Tosoni, Deniz David
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RWD-Cockpit. Application for quality assessment of real-world data
2022-10-18, Degen, Markus, Babrak, Lmar, Smakaj, Erand, Agac, Teyfik, Asprion, Petra, Grimberg, Frank, Van der Werf, Daan, Van Ginkel, Erwin Willem, Tosoni, Deniz David, Clay, Ieuan, Brodbeck, Dominique, Natali, Eriberto, Schkommodau, Erik, Miho, Enkelejda
Digital technologies are transforming the health care system. A large part of information is generated as real-world data (RWD). Data from electronic health records and digital biomarkers have the potential to reveal associations between the benefits and adverse events of medicines, establish new patient-stratification principles, expose unknown disease correlations, and inform on preventive measures. The impact for health care payers and providers, the biopharmaceutical industry, and governments is massive in terms of health outcomes, quality of care, and cost. However, a framework to assess the preliminary quality of RWD is missing, thus hindering the conduct of population-based observational studies to support regulatory decision-making and real-world evidence.
Machine learning detects anti-DENV signatures in antibody repertoire sequences
2021-10-11, Horst, Alexander, Smakaj, Erand, Natali, Eriberto, Tosoni, Deniz David, Babrak, Lmar, Meier, Patrick, Miho, Enkelejda
Dengue infection is a global threat. As of today, there is no universal dengue fever treatment or vaccines unreservedly recommended by the World Health Organization. The investigation of the specific immune response to dengue virus would support antibody discovery as therapeutics for passive immunization and vaccine design. High-throughput sequencing enables the identification of the multitude of antibodies elicited in response to dengue infection at the sequence level. Artificial intelligence can mine the complex data generated and has the potential to uncover patterns in entire antibody repertoires and detect signatures distinctive of single virus-binding antibodies. However, these machine learning have not been harnessed to determine the immune response to dengue virus. In order to enable the application of machine learning, we have benchmarked existing methods for encoding biological and chemical knowledge as inputs and have investigated novel encoding techniques. We have applied different machine learning methods such as neural networks, random forests, and support vector machines and have investigated the parameter space to determine best performing algorithms for the detection and prediction of antibody patterns at the repertoire and antibody sequence levels in dengue-infected individuals. Our results show that immune response signatures to dengue are detectable both at the antibody repertoire and at the antibody sequence levels. By combining machine learning with phylogenies and network analysis, we generated novel sequences that present dengue-binding specific signatures. These results might aid further antibody discovery and support vaccine design.
Benchmarking immunoinformatic tools for the analysis of antibody repertoire sequences
2019-12-24, Smakaj, Erand, Babrak, Lmar, Tosoni, Deniz David, Galli, Christa, Miho, Enkelejda