In multi-objective black-box optimization, the goal is typically to find solutions that optimize a set of $T$ black-box objective functions, $f_1, \ldots f_T$, simultaneously. Traditional approaches often seek a single Pareto-optimal set that balances trade-offs among all objectives. In contrast, we consider a problem setting that departs from this paradigm: finding a small set of $K < T$ solutions, that collectively "cover" the $T$ objectives. A set of solutions is defined as "covering" if, for each objective $f_1, \ldots f_T$, there is at least one good solution. A motivating example for this problem setting occurs in drug design. For example, we may have $T$ pathogens and aim to identify a set of $K < T$ antibiotics such that at least one antibiotic can be used to treat each pathogen. This problem, known as coverage optimization, has yet to be tackled with the Bayesian optimization (BO) framework. To fill this void, we develop Multi-Objective Coverage Bayesian Optimization (MOCOBO), a BO algorithm for solving coverage optimization. Our approach is based on a new acquisition function reminiscent of expected improvement in the vanilla BO setup. We demonstrate the performance of our method on high-dimensional black-box optimization tasks, including applications in peptide and molecular design. Results show that the coverage of the $K < T$ solutions found by MOCOBO matches or nearly matches the coverage of $T$ solutions obtained by optimizing each objective individually. Furthermore, in *in vitro* experiments, the peptides found by MOCOBO exhibited high potency against drug-resistant pathogens, further demonstrating the potential of MOCOBO for drug discovery. All of our code is publicly available at the following link: https://github.com/nataliemaus/mocobo.

The recent boom in single-cell sequencing technologies provides valuable insights into the transcriptomes of individual cells. Through single-cell data analyses, a number of biological discoveries, such as novel cell types, developmental cell lineage trajectories, and gene regulatory networks, have been uncovered. However, the massive and increasingly accumulated single-cell datasets have also posed a seriously computational and analytical challenge for researchers. To address this issue, one typically applies dimensionality reduction approaches to reduce the large-scale datasets. However, these approaches are generally computationally infeasible for tall matrices. In addition, the downstream data analysis tasks such as clustering still take a large time complexity even on the dimension-reduced datasets. We present single-cell Coreset (scCoreset), a data summarization framework that extracts a small weighted subset of cells from a huge sparse single-cell RNA-seq data to facilitate the downstream data analysis tasks. Single-cell data analyses run on the extracted subset yield similar results to those derived from the original uncompressed data. Tests on various single-cell datasets show that scCoreset outperforms the existing data summarization approaches for common downstream tasks such as visualization and clustering. We believe that scCoreset can serve as a useful plug-in tool to improve the efficiency of current single-cell RNA-seq data analyses.

MOTIVATION: Quantitative structure-activity relationship (QSAR) and drug-target interaction (DTI) prediction are both commonly used in drug discovery. Collaboration among pharmaceutical institutions can lead to better performance in both QSAR and DTI prediction. However, the drug-related data privacy and intellectual property issues have become a noticeable hindrance for inter-institutional collaboration in drug discovery. RESULTS: We have developed two novel algorithms under secure multiparty computation (MPC), including QSARMPC and DTIMPC, which enable pharmaceutical institutions to achieve high-quality collaboration to advance drug discovery without divulging private drug-related information. QSARMPC, a neural network model under MPC, displays good scalability and performance and is feasible for privacy-preserving collaboration on large-scale QSAR prediction. DTIMPC integrates drug-related heterogeneous network data and accurately predicts novel DTIs, while keeping the drug information confidential. Under several experimental settings that reflect the situations in real drug discovery scenarios, we have demonstrated that DTIMPC possesses significant performance improvement over the baseline methods, generates novel DTI predictions with supporting evidence from the literature and shows the feasible scalability to handle growing DTI data. All these results indicate that QSARMPC and DTIMPC can provide practically useful tools for advancing privacy-preserving drug discovery. AVAILABILITY AND IMPLEMENTATION: The source codes of QSARMPC and DTIMPC are available on the GitHub: https://github.com/rongma6/QSARMPC_DTIMPC.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Prediction of peptide binding to the major histocompatibility complex (MHC) plays a vital role in the development of therapeutic vaccines for the treatment of cancer. Algorithms with improved correlations between predicted and actual binding affinities are needed to increase precision and reduce the number of false positive predictions. RESULTS: We present ACME (Attention-based Convolutional neural networks for MHC Epitope binding prediction), a new pan-specific algorithm to accurately predict the binding affinities between peptides and MHC class I molecules, even for those new alleles that are not seen in the training data. Extensive tests have demonstrated that ACME can significantly outperform other state-of-the-art prediction methods with an increase of the Pearson correlation coefficient between predicted and measured binding affinities by up to 23 percentage points. In addition, its ability to identify strong-binding peptides has been experimentally validated. Moreover, by integrating the convolutional neural network with attention mechanism, ACME is able to extract interpretable patterns that can provide useful and detailed insights into the binding preferences between peptides and their MHC partners. All these results have demonstrated that ACME can provide a powerful and practically useful tool for the studies of peptide-MHC class I interactions. AVAILABILITY AND IMPLEMENTATION: ACME is available as an open source software at https://github.com/HYsxe/ACME. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Motivation: Accurately predicting drug-target interactions (DTIs) in silico can guide the drug discovery process and thus facilitate drug development. Computational approaches for DTI prediction that adopt the systems biology perspective generally exploit the rationale that the properties of drugs and targets can be characterized by their functional roles in biological networks. Results: Inspired by recent advance of information passing and aggregation techniques that generalize the convolution neural networks to mine large-scale graph data and greatly improve the performance of many network-related prediction tasks, we develop a new nonlinear end-to-end learning model, called NeoDTI, that integrates diverse information from heterogeneous network data and automatically learns topology-preserving representations of drugs and targets to facilitate DTI prediction. The substantial prediction performance improvement over other state-of-the-art DTI prediction methods as well as several novel predicted DTIs with evidence supports from previous studies have demonstrated the superior predictive power of NeoDTI. In addition, NeoDTI is robust against a wide range of choices of hyperparameters and is ready to integrate more drug and target related information (e.g. compound-protein binding affinity data). All these results suggest that NeoDTI can offer a powerful and robust tool for drug development and drug repositioning. Availability and implementation: The source code and data used in NeoDTI are available at: https://github.com/FangpingWan/NeoDTI. Supplementary information: Supplementary data are available at Bioinformatics online.