DRPPM-PATH-SURVEIOR: Plug-and-Play Survival Analysis of Pathway-level Signatures and Immune Components.

Autor:	Obermayer A; H. Lee Moffitt Cancer Center and Research Institute., Chang D; H. Lee Moffitt Cancer Center and Research Institute., Nobles G; H. Lee Moffitt Cancer Center and Research Institute., Teng M; H. Lee Moffitt Cancer Center and Research Institute., Tan AC; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT., Wang X; H. Lee Moffitt Cancer Center and Research Institute., Eschrich S; H. Lee Moffitt Cancer Center and Research Institute., Rodriguez P; H. Lee Moffitt Cancer Center and Research Institute., Grass GD; H. Lee Moffitt Cancer Center and Research Institute., Meshinchi S; Fred Hutchinson Cancer Research Center, Seattle, WA., Tarhini A; H. Lee Moffitt Cancer Center and Research Institute., Chen DT; H. Lee Moffitt Cancer Center and Research Institute., Shaw T; H. Lee Moffitt Cancer Center and Research Institute.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Mar 14. Date of Electronic Publication: 2023 Mar 14.
DOI:	10.21203/rs.3.rs-2688545/v1
Abstrakt:	Pathway-level survival analysis offers the opportunity to examine molecular pathways and immune signatures that influence patient outcomes. However, available survival analysis algorithms are limited in pathway-level function and lack a streamlined analytical process. Here we present a comprehensive pathway-level survival analysis suite, DRPPM-PATH-SURVEIOR, which includes a Shiny user interface with extensive features for systematic exploration of pathways and covariates in a Cox proportional-hazard model. Moreover, our framework offers an integrative strategy for performing Hazard Ratio ranked Gene Set Enrichment Analysis (GSEA) and pathway clustering. As an example, we applied our tool in a combined cohort of melanoma patients treated with checkpoint inhibition (ICI) and identified several immune populations and biomarkers predictive of ICI efficacy. We also analyzed gene expression data of pediatric acute myeloid leukemia (AML) and performed an inverse association of drug targets with the patient's clinical endpoint. Our analysis derived several drug targets in high-risk KMT2A-fusion-positive patients, which were then validated in AML cell lines in the Genomics of Drug Sensitivity database. Altogether, the tool offers a comprehensive suite for pathway-level survival analysis and a user interface for exploring drug targets, molecular features, and immune populations at different resolutions. Competing Interests: Competing interests: TIS, AO, and DTC report a provisional patent application for the DRPPM-PATH-SURVEIOR software. SAE reports intellectual property (RSI) and stock in Cvergenx. AT reports grants from Bristol Myers Squib, grants from Genentech-Roche, grants from Regeneron, grants from Sanofi-Genzyme, grants from Nektar, grants from Clinigen, grants from Merck, grants from Acrotech, grants from Pfizer, grants from Checkmate, grants from OncoSec, personal fees from Bristol Myers Squibb, personal fees from Merck, personal fees from Easai, personal fees from Instil Bio, personal fees from Clinigin, personal fees from Regeneron, personal fees from Sanofi-Genzyme, personal fees from Novartis, personal fees from Partner Therapeutics, personal fees from Genentech/Roche, personal fees from BioNTech, outside the submitted work. DC, GN, MT, ACT, GDG, XW, PR, and SM declare no other conflict of interest.
Databáze:	MEDLINE
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