Multi-omic analysis and integration with prior knowledge to study signalling and metabolism deregulations in cancer cell lines
Mentor: Aurelien Dugourd
Overview:
Overview:
Multi-omics datasets can provide molecular insights beyond the sum of individual omics. Various tools have been recently developed to integrate such datasets, but there are limited strategies to systematically extract mechanistic hypotheses from them. Here, we present COSMOS (Causal Oriented Search of Multi-Omics Space, https://github.com/saezlab/cosmosR), a method that integrates phosphoproteomics, transcriptomics, and metabolomics datasets. COSMOS combines extensive prior knowledge of signalling, metabolic, and gene regulatory networks with computational methods to estimate activities of transcription factors and kinases as well as network-level causal reasoning. COSMOS provides mechanistic hypotheses for experimental observations across multi-omics datasets, leveraging prior knowledge such as signalling events, ligand-receptor interactions and metabolic networks. The concepts behind COSMOS are presented, including its latest advances, notably its integration with factor based analysis tools such as MOFA.
GitHub page for the project: https://github.com/saezlab/Factor_COSMOS/tree/no_MOFA
Project aims:
- Explore NCI60 cell line omic datasets
- Interpreting TF activities estimated from RNA seq data
- Learning to use cosmos to integrate signalling and metabolic data with prior knowledge
- Generate and interpret testable hypotheses
Suggested reading:
- Kim J & DeBerardinis RJ (2019) Mechanisms and Implications of Metabolic Heterogeneity in Cancer. Cell Metab 30: 434–446
- Su G, Burant CF, Beecher CW, Athey BD & Meng F (2011) Integrated metabolome and transcriptome analysis of the NCI60 dataset. BMC Bioinformatics 12 Suppl 1: S36
- Badia-i-Mompel P, Vélez J, Braunger J, Geiss C, Dimitrov D, Müller-Dott S, Taus P, Dugourd A, Holland CH, Ramirez Flores RO, et al (2021) decoupleR: Ensemble of computational methods to infer biological activities from omics data. bioRxiv: 2021.11.04.467271
- Dugourd A & Saez-Rodriguez J (2019) Footprint-based functional analysis of multiomic data. Curr Opin Syst Biol 15: 82–90
- Dugourd A, Kuppe C, Sciacovelli M, Gjerga E, Gabor A, Emdal KB, Vieira V, Bekker-Jensen DB, Kranz J, Bindels EMJ, et al (2021) Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses. Mol Syst Biol 17: e9730