and C. R. Sederman and H. Yang and T. Musci and A. Ludwick and G. He and O. Youssef and M. Gutierrez and J. Yang and P. P. Chan and T. H. Memmott and N. S. Whipple and C. S. Bruggers and A. Quinlan and P. J. Moos and S. H. Cheshier and G. T. Marth},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.12.758619},
url = {https://www.biorxiv.org/content/10.64898/2026.10.12.758619v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A multimodal precision oncology platform integrating genomics,single-cell transcriptomics, and functional drug screening expandstherapeutic options in pediatric brain tumors
AU - X. Huang
AU - Y. Qiao
AU - G. S. Black
AU - C. R. Sederman
AU - H. Yang
AU - T. Musci
AU - A. Ludwick
AU - G. He
AU - O. Youssef
AU - M. Gutierrez
AU - J. Yang
AU - P. P. Chan
AU - T. H. Memmott
AU - N. S. Whipple
AU - C. S. Bruggers
AU - A. Quinlan
AU - P. J. Moos
AU - S. H. Cheshier
AU - G. T. Marth
PY - 2026
DA - 2026/10/12
PB - bioRxiv
DO - 10.64898/2026.10.12.758619
UR - https://www.biorxiv.org/content/10.64898/2026.10.12.758619v1
AB - Precision oncology for pediatric brain tumors mainly relies on clinically validated, targetable genomic alterations, which are often sparse, yield few matched therapies, and do not guide chemotherapy selection. We developed a tiered framework in which deep whole-genome sequencing and single-cell RNA sequencing extend targeted-therapy selection, with ex vivo functional drug screening supporting selection of both targeted therapies and chemotherapies. We applied it to 17 children with malignant CNS tumors. The approach expanded recommendations beyond genomics: functional screening provided every patient with at least one high-confidence targeted-therapy or chemotherapy nomination, while single-cell RNA sequencing identified an average of 37 druggable gene targets per patient, producing a fourfold increase in high-confidence targeted-therapy recommendations. In an exploratory analysis, functional classifications were directionally consistent with outcomes in 8 of 10 evaluable cases, although combination treatments and radiation precluded causal attribution. Single-cell profiling also identified subclone-specific vulnerabilities, supporting prospective evaluation of the platform's feasibility and predictive utility.
ER -