Rui Li

Kishan KC, Rui Li, Paribesh Regmi et al.

A biological system is a complex network of heterogeneous molecular entities and their interactions contributing to various biological characteristics of the system. However, current biological networks are noisy, sparse, and incomplete, limiting our ability to create a holistic view of the biological system and understand the biological phenomena. Experimental identification of such interactions is both time-consuming and expensive. With the recent advancements in high-throughput data generation and significant improvement in computational power, various computational methods have been developed to predict novel interactions in the noisy network. Recently, deep learning methods such as graph neural networks have shown their effectiveness in modeling graph-structured data and achieved good performance in biomedical interaction prediction. However, graph neural networks-based methods require human expertise and experimentation to design the appropriate complexity of the model and significantly impact the performance of the model. Furthermore, deep graph neural networks face overfitting problems and tend to be poorly calibrated with high confidence on incorrect predictions. To address these challenges, we propose Bayesian model selection for graph convolutional networks to jointly infer the most plausible number of graph convolution layers (depth) warranted by data and perform dropout regularization simultaneously. Experiments on four interaction datasets show that our proposed method achieves accurate and calibrated predictions. Our proposed method enables the graph convolutional networks to dynamically adapt their depths to accommodate an increasing number of interactions.

Rui Li, Francesco Belardinelli

The language of modal logic is capable of expressing first-order conditions on Kripke frames. The classic result by Henrik Sahlqvist identifies a significant class of modal formulas for which first-order conditions -- or Sahlqvist correspondents -- can be find in an effective, algorithmic way. Recent works have successfully extended this classic result to more complex modal languages. In this paper, we pursue a similar line and develop a Sahlqvist-style correspondence theorem for Linear-time Temporal Logic (LTL), which is one of the most widely used formal languages for temporal specification. LTL extends the syntax of basic modal logic with dedicated temporal operators Next X and Until U . As a result, the complexity of the class of formulas that have first-order correspondents also increases accordingly. In this paper, we identify a significant class of LTL Sahlqvist formulas built by using modal operators F , G, X, and U . The main result of this paper is to prove the correspondence of LTL Sahlqvist formulas to frame conditions that are definable in first-order language.

Jian Chen, Petra Isenberg, Robert S. Laramee et al.

We present and discuss the results of a qualitative analysis of visualization images to derive an image-based typology of visualizations. For each image, we seek to identify its main focus or the essential stimuli. As a result, we derived 10 image-based visualization types. We describe coding decisions we made in the derivation process. The resulting image typology can serve a number of purposes: enabling researchers and practitioners to identify visual design styles, facilitating the categorization of visualization images for the purpose of research and teaching, enabling researchers to study the evolution of the community and its research output over time, and facilitating a discussion of standardization in visualization. In addition, the tool and dataset enable scholars to closely examine the images and how they are published and communicated in our community. osf.io/dxjwt presents a pre-registration and all supplemental materials.

Zhongyue Zhang, Jiahua Rao, Jie Zhong et al.

Most human proteins remain undrugged, over 96% of human proteins remain unexploited by approved therapeutics. While structure-based virtual screening promises to expand the druggable proteome, existing methods lack atomic-level precision and fail to predict binding fitness, limiting translational impact. We present AuroBind, a scalable virtual screening framework that fine-tunes a custom atomic-level structural model on million-scale chemogenomic data. AuroBind integrates direct preference optimization, self-distillation from high-confidence complexes, and a teacher-student acceleration strategy to jointly predict ligand-bound structures and binding fitness. The proposed models outperform state-of-the-art models on structural and functional benchmarks while enabling 100,000-fold faster screening across ultra-large compound libraries. In a prospective screen across ten disease-relevant targets, AuroBind achieved experimental hit rates of 7-69%, with top compounds reaching sub-nanomolar to picomolar potency. For the orphan GPCRs GPR151 and GPR160, AuroBind identified both agonists and antagonists with success rates of 16-30%, and functional assays confirmed GPR160 modulation in liver and prostate cancer models. AuroBind offers a generalizable framework for structure-function learning and high-throughput molecular screening, bridging the gap between structure prediction and therapeutic discovery.

Hongyu Yang, Qi Zhao, Zhenhua hu et al.

Reinforcement Learning from Human Feedback and its variants excel in aligning with human intentions to generate helpful, harmless, and honest responses. However, most of them rely on costly human-annotated pairwise comparisons for supervised alignment, which is not suitable for list-level scenarios, such as community question answering. Additionally, human preferences are influenced by multiple intrinsic factors in responses, leading to decision-making inconsistencies. Therefore, we propose \textbf{Se}lf-supervised \textbf{A}ttribute-aware \textbf{d}ynamic \textbf{p}reference \textbf{ra}nking, called \shortname. \ It quantifies preference differences between responses based on Attribute-Perceptual Distance Factors (APDF) and dynamically determines the list-wise alignment order. Furthermore, it achieves fine-grained preference difference learning and enables precise alignment with the optimal one. We specifically constructed a challenging code preference dataset named StaCoCoQA, and introduced more cost-effective and scalable preference evaluation metrics: PrefHit and PrefRecall. Extensive experimental results show that SeAdpra exhibits superior performance and generalizability on both StaCoCoQA and preference datasets from eight popular domains.

Kishan KC, Feng Cui, Anne Haake et al.

Predicting protein-protein interactions (PPIs) by learning informative representations from amino acid sequences is a challenging yet important problem in biology. Although various deep learning models in Siamese architecture have been proposed to model PPIs from sequences, these methods are computationally expensive for a large number of PPIs due to the pairwise encoding process. Furthermore, these methods are difficult to interpret because of non-intuitive mappings from protein sequences to their sequence representation. To address these challenges, we present a novel deep framework to model and predict PPIs from sequence alone. Our model incorporates a bidirectional gated recurrent unit to learn sequence representations by leveraging contextualized and sequential information from sequences. We further employ a sparse regularization to model long-range dependencies between amino acids and to select important amino acids (protein motifs), thus enhancing interpretability. Besides, the novel design of the encoding process makes our model computationally efficient and scalable to an increasing number of interactions. Experimental results on up-to-date interaction datasets demonstrate that our model achieves superior performance compared to other state-of-the-art methods. Literature-based case studies illustrate the ability of our model to provide biological insights to interpret the predictions.

Jiaqi Zhao, Vitor Basto Fernandes, Licheng Jiao et al.

Finding a good classifier is a multiobjective optimization problem with different error rates and the costs to be minimized. The receiver operating characteristic is widely used in the machine learning community to analyze the performance of parametric classifiers or sets of Pareto optimal classifiers. In order to directly compare two sets of classifiers the area (or volume) under the convex hull can be used as a scalar indicator for the performance of a set of classifiers in receiver operating characteristic space. Recently, the convex hull based multiobjective genetic programming algorithm was proposed and successfully applied to maximize the convex hull area for binary classification problems. The contribution of this paper is to extend this algorithm for dealing with higher dimensional problem formulations. In particular, we discuss problems where parsimony (or classifier complexity) is stated as a third objective and multi-class classification with three different true classification rates to be maximized. The design of the algorithm proposed in this paper is inspired by indicator-based evolutionary algorithms, where first a performance indicator for a solution set is established and then a selection operator is designed that complies with the performance indicator. In this case, the performance indicator will be the volume under the convex hull. The algorithm is tested and analyzed in a proof of concept study on different benchmarks that are designed for measuring its capability to capture relevant parts of a convex hull. Further benchmark and application studies on email classification and feature selection round up the analysis and assess robustness and usefulness of the new algorithm in real world settings.