AI Meets Multi-Omics: Enabling Precision Medicine

Large quantities of heterogeneous, interconnected, systems-level, molecular (multi-omic) data are increasingly becoming available. They provide complementary information about cells, tissues and diseases. We need to utilize them to better stratify patients into risk groups, discover new biomarkers and targets, re-purpose known and discover new drugs to personalize medical treatment. This is nontrivial, because of computational intractability of many underlying problems on large interconnected data (networks, or graphs), necessitating the development of new algorithms for finding approximate solutions (heuristics) [1].

We develop a versatile data fusion artificial intelligence (AI) framework, that also utilizes the state-of-the-art network science methods, to address key challenges in precision medicine from the multi-omics data: better stratification of patients, prediction of biomarkers and targets, and re-purposing of approved drugs to particular patient groups, applied to different types of cancer [2,3], Covid-19 [4,5], Parkinson’s [6] and other diseases. Our new methods stem from graph-regularized non-negative matrix tri-factorization (NMTF), a machine learning technique for dimensionality reduction, inference and co-clustering of heterogeneous datasets, coupled with novel network science algorithms. We utilize our new frameworks to develop methodologies for improving the understanding the molecular organization and diseases from the omics data embedding spaces [7,8,9].


[1] NataÅ¡a Pržulj, Noel Malod-Dognin: “Network analytics in the age of big data”, Science 353 (6295) 123-124, 2016
[2] Noël Malod-Dognin, Julia Petschnigg, Sam FL Windels, Janez Povh, Harry Hemingway, Robin Ketteler, NataÅ¡a Pržulj, “Towards a data-integrated cell,” Nature Communications, 10 (1) 805, 2019
[3] Vladimir Gligorijević, Noël Malod-Dognin, NataÅ¡a Pržulj, “Patient-specific data fusion for cancer stratification and personalised treatment,” Biocomputing 2016: Proceedings of the Pacific Symposium, 2016
[4] Alexandros Xenos, Noël Malod-Dognin, Carme Zambrana, NataÅ¡a Pržulj, “Integrated data analysis uncovers new COVID-19 related genes and potential drug re-purposing candidates,” International Journal of Molecular Sciences, 24 (2) 1431, 2023
[5] Carme Zambrana, Alexandros Xenos, René Böttcher, Noël Malod-Dognin, NataÅ¡a Pržulj, “Network neighbors of viral targets and differentially expressed genes in COVID-19 are drug target candidates,” Scientific Reports, 11 (1) 18985, 2021
[6] Katarina Mihajlović, Gaia Ceddia, Nöel Malod-Dognin, Gabriela Novak, Dimitrios Kyriakis, Alexander Skupin, NataÅ¡a Pržulj, “Multi-omics integration of scRNA-seq time series data predicts new intervention points for Parkinson's disease,” bioRxiv 2023.12. 12.570554, 2023
[7] Alexandros Xenos, Noël Malod-Dognin, Stevan Milinković, NataÅ¡a Pržulj, “Linear functional organization of the omic embedding space,” Bioinformatics, 37 (21) 3839-3847, 2021
[8] Sergio Doria-Belenguer, Alexandros Xenos, Gaia Ceddia, Noël Malod-Dognin, NataÅ¡a Pržulj, “A functional analysis of omic network embedding spaces reveals key altered functions in cancer,” Bioinformatics, 39 (5) btad281, 2023
[9] Sergio Doria-Belenguer, Alexandros Xenos, Gaia Ceddia, Nöel Malod-Dognin, NataÅ¡a Pržulj, “The axes of biology: a novel axes-based network embedding paradigm to decipher the functional mechanisms of the cell,” bioRxiv, 2023.07.