Recently, it was found that most multiobjective particle swarm optimizers (MOPSOs) perform poorly when tackling many-objective optimization problems (MaOPs). This is mainly because the loss of selection pressure that occurs when updating the swarm. The number of nondominated individuals is substantially increased and the diversity maintenance mechanisms in MOPSOs always guide the particles to explore sparse regions of the search space. This behavior results in the final solutions being distributed loosely in objective space, but far away from the true Pareto-optimal front. To avoid the above scenario, this paper presents a balanceable fitness estimation method and a novel velocity update equation, to compose a novel MOPSO (NMPSO), which is shown to be more effective to tackle MaOPs. Moreover, an evolutionary search is further run on the external archive in order to provide another search pattern for evolution. The DTLZ and WFG test suites with 4-10 objectives are used to assess the performance of NMPSO. Our experiments indicate that NMPSO has superior performance over four current MOPSOs, and over four competitive multiobjective evolutionary algorithms (SPEA2-SDE, NSGA-III, MOEA/DD, and SRA), when solving most of the test problems adopted.

We analyze the passengers' traffic pattern for 1.58 million taxi trips of Shanghai, China. By employing the non-negative matrix factorization and optimization methods, we find that, people travel on workdays mainly for three purposes: commuting between home and workplace, traveling from workplace to workplace, and others such as leisure activities. Therefore, traffic flow in one area or between any pair of locations can be approximated by a linear combination of three basis flows, corresponding to the three purposes respectively. We name the coefficients in the linear combination as traffic powers, each of which indicates the strength of each basis flow. The traffic powers on different days are typically different even for the same location, due to the uncertainty of the human motion. Therefore, we provide a probability distribution function for the relative deviation of the traffic power. This distribution function is in terms of a series of functions for normalized binomial distributions. It can be well explained by statistical theories and is verified by empirical data. These findings are applicable in predicting the road traffic, tracing the traffic pattern and diagnosing the traffic related abnormal events. These results can also be used to infer land uses of urban area quite parsimoniously.

Motivation: The prediction of off-target mutations in CRISPR-Cas9 is a hot topic due to its relevance to gene editing research. Existing prediction methods have been developed; however, most of them just calculated scores based on mismatches to the guide sequence in CRISPR-Cas9. Therefore, the existing prediction methods are unable to scale and improve their performance with the rapid expansion of experimental data in CRISPR-Cas9. Moreover, the existing methods still cannot satisfy enough precision in off-target predictions for gene editing at the clinical level. Results: To address it, we design and implement two algorithms using deep neural networks to predict off-target mutations in CRISPR-Cas9 gene editing (i.e. deep convolutional neural network and deep feedforward neural network). The models were trained and tested on the recently released off-target dataset, CRISPOR dataset, for performance benchmark. Another off-target dataset identified by GUIDE-seq was adopted for additional evaluation. We demonstrate that convolutional neural network achieves the best performance on CRISPOR dataset, yielding an average classification area under the ROC curve (AUC) of 97.2% under stratified 5-fold cross-validation. Interestingly, the deep feedforward neural network can also be competitive at the average AUC of 97.0% under the same setting. We compare the two deep neural network models with the state-of-the-art off-target prediction methods (i.e. CFD, MIT, CROP-IT, and CCTop) and three traditional machine learning models (i.e. random forest, gradient boosting trees, and logistic regression) on both datasets in terms of AUC values, demonstrating the competitive edges of the proposed algorithms. Additional analyses are conducted to investigate the underlying reasons from different perspectives. Availability and implementation: The example code are available at https://github.com/MichaelLinn/off_target_prediction. The related datasets are available at https://github.com/MichaelLinn/off_target_prediction/tree/master/data.

Structure-based generative chemistry is essential in computer-aided drug discovery by exploring a vast chemical space to design ligands with high binding affinity for targets. However, traditional in silico methods are limited by computational inefficiency, while machine learning approaches face bottlenecks due to auto-regressive sampling. To address these concerns, we have developed a conditional deep generative model, PMDM, for 3D molecule generation fitting specified targets. PMDM consists of a conditional equivariant diffusion model with both local and global molecular dynamics, enabling PMDM to consider the conditioned protein information to generate molecules efficiently. The comprehensive experiments indicate that PMDM outperforms baseline models across multiple evaluation metrics. To evaluate the applications of PMDM under real drug design scenarios, we conduct lead compound optimization for SARS-CoV-2 main protease (M^pro) and Cyclin-dependent Kinase 2 (CDK2), respectively. The selected lead optimization molecules are synthesized and evaluated for their in-vitro activities against CDK2, displaying improved CDK2 activity.

This paper suggests a novel clustering-based evolutionary algorithm for many-objective optimization problems. Its main idea is to classify the population into a number of clusters, which is expected to solve the difficulty of balancing convergence and diversity in high dimensional objective space. The individuals showing high similarities on the vector angles are gathered into the same cluster, such that the population’s distribution can be well portrayed by the clusters. To efficiently find these clusters, partitional clustering is first used to classify the union population into m main clusters based on the m axis vectors (m is the number of objectives), and then hierarchical clustering is further run on these m main clusters to get N final clusters (N is the population size and N > m). At last, in environmental selection, one individual from each of N clusters closest to the axis vectors is selected to maintain diversity, while one individual from each of the other clusters is preferred by a simple convergence indicator to ensure convergence. When tackling some well-known test problems with 5 to 15 objectives, extensive experiments validate the superiority of our algorithm over six competitive many-objective evolutionary algorithms, especially on problems with incomplete and irregular Pareto-optimal fronts.

The selection of swarm leaders (i.e., the personal best and global best), is important in the design of a multiobjective particle swarm optimization (MOPSO) algorithm. Such leaders are expected to effectively guide the swarm to approach the true Pareto optimal front. In this paper, we present a novel external archive-guided MOPSO algorithm (AgMOPSO), where the leaders for velocity update are all selected from the external archive. In our algorithm, multiobjective optimization problems (MOPs) are transformed into a set of subproblems using a decomposition approach, and then each particle is assigned accordingly to optimize each subproblem. A novel archive-guided velocity update method is designed to guide the swarm for exploration, and the external archive is also evolved using an immune-based evolutionary strategy. These proposed approaches speed up the convergence of AgMOPSO. The experimental results fully demonstrate the superiority of our proposed AgMOPSO in solving most of the test problems adopted, in terms of two commonly used performance measures. Moreover, the effectiveness of our proposed archive-guided velocity update method and immune-based evolutionary strategy is also experimentally validated on more than 30 test MOPs.