Network-based gene prioritization algorithms are designed to prioritize disease-associated genes based on known ones using biological networks of protein interactions, gene-disease associations (GDAs) and other relationships between biological entities. Various algorithms have been developed based on different mechanisms, but it is not obvious which algorithm is optimal for a specific disease. To address this issue, we benchmarked multiple algorithms for their application in cerebral small vessel disease (cSVD). We curated protein-gene interactions (PGIs) and GDAs from databases and assembled PGI networks and disease-gene heterogeneous networks. A screening of algorithms resulted in seven representative algorithms to be benchmarked. Performance of algorithms was assessed using both leave-one-out cross-validation (LOOCV) and external validation with MEGASTROKE genome-wide association study (GWAS). We found that random walk with restart on the heterogeneous network (RWRH) showed best LOOCV performance, with median LOOCV rediscovery rank of 185.5 (out of 19 463 genes). The GenePanda algorithm had most GWAS-confirmable genes in top 200 predictions, while RWRH had best ranks for small vessel stroke-associated genes confirmed in GWAS. In conclusion, RWRH has overall better performance for application in cSVD despite its susceptibility to bias caused by degree centrality. Choice of algorithms should be determined before applying to specific disease. Current pure network-based gene prioritization algorithms are unlikely to find novel disease-associated genes that are not associated with known ones. The tools for implementing and benchmarking algorithms have been made available and can be generalized for other diseases.

Fabric is a modular and extensible open-source system for deploying and operating permissioned blockchains and one of the Hyperledger projects hosted by the Linux Foundation (www.hyperledger.org).

Global positioning systems have enabled the accurate measurement of very large distances and in conjunction with ubiquitous wifi hotspots have enabled the widespread adoption of location based tourism applications which utilise online mapping services to provide users with accurate directions. This paper documents an ‘E-Local Advisor’ application which provides street maps, directions and location of local services. The application works by receiving GPS signals which interact with online mapping services through outdoor wifi hotspots. Tourists can locate places of interest, find out where they are and query the system for exact directions from one location to another.