Anastasia Baryshnikova

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  Mapping drug mode-of-action via functional analysis of large-scale biological networks
  Anastasia Baryshnikova

  In our quest for curing disease and improving the quality of human lives, we strive to understand what causes biological systems to break and how we can repair them. Large-scale biological networks are essential to this process as they map functional connections between most genes in the genome and can potentially uncover high level organizing principles governing cellular functions. To investigate network organization in normal and diseased conditions, I developed a systematic quantitative approach that measures the distribution of functional attributes across a network and maps their relative positioning. Using this approach on the global genetic and protein-protein interaction networks in yeast, I showed that genes acting in the same pathway, complex or biological process form coherent functional clusters, which localize close to one other according to their shared functionality and organize hierarchically. Furthermore, this approach provided a unique perspective onto the reproducibility of large-scale chemical genomic screens in yeast and revealed a novel link between vesicle-mediate transport and resistance to the anti-cancer drug bortezomib.