spb/wp44_uqo

1{"work_id": 4388522045, "title": "SRplot: A free online platform for data visualization and graphing", "abstract": "Graphics are widely used to provide summarization of complex data in scientific publications. Although there are many tools available for drawing graphics, their use is limited by programming skills, costs, and platform specificities. Here, we presented a freely accessible easy-to-use web server named SRplot that integrated more than a hundred of commonly used data visualization and graphing functions together. It can be run easily using all Web browsers and there are no strong requirements on the computing power of users' machines. With a user-friendly graphical interface, users can simply paste the contents of the input file into the text box according to the defined file format. Modification operations can be easily performed, and graphs can be generated in real-time. The resulting graphs can be easily downloaded in bitmap (PNG or TIFF) or vector (PDF or SVG) format in publication quality. The website is updated promptly and continuously. Functions in SRplot have been improved, optimized and updated depend on feedback and suggestions from users. The graphs prepared with SRplot have been featured in more than five hundred peer-reviewed publications. The SRplot web server is now freely available at http://www.bioinformatics.com.cn/SRplot."}2{"work_id": 4319754774, "title": "Acceptance of artificial intelligence in teaching science: Science teachers' perspective", "abstract": "Over the last few decades, there has been growing interest in artificial intelligence (AI) and how to apply it effectively in the educational process. The behavioural intention and attitudes of teachers play an important role in this regard. The technology acceptance model (TAM) has been shown to be effective in predicting factors that may positively or negatively influence behavioural intentions to use technology. The current study therefore aims to use this model to reveal teachers\u2019 perceptions of the factors that influence the use of AI applications in science education. This research uses the descriptive method where a 6-dimensional scale is designed based on the components of the TAM model and then applied to a sample of 83 science teachers in Abu Dhabi. The results show a high acceptability of the use of AI in the classroom by science teachers, with positive correlations to self-efficacy, ease of use, expected benefits, attitudes, and behavioural intentions. However, anxiety and stress do not significantly affect other factors. Regarding the predictive power of research models, the combined factors expected benefits, ease of use, and attitude toward AI applications can predict 71.4% of future behavioural changes related to the use of AI applications in science teaching. This study finds no statistically significant differences in teacher responses based on the variables gender, teaching experience, and qualifications regarding teachers\u2019 behavioural intentions to actually use AI in science teaching."}3{"work_id": 4416043407, "title": "Accelerating scientific discovery with Co-Scientist", "abstract": "Abstract Scientific discovery is driven by scientists generating hypotheses for complex problems that undergo rigorous experimental validation. To augment this process, we introduce Co-Scientist, a multi-agent artificial intelligence (AI) system built on Gemini for structured scientific thinking and hypothesis generation. Co-Scientist aims to help scientists discover new original knowledge. Conditioned on their research objectives and previous scientific evidence, it formulates demonstrably novel research hypotheses for experimental verification. The system\u2019s design involves agents continuously generating, critiquing and refining hypotheses accelerated by scaling test-time compute. Key contributions include (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling, and (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute scaling, improving hypothesis quality over time. Although this is a general-purpose system, we focus the validation in three biomedical applications: drug repurposing; novel-target discovery 1 ; and explaining mechanisms of antimicrobial resistance 2 . Specifically, Co-Scientist helped to identify new drug-repurposing candidates and synergistic combination therapies for acute myeloid leukaemia that were validated through in vitro experiments. These real-world validations demonstrate the potential of Co-Scientist to accelerate scientific discovery and usher in an era of AI-empowered scientists."}4{"work_id": 3210165781, "title": "Artificial intelligence: A powerful paradigm for scientific research", "abstract": "Artificial intelligence (AI) coupled with promising machine learning (ML) techniques well known from computer science is broadly affecting many aspects of various fields including science and technology, industry, and even our day-to-day life. The ML techniques have been developed to analyze high-throughput data with a view to obtaining useful insights, categorizing, predicting, and making evidence-based decisions in novel ways, which will promote the growth of novel applications and fuel the sustainable booming of AI. This paper undertakes a comprehensive survey on the development and application of AI in different aspects of fundamental sciences, including information science, mathematics, medical science, materials science, geoscience, life science, physics, and chemistry. The challenges that each discipline of science meets, and the potentials of AI techniques to handle these challenges, are discussed in detail. Moreover, we shed light on new research trends entailing the integration of AI into each scientific discipline. The aim of this paper is to provide a broad research guideline on fundamental sciences with potential infusion of AI, to help motivate researchers to deeply understand the state-of-the-art applications of AI-based fundamental sciences, and thereby to help promote the continuous development of these fundamental sciences."