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Drug-target interaction (DTI) prediction is a challenging, albeit essential task in drug repurposing. Learning on graph models have drawn special attention as they can significantly reduce drug repurposing costs and time commitment. However, many current approaches require high-demanding additional information besides DTIs that complicates their evaluation process and usability. Additionally, structural differences in the learning architecture of current models hinder their fair benchmarking. In this work, we first perform an in-depth evaluation of current DTI datasets and prediction models through a robust benchmarking process, and show that DTI prediction methods based on transductive models lack generalization and lead to inflated performance when evaluated as previously done in the literature, hence not being suited for drug repurposing approaches. We then propose a novel biologically-driven strategy for negative edge subsampling and show through in vitro validation that newly discovered interactions are indeed true. We envision this work as the underpinning for future fair benchmarking and robust model design. All generated resources and tools are publicly available as a python package.

Youth experiencing homelessness (YEH) are subject to substantially greater risk of HIV infection, compounded both by their lack of access to stable housing and the disproportionate representation of youth of marginalized racial, ethnic, and gender identity groups among YEH. A key goal for health equity is to improve adoption of protective behaviors in this population. One promising strategy for intervention is to recruit peer leaders from the population of YEH to promote behaviors such as condom usage and regular HIV testing to their social contacts. This raises a computational question: which youth should be selected as peer leaders to maximize the overall impact of the intervention? We developed an artificial intelligence system to optimize such social network interventions in a community health setting. We conducted a clinical trial enrolling 713 YEH at drop-in centers in a large US city. The clinical trial compared interventions planned with the algorithm to those where the highest-degree nodes in the youths' social network were recruited as peer leaders (the standard method in public health) and to an observation-only control group. Results from the clinical trial show that youth in the AI group experience statistically significant reductions in key risk behaviors for HIV transmission, while those in the other groups do not. This provides, to our knowledge, the first empirical validation of the usage of AI methods to optimize social network interventions for health. We conclude by discussing lessons learned over the course of the project which may inform future attempts to use AI in community-level interventions.

Each year, there are nearly 4 million youth experiencing homelessness (YEH) in the United States with HIV prevalence ranging from 3 to 11.5%. Peer change agent (PCA) models for HIV prevention have been used successfully in many populations, but there have been notable failures. In recent years, network interventionists have suggested that these failures could be attributed to PCA selection procedures. The change agents themselves who are selected to do the PCA work can often be as important as the messages they convey. To address this concern, we tested a new PCA intervention for YEH, with three arms: (1) an arm using an artificial intelligence (AI) planning algorithm to select PCA, (2) a popularity arm--the standard PCA approach--operationalized as highest degree centrality (DC), and (3) an observation only comparison group (OBS). PCA models that promote HIV testing, HIV knowledge, and condom use are efficacious for YEH. Both the AI and DC arms showed improvements over time. AI-based PCA selection led to better outcomes and increased the speed of intervention effects. Specifically, the changes in behavior observed in the AI arm occurred by 1 month, but not until 3 months in the DC arm. Given the transient nature of YEH and the high risk for HIV infection, more rapid intervention effects are desirable.