Doctor of Philosophy, Case Western Reserve University, 2023, EECS - Computer and Information Sciences

This dissertation presents a comprehensive approach to advancing proteomics and under-studied proteins in network biology, emphasizing the development of reliable algorithms, fair evaluation practices, and accessible computational tools. A key contribution of this work is the introduction of RoKAI, a novel algorithm that integrates multiple sources of functional information to infer kinase activity. By capturing coordinated changes in signaling pathways, RoKAI significantly improves kinase activity inference, facilitating the identification of dysregulated kinases in diseases. This enables deeper insights into cellular signaling networks, supporting targeted therapy development and expanding our understanding of disease mechanisms. To ensure fairness in algorithm evaluation, this research carefully examines potential biases arising from the under-representation of under-studied proteins and proposes strategies to mitigate these biases, promoting a more comprehensive evaluation and encouraging the discovery of novel findings. Additionally, this dissertation focuses on enhancing accessibility by developing user-friendly computational tools. The RoKAI web application provides a convenient and intuitive interface to perform RoKAI analysis. Moreover, RokaiXplorer web tool simplifies proteomic and phospho-proteomic data analysis for researchers without specialized expertise. It enables tasks such as normalization, statistical testing, pathway enrichment, provides interactive visualizations, while also offering researchers the ability to deploy their own data browsers, promoting the sharing of findings and fostering collaborations. Overall, this interdisciplinary research contributes to proteomics and network biology by providing robust algorithms, fair evaluation practices, and accessible tools. It lays the foundation for further advancements in the field, bringing us closer to uncovering new biomarkers and potential therapeutic targets in diseases like cancer, Alzheimer' (open full item for complete abstract)

Committee: Mehmet Koyutürk (Committee Chair); Mark Chance (Committee Member); Vincenzo Liberatore (Committee Member); Kevin Xu (Committee Member); Michael Lewicki (Committee Member) Subjects: Bioinformatics; Biomedical Research; Computer Science