}5{"work_id": 4385811703, "title": "Accelerating Manufacturing Decisions using Bayesian Optimization: An Optimization and Prediction Perspective", "abstract": "Manufacturing is a promising technique for producing complex and custom-made parts with a high degree of precision. It can also provide us with desired materials and products with specified properties. To achieve that, it is crucial to find out the optimum point of process parameters that have a significant impact on the properties and quality of the final product. Unfortunately, optimizing these parameters can be challenging due to the complex and nonlinear nature of the underlying process, which becomes more complicated when there are conflicting objectives, sometimes with multiple goals. Furthermore, experiments are usually costly, time-consuming, and require expensive materials, man, and machine hours. So, each experiment is valuable and it's critical to determine the optimal experiment location to gain the most comprehensive understanding of the process. Sequential learning is a promising approach to actively learn from the ongoing experiments, iteratively update the underlying optimization routine, and adapt the data collection process on the go. This thesis presents a multi-objective Bayesian optimization framework to find out the optimum processing conditions for a manufacturing setup. It uses an acquisition function to collect data points sequentially and iteratively update its understanding of the underlying design space utilizing a Gaussian Process-based surrogate model. In manufacturing processes, the focus is often on obtaining a rough understanding of the design space using minimal experimentation, rather than finding the optimal parameters. This falls under the category of \"approximating the underlying function\" rather than design optimization. This approach can provide material scientists or manufacturing engineers with a comprehensive view of the entire design space, increasing the likelihood of making discoveries or making robust decisions. However, a precise and reliable prediction model is necessary for a good approximation. To meet this requirement, this thesis proposes an epsilon-greedy sequential prediction framework that is distinct from the optimization framework. The data acquisition strategy has been refined to balance exploration and exploitation, and a threshold has been established to determine when to switch between the two. The performance of this proposed optimization and prediction framework is evaluated using real-life datasets against the traditional design of experiments. The proposed frameworks have generated effective optimization and prediction results using fewer experiments."}6{"work_id": 2789843538, "title": "Minimap2: pairwise alignment for nucleotide sequences", "abstract": "Motivation: Recent advances in sequencing technologies promise ultra-long reads of \u223c100 kb in average, full-length mRNA or cDNA reads in high throughput and genomic contigs over 100 Mb in length. Existing alignment programs are unable or inefficient to process such data at scale, which presses for the development of new alignment algorithms. Results: Minimap2 is a general-purpose alignment program to map DNA or long mRNA sequences against a large reference database. It works with accurate short reads of \u2265100 bp in length, \u22651 kb genomic reads at error rate \u223c15%, full-length noisy Direct RNA or cDNA reads and assembly contigs or closely related full chromosomes of hundreds of megabases in length. Minimap2 does split-read alignment, employs concave gap cost for long insertions and deletions and introduces new heuristics to reduce spurious alignments. It is 3-4 times as fast as mainstream short-read mappers at comparable accuracy, and is \u226530 times faster than long-read genomic or cDNA mappers at higher accuracy, surpassing most aligners specialized in one type of alignment. Availability and implementation: https://github.com/lh3/minimap2. Supplementary information: Supplementary data are available at Bioinformatics online."}7{"work_id": 2888532099, "title": "The Astropy Project: Building an Open-science Project and Status of the v2.0 Core Package *", "abstract": "Abstract The Astropy Project supports and fosters the development of open-source and openly developed Python packages that provide commonly needed functionality to the astronomical community. A key element of the Astropy Project is the core package astropy , which serves as the foundation for more specialized projects and packages. In this article, we provide an overview of the organization of the Astropy project and summarize key features in the core package, as of the recent major release, version 2.0. We then describe the project infrastructure designed to facilitate and support development for a broader ecosystem of interoperable packages. We conclude with a future outlook of planned new features and directions for the broader Astropy Project."