Protein-protein interaction (PPI) prediction is an instrumental means in elucidating the mechanisms underlying cellular operations, holding significant practical implications for the realms of pharmaceutical development and clinical treatment. Presently, the majority of research methods primarily concentrate on the analysis of amino acid sequences, while investigations predicated on protein structures remain in the nascent stages of exploration. Despite the emergence of several structure-based algorithms in recent years, these are still confronted with inherent challenges: (1) the extraction of intrinsic structural information of proteins typically necessitates the expenditure of substantial computational resources; (2) these models are overly reliant on seen protein data, struggling to effectively unearth interaction cues between unknown proteins. To further propel advancements in this domain, this paper introduces a novel PPI prediction method jointing masked reconstruction and contrastive learning, termed JmcPPI. This methodology dissects the PPI prediction task into two distinct phases: during the residue structure encoding phase, JmcPPI devises two feature reconstruction tasks and employs graph attention mechanism to capture structural information between residues; during the protein interaction inference phase, JmcPPI perturbs the original PPI graph and employs a multi-graph contrastive learning strategy to thoroughly mine extrinsic interaction information of novel proteins. Extensive experiments conducted on three widely utilized PPI datasets demonstrate that JmcPPI surpasses existing optimal baseline models across various data partition schemes. The associated code can be accessed via https://github.com/lijfrank-open/JmcPPI.

The analysis of high-dimensional timeline data and the identification of outliers and anomalies is critical across diverse domains, including sensor readings, biological and medical data, historical records, and global statistics. However, conventional analysis techniques often struggle with challenges such as high dimensionality, complex distributions, and sparsity. These limitations hinder the ability to extract meaningful insights from complex temporal datasets, making it difficult to identify trending features, outliers, and anomalies effectively. Inspired by surprisability -- a cognitive science concept describing how humans instinctively focus on unexpected deviations - we propose Learning via Surprisability (LvS), a novel approach for transforming high-dimensional timeline data. LvS quantifies and prioritizes anomalies in time-series data by formalizing deviations from expected behavior. LvS bridges cognitive theories of attention with computational methods, enabling the detection of anomalies and shifts in a way that preserves critical context, offering a new lens for interpreting complex datasets. We demonstrate the usefulness of LvS on three high-dimensional timeline use cases: a time series of sensor data, a global dataset of mortality causes over multiple years, and a textual corpus containing over two centuries of State of the Union Addresses by U.S. presidents. Our results show that the LvS transformation enables efficient and interpretable identification of outliers, anomalies, and the most variable features along the timeline.

In the rapidly advancing field of materials informatics, nonlinear machine learning models have demonstrated exceptional predictive capabilities for material properties. However, their black-box nature limits interpretability, and they may incorporate features that do not contribute to--or even deteriorate--model performance. This study employs explainable ML (XML) techniques, including permutation feature importance and the SHapley Additive exPlanation, applied to a pristine support vector regression model designed to predict band gaps at the GW level using 18 input features. Guided by XML-derived individual feature importance, a simple framework is proposed to construct reduced-feature predictive models. Model evaluations indicate that an XML-guided compact model, consisting of the top five features, achieves comparable accuracy to the pristine model on in-domain datasets while demonstrating superior generalization with lower prediction errors on out-of-domain data. Additionally, the study underscores the necessity for eliminating strongly correlated features to prevent misinterpretation and overestimation of feature importance before applying XML. This study highlights XML's effectiveness in developing simplified yet highly accurate machine learning models by clarifying feature roles.

Federated Averaging remains the most widely used aggregation strategy in federated learning due to its simplicity and scalability. However, its performance degrades significantly in non-IID data settings, where client distributions are highly imbalanced or skewed. Additionally, it relies on clients transmitting metadata, specifically the number of training samples, which introduces privacy risks and may conflict with regulatory frameworks like the European GDPR. In this paper, we propose a novel aggregation strategy that addresses these challenges by introducing class-aware gradient masking. Unlike traditional approaches, our method relies solely on gradient updates, eliminating the need for any additional client metadata, thereby enhancing privacy protection. Furthermore, our approach validates and dynamically weights client contributions based on class-specific importance, ensuring robustness against non-IID distributions, convergence prevention, and backdoor attacks. Extensive experiments on benchmark datasets demonstrate that our method not only outperforms FedAvg and other widely accepted aggregation strategies in non-IID settings but also preserves model integrity in adversarial scenarios. Our results establish the effectiveness of gradient masking as a practical and secure solution for federated learning.

Semi-supervised clustering is a basic problem in various applications. Most existing methods require knowledge of the ideal cluster number, which is often difficult to obtain in practice. Besides, satisfying the must-link constraints is another major challenge for these methods. In this work, we view the semi-supervised clustering task as a partitioning problem on a graph associated with the given dataset, where the similarity matrix includes a scaling parameter to reflect the must-link constraints. Utilizing a relaxation technique, we formulate the graph partitioning problem into a continuous optimization model that does not require the exact cluster number, but only an overestimate of it. We then propose a block coordinate descent algorithm to efficiently solve this model, and establish its convergence result. Based on the obtained solution, we can construct the clusters that theoretically meet the must-link constraints under mild assumptions. Furthermore, we verify the effectiveness and efficiency of our proposed method through comprehensive numerical experiments.

