Search bioRxiv⌕ Search

Biology subjects

Drevet, G.

Publications and source records attributed to Drevet, G..

2 recordsLinked to original sources

PACMOS: an R package for Projection And Classification of Multi-Omic Samples

MotivationIntegrated multi-omic analyses have transformed our understanding of cancer biology, giving rise to data-driven molecular classifications that capture disease heterogeneity beyond conventional histopathology. Among these approaches, multi-omic factor analysis (MOFA), a multimodal extension of principal component analysis, has been widely used to identify sources of molecular variation across omic layers and classify samples into molecular groups. However, classifying query samples according to an existing MOFA-based classification remains challenging, as there is no validated computational method for projecting samples into pretrained MOFA latent factor spaces. ResultsWe present PACMOS, an R package that provides a generalizable approach to project query samples into pretrained MOFA latent factor spaces. We validate PACMOS using two cancer datasets with published MOFA-based classifications--lung neuroendocrine neoplasms and pleural mesothelioma--showing that PACMOS preserves the existing MOFA latent factor space while allowing query samples to be classified. Availability and implementationPACMOS is an open-source R package available at https://github.com/IARCbioinfo/PACMOS and archived on Zenodo at https://doi.org/10.5281/zenodo.20933824, along with installation instructions and a vignette. Supplementary informationSupplementary data are available in separate files. Key messagesO_LIPACMOS enables the projection of query cancer samples into pretrained multi-omic latent factor spaces. C_LIO_LIThe package supports both continuous and discrete classifications. C_LIO_LIPACMOS provides a reproducible, per-sample workflow implemented in an R package. C_LIO_LIPACMOS demonstrates robust performance on pleural mesothelioma and lung neuroendocrine tumor datasets. C_LI

bioinformatics↗

Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas

The pathogenesis of thymic epithelial tumors remains poorly elucidated. The PI3K/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II study reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell system\n\nWe analyzed protein expression and activation of key players of the Akt/mTOR pathway namely Akt, mTOR, and P70S6K in thirteen A, B and AB thymomas as well as in normal thymuses. While only Akt and the phospho-Akt were expressed in normal thymuses, both Akt and mTOR were activated, with B2 thymomas expressing higher level of activated phospho-Akt than A or AB subtypes. Phospho-P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas, we report the activation of Akt; mTOR and P70S6. Finally, we analyzed the effect of mTOR inhibitor on thymoma derived epithelial cells and showed that rapamycin (100 nM/ ml) significantly reduced cell proliferation.\n\nOur results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens for in vitro exploration of molecular abnormalities specific to rare thymic tumors.

cancer biology↗