}8{"work_id": 4411463597, "title": "Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction", "abstract": "Accurately modeling biomolecular interactions is a central challenge in modern biology. While recent advances, such as AlphaFold3 and Boltz-1, have substantially improved our ability to predict biomolecular complex structures, these models still fall short in predicting binding affinity, a critical property underlying molecular function and therapeutic efficacy. Here, we present Boltz-2, a new structural biology foundation model that exhibits strong performance for both structure and affinity prediction. Boltz-2 introduces controllability features including experimental method conditioning, distance constraints, and multi-chain template integration for structure prediction, and is, to our knowledge, the first AI model to approach the performance of free-energy perturbation (FEP) methods in estimating small molecule-protein binding affinity. Crucially, it achieves strong correlation with experimental readouts on many benchmarks, while being at least 1000\u00d7 more computationally efficient than FEP. By coupling Boltz-2 with a generative model for small molecules, we demonstrate an effective workflow to find diverse, synthesizable, high-affinity binders, as estimated by absolute FEP simulations on the TYK2 target. To foster broad adoption and further innovation at the intersection of machine learning and biology, we are releasing Boltz-2 weights, inference, and training code under a permissive open license, providing a robust and extensible foundation for both academic and industrial research."}9{"work_id": 3201073812, "title": "LAMMPS - a flexible simulation tool for particle-based materials modeling at the atomic, meso, and continuum scales", "abstract": "Since the classical molecular dynamics simulator LAMMPS was released as an open source code in 2004, it has become a widely-used tool for particle-based modeling of materials at length scales ranging from atomic to mesoscale to continuum. Reasons for its popularity are that it provides a wide variety of particle interaction models for different materials, that it runs on any platform from a single CPU core to the largest supercomputers with accelerators, and that it gives users control over simulation details, either via the input script or by adding code for new interatomic potentials, constraints, diagnostics, or other features needed for their models. As a result, hundreds of people have contributed new capabilities to LAMMPS and it has grown from fifty thousand lines of code in 2004 to a million lines today. In this paper several of the fundamental algorithms used in LAMMPS are described along with the design strategies which have made it flexible for both users and developers. We also highlight some capabilities recently added to the code which were enabled by this flexibility, including dynamic load balancing, on-the-fly visualization, magnetic spin dynamics models, and quantum-accuracy machine learning interatomic potentials. Program Title: Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) CPC Library link to program files: https://doi.org/10.17632/cxbxs9btsv.1 Developer's repository link: https://github.com/lammps/lammps Licensing provisions: GPLv2 Programming language: C++, Python, C, Fortran Supplementary material: https://www.lammps.org Nature of problem: Many science applications in physics, chemistry, materials science, and related fields require parallel, scalable, and efficient generation of long, stable classical particle dynamics trajectories. Within this common problem definition, there lies a great diversity of use cases, distinguished by different particle interaction models, external constraints, as well as timescales and lengthscales ranging from atomic to mesoscale to macroscopic. Solution method: The LAMMPS code uses parallel spatial decomposition, distributed neighbor lists, and parallel FFTs for long-range Coulombic interactions [1]. The time integration algorithm is based on the St\u00f8rmer-Verlet symplectic integrator [2], which provides better stability than higher-order non-symplectic methods. In addition, LAMMPS supports a wide range of interatomic potentials, constraints, diagnostics, software interfaces, and pre- and post-processing features. Additional comments including restrictions and unusual features: This paper serves as the definitive reference for the LAMMPS code. S. Plimpton, Fast parallel algorithms for short-range molecular dynamics. J. Comp. Phys. 117 (1995) 1\u201319. L. Verlet, Computer experiments on classical fluids: I. Thermodynamical properties of Lennard\u2013Jones molecules, Phys. Rev. 159 (1967) 98\u2013103."}10{"work_id": 7125546963, "title": "Artificial intelligence and machine learning guided optimization in drug delivery", "abstract": "The optimisation of drug delivery systems is a complex, multidimensional challenge involving the interplay of formulation composition, process parameters, and biological performance. Traditional empirical and statistical approaches are increasingly limited by the high dimensionality, nonlinearity, and multi-objective nature of modern drug delivery problems. In this review, we explore how artificial intelligence (AI) and machine learning (ML) are transforming formulation science by enabling data-driven, adaptive, and efficient optimisation strategies. We provide a conceptual and practical overview of ML-guided optimisation workflows, including surrogate modelling, Bayesian optimisation, active learning, and multi-objective optimisation. Key challenges such as data scarcity, experimental throughput, and model interpretability are discussed. Applications across diverse delivery modalities, including solid oral dosage forms, lipid nanoparticles, biologics, and long-acting injectables, are critically examined, highlighting how ML can accelerate formulation development, reduce experimental burden, and uncover novel design spaces. We conclude by outlining future directions for integrating AI into pharmaceutical R&D, with a focus on the emergence of self-driving laboratories. This review aims to equip drug delivery scientists with the foundational knowledge and practical tools to harness AI and ML in the rational design and optimisation of advanced drug delivery systems."