Christopher Henry

Matthew Sinclair, Moeen Meigooni, Archit Vasan et al.

Intrinsically disordered proteins (IDPs) represent crucial therapeutic targets due to their significant role in disease -- approximately 80\% of cancer-related proteins contain long disordered regions -- but their lack of stable secondary/tertiary structures makes them "undruggable". While recent computational advances, such as diffusion models, can design high-affinity IDP binders, translating these to practical drug discovery requires autonomous systems capable of reasoning across complex conformational ensembles and orchestrating diverse computational tools at scale.To address this challenge, we designed and implemented StructBioReasoner, a scalable multi-agent system for designing biologics that can be used to target IDPs. StructBioReasoner employs a novel tournament-based reasoning framework where specialized agents compete to generate and refine therapeutic hypotheses, naturally distributing computational load for efficient exploration of the vast design space. Agents integrate domain knowledge with access to literature synthesis, AI-structure prediction, molecular simulations, and stability analysis, coordinating their execution on HPC infrastructure via an extensible federated agentic middleware, Academy. We benchmark StructBioReasoner across Der f 21 and NMNAT-2 and demonstrate that over 50\% of 787 designed and validated candidates for Der f 21 outperformed the human-designed reference binders from literature, in terms of improved binding free energy. For the more challenging NMNAT-2 protein, we identified three binding modes from 97,066 binders, including the well-studied NMNAT2:p53 interface. Thus, StructBioReasoner lays the groundwork for agentic reasoning systems for IDP therapeutic discovery on Exascale platforms.

Mikhail Sokolov, Christopher Henry, Joni Storie et al.

Deep learning has become one of remote sensing scientists' most efficient computer vision tools in recent years. However, the lack of training labels for the remote sensing datasets means that scientists need to solve the domain adaptation problem to narrow the discrepancy between satellite image datasets. As a result, image segmentation models that are then trained, could better generalize and use an existing set of labels instead of requiring new ones. This work proposes an unsupervised domain adaptation model that preserves semantic consistency and per-pixel quality for the images during the style-transferring phase. This paper's major contribution is proposing the improved architecture of the SemI2I model, which significantly boosts the proposed model's performance and makes it competitive with the state-of-the-art CyCADA model. A second contribution is testing the CyCADA model on the remote sensing multi-band datasets such as WorldView-2 and SPOT-6. The proposed model preserves semantic consistency and per-pixel quality for the images during the style-transferring phase. Thus, the semantic segmentation model, trained on the adapted images, shows substantial performance gain compared to the SemI2I model and reaches similar results as the state-of-the-art CyCADA model. The future development of the proposed method could include ecological domain transfer, {\em a priori} evaluation of dataset quality in terms of data distribution, or exploration of the inner architecture of the domain adaptation model.

Andrew M. Nagel, Anne Webster, Christopher Henry et al.

In Canada's northern regions, linear disturbances such as roads, seismic exploration lines, and pipelines pose a significant threat to the boreal woodland caribou population (Rangifer tarandus). To address the critical need for management of these disturbances, there is a strong emphasis on developing mapping approaches that accurately identify forest habitat fragmentation. The traditional approach is manually generating maps, which is time-consuming and lacks the capability for frequent updates. Instead, applying deep learning methods to multispectral satellite imagery offers a cost-effective solution for automated and regularly updated map production. Deep learning models have shown promise in extracting paved roads in urban environments when paired with high-resolution (<0.5m) imagery, but their effectiveness for general linear feature extraction in forested areas from lower resolution imagery remains underexplored. This research employs a deep convolutional neural network model based on the VGGNet16 architecture for semantic segmentation of lower resolution (10m) Sentinel-2 satellite imagery, creating precise multi-class linear disturbance maps. The model is trained using ground-truth label maps sourced from the freely available Alberta Institute of Biodiversity Monitoring Human Footprint dataset, specifically targeting the Boreal and Taiga Plains ecozones in Alberta, Canada. Despite challenges in segmenting lower resolution imagery, particularly for thin linear disturbances like seismic exploration lines that can exhibit a width of 1-3 pixels in Sentinel-2 imagery, our results demonstrate the effectiveness of the VGGNet model for accurate linear disturbance retrieval. By leveraging the freely available Sentinel-2 imagery, this work advances cost-effective automated mapping techniques for identifying and monitoring linear disturbance fragmentation.