PathIntegrate: Multivariate modelling approaches for pathway-based multi-omics data integration

As terabytes of multi-omics data are being generated, there is an ever-increasing need for methods facilitating the integration and interpretation of such data. Current multi-omics integration methods typically output lists, clusters, or subnetworks of molecules related to an outcome. Even with expert domain knowledge, discerning the biological processes involved is a time-consuming activity. Here we propose PathIntegrate, a method for integrating multi-omics datasets based on pathways, designed to exploit knowledge of biological systems and thus provide interpretable models for such studies. PathIntegrate employs single-sample pathway analysis to transform multi-omics datasets from the molecular to the pathway-level, and applies a predictive single-view or multi-view model to integrate the data. Model outputs include multi-omics pathways ranked by their contribution to the outcome prediction, the contribution of each omics layer, and the importance of each molecule in a pathway. Using semi-synthetic data we demonstrate the benefit of grouping molecules into pathways to detect signals in low signal-to-noise scenarios, as well as the ability of PathIntegrate to precisely identify important pathways at low effect sizes. Finally, using COPD and COVID-19 data we showcase how PathIntegrate enables convenient integration and interpretation of complex high-dimensional multi-omics datasets. PathIntegrate is available as an open-source Python package. Omics data, which provides a readout of the levels of molecules such as genes, proteins, and metabolites in a sample, is frequently generated to study biological processes and perturbations within an organism. Combining multiple omics data types can provide a more comprehensive understanding of the underlying biology, making it possible to piece together how different molecules interact. There exist many software packages designed to integrate multi-omics data, but interpreting the resulting outputs remains a challenge. Placing molecules into the context of biological pathways enables us to better understand their collective functions and understand how they may contribute to the condition under study. We have developed PathIntegrate, a pathway-based multi-omics integration tool which helps integrate and interpret multi-omics data in a single step using machine learning. By integrating data at the pathway rather than the molecular level, the relationships between molecules in pathways can be strengthened and more readily identified. PathIntegrate is demonstrated on Chronic Obstructive Pulmonary Disease and COVID-19 metabolomics, proteomics, and transcriptomics datasets, showcasing its ability to efficiently extract perturbed multi-omics pathways from large-scale datasets.