}11{"work_id": 4390940921, "title": "Solving olympiad geometry without human demonstrations", "abstract": "Abstract Proving mathematical theorems at the olympiad level represents a notable milestone in human-level automated reasoning 1\u20134 , owing to their reputed difficulty among the world\u2019s best talents in pre-university mathematics. Current machine-learning approaches, however, are not applicable to most mathematical domains owing to the high cost of translating human proofs into machine-verifiable format. The problem is even worse for geometry because of its unique translation challenges 1,5 , resulting in severe scarcity of training data. We propose AlphaGeometry, a theorem prover for Euclidean plane geometry that sidesteps the need for human demonstrations by synthesizing millions of theorems and proofs across different levels of complexity. AlphaGeometry is a neuro-symbolic system that uses a neural language model, trained from scratch on our large-scale synthetic data, to guide a symbolic deduction engine through infinite branching points in challenging problems. On a test set of 30 latest olympiad-level problems, AlphaGeometry solves 25, outperforming the previous best method that only solves ten problems and approaching the performance of an average International Mathematical Olympiad (IMO) gold medallist. Notably, AlphaGeometry produces human-readable proofs, solves all geometry problems in the IMO 2000 and 2015 under human expert evaluation and discovers a generalized version of a translated IMO theorem in 2004."}12{"work_id": 2951939904, "title": "Jointly Embedding Multiple Single-Cell Omics Measurements", "abstract": "Many single-cell sequencing technologies are now available, but it is still difficult to apply multiple sequencing technologies to the same single cell. In this paper, we propose an unsupervised manifold alignment algorithm, MMD-MA, for integrating multiple measurements carried out on disjoint aliquots of a given population of cells. Effectively, MMD-MA performs an in silico co-assay by embedding cells measured in different ways into a learned latent space. In the MMD-MA algorithm, single-cell data points from multiple domains are aligned by optimizing an objective function with three components: (1) a maximum mean discrepancy (MMD) term to encourage the differently measured points to have similar distributions in the latent space, (2) a distortion term to preserve the structure of the data between the input space and the latent space, and (3) a penalty term to avoid collapse to a trivial solution. Notably, MMD-MA does not require any correspondence information across data modalities, either between the cells or between the features. Furthermore, MMD-MA\u2019s weak distributional requirements for the domains to be aligned allow the algorithm to integrate heterogeneous types of single cell measures, such as gene expression, DNA accessibility, chromatin organization, methylation, and imaging data. We demonstrate the utility of MMD-MA in simulation experiments and using a real data set involving single-cell gene expression and methylation data."}13{"work_id": 4410552772, "title": "ASKCOS: Open-Source, Data-Driven Synthesis Planning", "abstract": "ConspectusThe advancement of machine learning and the availability of large-scale reaction datasets have accelerated the development of data-driven models for computer-aided synthesis planning (CASP) in the past decade. In this Account, we describe the range of data-driven methods and models that have been incorporated into the newest version of ASKCOS, an open-source software suite for synthesis planning that we have been developing since 2016. This ongoing effort has been driven by the importance of bridging the gap between research and development, making research advances available through a freely available practical tool. ASKCOS integrates modules for retrosynthetic planning, modules for complementary capabilities of condition prediction and reaction product prediction, and several supplementary modules and utilities with various roles in synthesis planning. For retrosynthetic planning, we have developed an Interactive Path Planner (IPP) for user-guided search as well as a Tree Builder for automatic planning with two well-known tree search algorithms, Monte Carlo Tree Search (MCTS) and Retro*. Four one-step retrosynthesis models covering template-based and template-free strategies form the basis of retrosynthetic predictions and can be used simultaneously to combine their advantages and propose diverse suggestions. Strategies for assessing the feasibility of proposed reaction steps and evaluating the full pathways are built on top of several pioneering efforts that we have made in the subtasks of reaction condition recommendation, pathway scoring and clustering, and the prediction of reaction outcomes including the major