As we migrate into an era of personalized medicine, understanding how bio-molecules interact with one another to form cellular systems is one of the key focus areas of systems biology. Several challenges such as the dynamic nature of cellular systems, uncertainty due to environmental influences, and the heterogeneity between individual patients render this a difficult task. In the last decade, several algorithms have been proposed to elucidate cellular systems from data, resulting in numerous data-driven hypotheses. However, due to the large number of variables involved in the process, many of which are unknown or not measurable, such computational approaches often lead to a high proportion of false positives. This renders interpretation of the data-driven hypotheses extremely difficult. Consequently, a dismal proportion of these hypotheses are subject to further experimental validation, eventually limiting their potential to augment existing biological knowledge. This dissertation develops a framework of computational methods for the analysis of such data-driven hypotheses leveraging existing biological knowledge. Specifically, I show how biological knowledge can be mapped onto these hypotheses and subsequently augmented through novel hypotheses. Biological hypotheses are learnt in three levels of abstraction -- individual interactions, functional modules and relationships between pathways, corresponding to three complementary aspects of biological systems. The computational methods developed in this dissertation are applied to high throughput cancer data, resulting in novel hypotheses with potentially significant biological impact.

Building computational models of human problem solving has been a longstanding goal in Artificial Intelligence research. The theories of cognitive architectures addressed this issue by embedding models of problem solving within them. This thesis presents an extended account of human problem solving and describes its implementation within one such theory of cognitive architecture--ICARUS. The document begins by reviewing the standard theory of problem solving, along with how previous versions of ICARUS have incorporated and expanded on it. Next it discusses some limitations of the existing mechanism and proposes four extensions that eliminate these limitations, elaborate the framework along interesting dimensions, and bring it into closer alignment with human problem-solving abilities. After this, it presents evaluations on four domains that establish the benefits of these extensions. The results demonstrate the system's ability to solve problems in various domains and its generality. In closing, it outlines related work and notes promising directions for additional research.