Journal of Proteomics & Bioinformatics
Open Access

Phosphoproteomic-based systems pharmacology for drug discovery

5^th International Conference on Proteomics & Bioinformatics

September 01-03, 2015 Valencia, Spain

Leonidas G Alexopoulos1,2

1ProtATonce Ltd., Greece 2National Technical University of Athens, Greece

Posters-Accepted Abstracts: J Proteomics Bioinform

Abstract :

A major challenge for bringing safe and effective new treatment to patients is the deep understanding of a disease. Here, we describe the integration of multi-omics data with systems biology algorithms for tackling three milestones in the drug development process: Construction of pathways and comparison between normal or diseased cells; Identification of drug mode of action (MoA) and Prediction of drug toxicity and efficacy. On the experimental front, we develop custom multiplex proteomic and phosphoproteomic assays based on the Luminex technology. To guarantee the quality of the assays we quantify the cross-reactivity profile of antibodies and we have developed optimization algorithms to select the optimal pairs. Currently, a ~40x phosphoprotein panel and a ~80x cytokine panel have been developed. On the computational front, signaling cascades are modeled with a Boolean or fuzzy logic framework and signaling pathways or optimized in order to fit the phopshoproteomic data at hand. Then, knowing the cells topology, we monitor drug-induced topology alterations in order to reveal drug mode of action. Subsequently, supervised machine learning algorithms was able to select MoAs with reduced toxicity and increased efficacy. So far we have applied our approach in several diseases including liver cancer, osteoarthritis and multiple sclerosis.

Biography :

Email: leo@protatonce.com