Thesis of Anna Bauer: Integrative approaches to investigate the molecular basis of diseases and adverse drug reactions: from multivariate statistical analysis to systems biology.

Anna Bauer, member of the Integrative Bioinformatics laboratory of GRIB (IMIM/ UPF) will defence her thesis the 8th of november at 11:30 at PRBB Auditorium.

Anna Bauer, member of the Integrative Bioinformatics laboratory of GRIB (IMIM/ UPF) will defence her thesis the 8th of november at 11:30 at PRBB Auditorium.

Summary

Despite some great success, many human diseases cannot be effectively treated, prevented or cured, yet. Moreover, prescribed drugs are often not very efficient and cause undesired side effects. Hence, there is a need to investigate the molecular basis of diseases and adverse drug reactions in more detail. For this purpose, relevant biomedical data needs to be gathered, integrated and analysed in a meaningful way.

In this regard, we have developed novel integrative analysis approaches based on both perspectives, classical multivariate statistics and systems biology. A novel multilevel statistical method has been developed for exploiting molecular and pharmacological information for a set of drugs in order to investigate undesired side effects. Systems biology approaches have been used to study the genetic basis of human diseases at a global scale. For this purpose, we have developed an integrated gene-disease association database and tools for user-friendly access and analysis. We showed that modularity applies for mendelian, complex and environmental diseases and identified disease-related core biological processes. We have constructed a workflow to investigate adverse drug reactions using our gene-disease association database. A detailed study of currently available pathway data has been performed to evaluate its applicability to build network models. Finally, a strategy to integrate information about sequence variations with biological pathways has been implemented to study the effect of the sequence variations onto biological processes.

In summary, the developed methods are of immense practical value for other biomedical researchers and can aid to improve the understanding of the molecular basis of diseases and adverse drug reactions.