In this paper, we focus on the study of evolutionary algorithms for solving multiobjective optimization problems with a large number of objectives. First, a comparative study of a newly developed dynamical multiobjective evolutionary algorithm (DMOEA) and some modern algorithms, such as the indicator-based evolutionary algorithm, multiple single objective Pareto sampling, and nondominated sorting genetic algorithm II, is presented by employing the convergence metric and relative hypervolume metric. For three scalable test problems (namely, DTLZ1, DTLZ2, and DTLZ6), which represent some of the most difficult problems studied in the literature, the DMOEA shows good performance in both converging to the true Pareto-optimal front and maintaining a widely distributed set of solutions. Second, a new definition of optimality (namely, L-optimality) is proposed in this paper, which not only takes into account the number of improved objective values but also considers the values of improved objective functions if all objectives have the same importance. We prove that L-optimal solutions are subsets of Pareto-optimal solutions. Finally, the new algorithm based on L-optimality (namely, MDMOEA) is developed, and simulation and comparative results indicate that well-distributed L-optimal solutions can be obtained by utilizing the MDMOEA but cannot be achieved by applying L-optimality to make a posteriori selection within the huge Pareto nondominated solutions. We can conclude that our new algorithm is suitable to tackle many-objective problems.

Significance: Microglia are the resident phagocytic cells of the central nervous system (CNS). During demyelination, a condition in which myelin sheaths are damaged and removed from neurons due to inflammation, microglia can play both harmful and beneficial roles, but their exact functions are still unclear. Using a drug that depletes microglia, we demonstrate that, after infection with JHMV, a coronavirus that infects the CNS of rodents and causes immune-mediated demyelination, microglia are essential for repair following demyelination. We found that microglia played critical roles in initiating this repair process by clearing myelin debris and producing prorepair factors, both of which promote the presence and the function of oligodendrocytes, the cells responsible for repairing and replacing myelin sheaths within areas of damage.

The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.

Background: This study aimed to develop an algorithm using the explainable artificial intelligence (XAI) approaches for the early prediction of mortality in intensive care unit (ICU) patients with acute kidney injury (AKI). Methods: This study gathered clinical data with AKI patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) in the US between 2008 and 2019. All the data were further randomly divided into a training cohort and a validation cohort. Seven machine learning methods were used to develop the models for assessing in-hospital mortality. The optimal model was selected based on its accuracy and area under the curve (AUC). The SHapley Additive exPlanation (SHAP) values and Local Interpretable Model-Agnostic Explanations (LIME) algorithm were utilized to interpret the optimal model. Results: A total of 22,360 patients with AKI were finally enrolled in this study (median age, 69.5 years; female, 42.8%). They were randomly split into a training cohort (16770, 75%) and a validation cohort (5590, 25%). The eXtreme Gradient Boosting (XGBoost) model achieved the best performance with an AUC of 0.890. The SHAP values showed that Glasgow Coma Scale (GCS), blood urea nitrogen, cumulative urine output on Day 1 and age were the top 4 most important variables contributing to the XGBoost model. The LIME algorithm was used to explain the individualized predictions. Conclusions: Machine-learning models based on clinical features were developed and validated with great performance for the early prediction of a high risk of death in patients with AKI.

To gain insights into the pathogenesis of influenza A virus (IAV) infections, this study focused on characterizing the inflammatory network and identifying key proteins by combining high-throughput data and computational techniques. We constructed the cell-specific normal and inflammatory networks for H5N1 and H1N1 infections through integrating high-throughput data. We demonstrated that better discrimination between normal and inflammatory networks by network entropy than by other topological metrics. Moreover, we identified different dynamical interactions among TLR2, IL-1β, IL10 and NFκB between normal and inflammatory networks using optimization algorithm. In particular, good robustness and multistability of inflammatory sub-networks were discovered. Furthermore, we identified a complex, TNFSF10/HDAC4/HDAC5, which may play important roles in controlling inflammation, and demonstrated that changes in network entropy of this complex negatively correlated to those of three proteins: TNFα, NFκB and COX-2. These findings provide significant hypotheses for further exploring the molecular mechanisms of infectious diseases and developing control strategies.

The identification of essential agents in multilayer networks characterized by different types of interactions is a crucial and challenging topic, one that is essential for understanding the topological structure and dynamic processes of multilayer networks. In this paper, we use the fourth-order tensor to represent multilayer networks and propose a novel method to identify essential nodes based on CANDECOMP/PARAFAC (CP) tensor decomposition, referred to as the EDCPTD centrality. This method is based on the perspective of multilayer networked structures, which integrate the information of edges among nodes and links between different layers to quantify the importance of nodes in multilayer networks. Three real-world multilayer biological networks are used to evaluate the performance of the EDCPTD centrality. The bar chart and ROC curves of these multilayer networks indicate that the proposed approach is a good alternative index to identify real important nodes. Meanwhile, by comparing the behavior of both the proposed method and the aggregated single-layer methods, we demonstrate that neglecting the multiple relationships between nodes may lead to incorrect identification of the most versatile nodes. Furthermore, the Gene Ontology functional annotation demonstrates that the identified top nodes based on the proposed approach play a significant role in many vital biological processes. Finally, we have implemented many centrality methods of multilayer networks (including our method and the published methods) and created a visual software based on the MATLAB GUI, called ENMNFinder, which can be used by other researchers.