This research addresses the challenges of handling unbalanced datasets for binary classification tasks. In such scenarios, standard evaluation metrics are often biased by the disproportionate representation of the minority class. Conducting experiments across seven datasets, we uncovered inconsistencies in evaluation metrics when determining the model that outperforms others for each binary classification problem. This justifies the need for a metric that provides a more consistent and unbiased evaluation across unbalanced datasets, thereby supporting robust model selection. To mitigate this problem, we propose a novel metric, the Unbiased Integration Coefficients (UIC), which exhibits significantly reduced bias ($p < 10^{-4}$) towards the minority class compared to conventional metrics. The UIC is constructed by aggregating existing metrics while penalising those more prone to imbalance. In addition, we introduce the Identical Partitions for Imbalance Problems (IPIP) algorithm for imbalanced ML problems, an ensemble-based approach. Our experimental results show that IPIP outperforms other baseline imbalance-aware approaches using Random Forest and Logistic Regression models in three out of seven datasets as assessed by the UIC metric, demonstrating its effectiveness in addressing imbalanced data challenges in binary classification tasks. This new framework for dealing with imbalanced datasets is materialized in the FILM (Framework for Imbalanced Learning Machines) R Package, accessible at https://github.com/antoniogt/FILM.

Concept-based models are an emerging paradigm in deep learning that constrains the inference process to operate through human-interpretable concepts, facilitating explainability and human interaction. However, these architectures, on par with popular opaque neural models, fail to account for the true causal mechanisms underlying the target phenomena represented in the data. This hampers their ability to support causal reasoning tasks, limits out-of-distribution generalization, and hinders the implementation of fairness constraints. To overcome these issues, we propose \emph{Causally reliable Concept Bottleneck Models} (C$^2$BMs), a class of concept-based architectures that enforce reasoning through a bottleneck of concepts structured according to a model of the real-world causal mechanisms. We also introduce a pipeline to automatically learn this structure from observational data and \emph{unstructured} background knowledge (e.g., scientific literature). Experimental evidence suggest that C$^2$BM are more interpretable, causally reliable, and improve responsiveness to interventions w.r.t. standard opaque and concept-based models, while maintaining their accuracy.

Structure-based drug discovery (SBDD) is a systematic scientific process that develops new drugs by leveraging the detailed physical structure of the target protein. Recent advancements in pre-trained models for biomolecules have demonstrated remarkable success across various biochemical applications, including drug discovery and protein engineering. However, in most approaches, the pre-trained models primarily focus on the characteristics of either small molecules or proteins, without delving into their binding interactions which are essential cross-domain relationships pivotal to SBDD. To fill this gap, we propose a general-purpose foundation model named BIT (an abbreviation for Biomolecular Interaction Transformer), which is capable of encoding a range of biochemical entities, including small molecules, proteins, and protein-ligand complexes, as well as various data formats, encompassing both 2D and 3D structures. Specifically, we introduce Mixture-of-Domain-Experts (MoDE) to handle the biomolecules from diverse biochemical domains and Mixture-of-Structure-Experts (MoSE) to capture positional dependencies in the molecular structures. The proposed mixture-of-experts approach enables BIT to achieve both deep fusion and domain-specific encoding, effectively capturing fine-grained molecular interactions within protein-ligand complexes. Then, we perform cross-domain pre-training on the shared Transformer backbone via several unified self-supervised denoising tasks. Experimental results on various benchmarks demonstrate that BIT achieves exceptional performance in downstream tasks, including binding affinity prediction, structure-based virtual screening, and molecular property prediction.

Single-cell RNA sequencing (scRNA-seq) technology has profiled hundreds of millions of human cells across organs, diseases, development and perturbations to date. However, the high-dimensional sparsity, batch effect noise, category imbalance, and ever-increasing data scale of the original sequencing data pose significant challenges for multi-center knowledge transfer, data fusion, and cross-validation between scRNA-seq datasets. To address these barriers, (1) we first propose a latent codes-based scRNA-seq dataset distillation framework named scDD, which transfers and distills foundation model knowledge and original dataset information into a compact latent space and generates synthetic scRNA-seq dataset by a generator to replace the original dataset. Then, (2) we propose a single-step conditional diffusion generator named SCDG, which perform single-step gradient back-propagation to help scDD optimize distillation quality and avoid gradient decay caused by multi-step back-propagation. Meanwhile, SCDG ensures the scRNA-seq data characteristics and inter-class discriminability of the synthetic dataset through flexible conditional control and generation quality assurance. Finally, we propose a comprehensive benchmark to evaluate the performance of scRNA-seq dataset distillation in different data analysis tasks. It is validated that our proposed method can achieve 7.61% absolute and 15.70% relative improvement over previous state-of-the-art methods on average task.

Stochastic optimization methods have actively been playing a critical role in modern machine learning algorithms to deliver decent performance. While numerous works have proposed and developed diverse approaches, first-order and second-order methods are in entirely different situations. The former is significantly pivotal and dominating in emerging deep learning but only leads convergence to a stationary point. However, second-order methods are less popular due to their computational intensity in large-dimensional problems. This paper presents a novel method that leverages both the first-order and second-order methods in a unified algorithmic framework, termed FUSE, from which a practical version (PV) is derived accordingly. FUSE-PV stands as a simple yet efficient optimization method involving a switch-over between first and second orders. Additionally, we develop different criteria that determine when to switch. FUSE-PV has provably shown a smaller computational complexity than SGD and Adam. To validate our proposed scheme, we present an ablation study on several simple test functions and show a comparison with baselines for benchmark datasets.