Multi-target drug discovery has become an essential strategy for treating complex diseases involving multiple molecular pathways. Traditional single-target approaches often fall short in addressing the multifactorial nature of conditions such as cancer and neurodegenerative disorders. With the rise in large-scale biological data and algorithmic advances, machine learning (ML) has emerged as a powerful tool to accelerate and optimize multi-target drug development. This review presents a comprehensive overview of ML techniques, including advanced deep learning (DL) approaches like attention-based models, and highlights their application in multi-target prediction, from traditional supervised learning to modern graph-based and multi-task learning frameworks. We highlight real-world applications in oncology, central nervous system disorders, and drug repurposing, showcasing the translational potential of ML in systems pharmacology. Major challenges are discussed, such as data sparsity, lack of interpretability, limited generalizability, and integration into experimental workflows. We also address ethical and regulatory considerations surrounding model transparency, fairness, and reproducibility. Looking forward, we explore promising directions such as generative modeling, federated learning, and patient-specific therapy design. Together, these advances point toward a future of precision polypharmacology driven by biologically informed and interpretable ML models. This review aims to provide researchers and practitioners with a roadmap for leveraging ML in the development of safer and more effective multi-target therapeutics.

Cancer’s heterogeneity presents significant challenges in accurate diagnosis and effective treatment, including the complexity of identifying tumor subtypes and their diverse biological behaviors. This review examines how feature selection techniques address these challenges by improving the interpretability and performance of machine learning (ML) models in high-dimensional datasets. Feature selection methods—such as filter, wrapper, and embedded techniques—play a critical role in enhancing the precision of cancer diagnostics by identifying relevant biomarkers. The integration of multi-omics data and ML algorithms facilitates a more comprehensive understanding of tumor heterogeneity, advancing both diagnostics and personalized therapies. However, challenges such as ensuring data quality, mitigating overfitting, and addressing scalability remain critical limitations of these methods. Artificial intelligence (AI)-powered feature selection offers promising solutions to these issues by automating and refining the feature extraction process. This review highlights the transformative potential of these approaches while emphasizing future directions, including the incorporation of deep learning (DL) models and integrative multi-omics strategies for more robust and reproducible findings.

Osteoporosis (OP) is a metabolic bone disorder characterized by low bone mass and deterioration of micro-architectural bone tissue. The most common type of OP is postmenopausal osteoporosis (PMOP), with fragility fractures becoming a global burden for women. Recently, the gut microbiota has been connected to bone metabolism. The aim of this study was to characterize the gut microbiota signatures in PMOP patients and controls. Fecal samples from 21 PMOP patients and 37 controls were collected and analyzed using amplicon sequencing of the V3-V4 regions of the 16S rRNA gene. The bone mineral density (BMD) measurement and laboratory biochemical test were performed on all participants. Two feature selection algorithms, maximal information coefficient (MIC) and XGBoost, were employed to identify the PMOP-related microbial features. Results showed that the composition of gut microbiota changed in PMOP patients, and microbial abundances were more correlated with total hip BMD/T-score than lumbar spine BMD/T-score. Using the MIC and XGBoost methods, we identified a set of PMOP-related microbes; a logistic regression model revealed that two microbial markers (Fusobacteria and Lactobacillaceae) had significant abilities in disease classification between the PMOP and control groups. Taken together, the findings of this study provide new insights into the etiology of OP/PMOP, as well as modulating gut microbiota as a therapeutic target in the diseases. We also highlight the application of feature selection approaches in biological data mining and data analysis, which may improve the research in medical and life sciences.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Precise drug target discovery is pivotal to mitigating the escalating costs and high attrition rates that characterize pharmaceutical research and development. Given that traditional single-omics methods often fail to elucidate the systemic complexity of human diseases, deep learning (DL)-enabled multi-omics integration has emerged as a transformative frontier. This review systematically summarizes the advancements in DL-driven multi-omics integration for drug target discovery. First, the multi-omics data foundation and integration strategies are delineated, followed by an exploration of the DL architectures utilized for processing such data. Subsequently, the efficacy of DL-driven multi-omics integration is examined regarding the identification of novel disease drivers, prediction of synthetic lethality interactions, and prioritization of therapeutic targets. Finally, addressing persistent challenges related to data sparsity, model interpretability, and target druggability and validation hurdles, emerging opportunities driven by Generative AI, Large Multimodal Models (LMMs), Explainable AI (XAI), and multidimensional feasibility assessment frameworks are discussed in the context of advancing precision medicine.

Osteoporosis (OP), a systemic skeletal disease characterized by compromised bone strength and elevated fracture susceptibility, represents a growing global health challenge that necessitates early detection and accurate risk stratification. With the exponential growth of multidimensional biomedical data in OP research, feature selection has become an indispensable machine learning paradigm that improves model generalizability. At the same time, it preserves clinical interpretability and enhances predictive accuracy. This perspective article systematically reviews the transformative role of feature selection methodologies across 3 critical domains of OP investigation: (1) multi-omics biomarker identification, (2) diagnostic pattern recognition, and (3) fracture risk prognostication. In biomarker discovery, advanced feature selection algorithms systematically refine high-dimensional multi-omics datasets (genomic, proteomic, and metabolomic) to isolate key molecular signatures correlated with BMD trajectories and microarchitectural deterioration. For clinical diagnostics, these techniques enable efficient extraction of discriminative pattern from multimodal imaging data, including DXA, QCT, and emerging dental radiographic biomarkers. In prognostic modeling, strategic variable selection optimizes prognostic accuracy by integrating demographic, biochemical, and biomechanical predictors while mitigating overfitting in heterogeneous patient cohorts. Current challenges include heterogeneity in dataset quality and dimensionality, translational gaps between algorithmic outputs and clinical decision parameters, and limited reproducibility across diverse populations. Future directions should prioritize the development of adaptive feature selection frameworks capable of dynamic multi-omics data integration, coupled with hybrid intelligence systems that synergize machine-derived biomarkers with clinician expertise. Addressing these challenges requires coordinated interdisciplinary efforts to establish standardized validation protocols and create clinician-friendly decision support interfaces, ultimately bridging the gap between computational OP research and personalized patient care.