MOUSSE: Multi-Omics Using Subject-Specific SignaturEs

SIMPLE SUMMARY: Modern profiling technologies have led to relevant progress toward precision medicine and disease management. A new trend in patient classification is to integrate multiple data types for the same subjects to increase the chance of identifying meaningful phenotype groups. However, these methodologies are still in their infancy, with their performance varying widely depending on the biological conditions analyzed. We developed MOUSSE, a new unsupervised and normalization-free tool for multi-omics integration able to maintain good clustering performance across a wide range of omics data. We verified its efficiency in clustering patients based on survival for ten different cancer types. The results we obtained show a higher average score in classification performance than ten other state-of-the-art algorithms. We have further validated the method by identifying a list of biological features potentially involved in patient survival, finding a high degree of concordance with the literature. ABSTRACT: High-throughput technologies make it possible to produce a large amount of data representing different biological layers, examples of which are genomics, proteomics, metabolomics and transcriptomics. Omics data have been individually investigated to understand the molecular bases of various diseases, but this may not be sufficient to fully capture the molecular mechanisms and the multilayer regulatory processes underlying complex diseases, especially cancer. To overcome this problem, several multi-omics integration methods have been introduced but a commonly agreed standard of analysis is still lacking. In this paper, we present MOUSSE, a novel normalization-free pipeline for unsupervised multi-omics integration. The main innovations are the use of rank-based subject-specific signatures and the use of such signatures to derive subject similarity networks. A separate similarity network was derived for each omics, and the resulting networks were then carefully merged in a way that considered their informative content. We applied it to analyze survival in ten different types of cancer. We produced a meaningful clusterization of the subjects and obtained a higher average classification score than ten state-of-the-art algorithms tested on the same data. As further validation, we extracted from the subject-specific signatures a list of relevant features used for the clusterization and investigated their biological role in survival. We were able to verify that, according to the literature, these features are highly involved in cancer progression and differential survival.