inh
- North America > United States > New York (0.04)
- Europe > United Kingdom > England > Oxfordshire > Oxford (0.04)
- Europe > Spain > Catalonia > Barcelona Province > Barcelona (0.04)
- Europe > Spain > Canary Islands > Gran Canaria (0.04)
Modeling Path Importance for Effective Alzheimer's Disease Drug Repurposing
Xiang, Shunian, Lawrence, Patrick J., Peng, Bo, Chiang, ChienWei, Kim, Dokyoon, Shen, Li, Ning, Xia
Recently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex networks that integrate multiple interaction types, such as protein-protein interactions, to more effectively identify candidate drugs. However, existing approaches typically assume paths of the same length in the network have equal importance in identifying the therapeutic effect of drugs. Other domains have found that same length paths do not necessarily have the same importance. Thus, relying on this assumption may be deleterious to drug repurposing attempts. In this work, we propose MPI (Modeling Path Importance), a novel network-based method for AD drug repurposing. MPI is unique in that it prioritizes important paths via learned node embeddings, which can effectively capture a network's rich structural information. Thus, leveraging learned embeddings allows MPI to effectively differentiate the importance among paths. We evaluate MPI against a commonly used baseline method that identifies anti-AD drug candidates primarily based on the shortest paths between drugs and AD in the network. We observe that among the top-50 ranked drugs, MPI prioritizes 20.0% more drugs with anti-AD evidence compared to the baseline. Finally, Cox proportional-hazard models produced from insurance claims data aid us in identifying the use of etodolac, nicotine, and BBB-crossing ACE-INHs as having a reduced risk of AD, suggesting such drugs may be viable candidates for repurposing and should be explored further in future studies.
- North America > United States > Pennsylvania > Philadelphia County > Philadelphia (0.14)
- North America > United States > Ohio > Franklin County > Columbus (0.04)
- Asia > Middle East > Iran > Tehran Province > Tehran (0.04)
- Research Report > New Finding (1.00)
- Research Report > Experimental Study (1.00)
Adding Default Attributes to EL++
Bonatti, Piero A. (Universita') | Faella, Marco (di Napoli Federico II) | Sauro, Luigi (Universita')
The research on low-complexity nonmonotonic description logics recently identified a fragment of EL with bottom, supporting defeasible inheritance with overriding, where reasoning can be carried out in polynomial time. We contribute to that framework by supporting more axiom schemata and all the concept constructors of EL++ without increasing asymptotic complexity. Moreover, we show that all the syntactic restrictions we adopt are necessary by proving several coNP-hardness results.