product, impurities, site selectivity, and regioselectivity. In addition, we have also developed auxiliary capabilities in ASKCOS based on our past and ongoing work for solubility prediction and quantum mechanical descriptor prediction, which can provide more insight into the suitability of proposed reaction solvents or the hypothetical selectivity of desired transformations. For each of these capabilities, we highlight its relevance in the context of synthesis planning and present a comprehensive overview of how it is built on top of not only our work but also of other recent advancements in the field. We also describe in detail how chemists can easily interact with these capabilities via user-friendly interfaces. ASKCOS has assisted hundreds of medicinal, synthetic, and process chemists in their day-to-day tasks by complementing expert decision making and route ideation. It is our belief that CASP tools are an important part of modern chemistry research and offer ever-increasing utility and accessibility."}14{"work_id": 4288039037, "title": "Scientific Machine Learning Through Physics\u2013Informed Neural Networks: Where we are and What\u2019s Next", "abstract": "Abstract Physics-Informed Neural Networks (PINN) are neural networks (NNs) that encode model equations, like Partial Differential Equations (PDE), as a component of the neural network itself. PINNs are nowadays used to solve PDEs, fractional equations, integral-differential equations, and stochastic PDEs. This novel methodology has arisen as a multi-task learning framework in which a NN must fit observed data while reducing a PDE residual. This article provides a comprehensive review of the literature on PINNs: while the primary goal of the study was to characterize these networks and their related advantages and disadvantages. The review also attempts to incorporate publications on a broader range of collocation-based physics informed neural networks, which stars form the vanilla PINN, as well as many other variants, such as physics-constrained neural networks (PCNN), variational hp-VPINN, and conservative PINN (CPINN). The study indicates that most research has focused on customizing the PINN through different activation functions, gradient optimization techniques, neural network structures, and loss function structures. Despite the wide range of applications for which PINNs have been used, by demonstrating their ability to be more feasible in some contexts than classical numerical techniques like Finite Element Method (FEM), advancements are still possible, most notably theoretical issues that remain unresolved."}15{"work_id": 2927961455, "title": "Interactive Tree Of Life (iTOL) v4: recent updates and new developments", "abstract": "The Interactive Tree Of Life (https://itol.embl.de) is an online tool for the display, manipulation and annotation of phylogenetic and other trees. It is freely available and open to everyone. The current version introduces four new dataset types, together with numerous new features. Annotation options have been expanded and new control options added for many display elements. An interactive spreadsheet-like editor has been implemented, providing dataset creation and editing directly in the web interface. Font support has been rewritten with full support for UTF-8 character encoding throughout the user interface. Google Web Fonts are now fully supported in the tree text labels. iTOL v4 is the first tool which supports direct visualization of Qiime 2 trees and associated annotations. The user account system has been streamlined and expanded with new navigation options, and currently handles >700 000 trees from more than 40 000 individual users. Full batch access has been implemented allowing programmatic upload and export of trees and annotations."}16{"work_id": 4386373863, "title": "PyMC: a modern, and comprehensive probabilistic programming framework in Python", "abstract": "PyMC is a probabilistic programming library for Python that provides tools for constructing and fitting Bayesian models. It offers an intuitive, readable syntax that is close to the natural syntax statisticians use to describe models. PyMC leverages the symbolic computation library PyTensor, allowing it to be compiled into a variety of computational backends, such as C, JAX, and Numba, which in turn offer access to different computational architectures including CPU, GPU, and TPU. Being a general modeling framework, PyMC supports a variety of models including generalized hierarchical linear regression and classification, time series, ordinary differential equations (ODEs), and non-parametric models such as Gaussian processes (GPs). We demonstrate PyMC's versatility and ease of use with examples spanning a range of common statistical models. Additionally, we discuss the positive role of PyMC in the development of the open-source ecosystem for probabilistic programming."}17{"work_id": 3098269892, "title": "Automatic Chemical Design Using a Data-Driven Continuous Representation of Molecules.", "abstract": "We report a method to convert discrete representations of molecules to and from a multidimensional continuous representation. This model allows us to generate new molecules for efficient exploration and optimization through open-ended spaces of chemical compounds. A deep neural network was trained on hundreds of thousands of existing chemical structures to construct three coupled functions: an encoder, a decoder, and a predictor. The encoder converts the discrete representation of a molecule into a real-valued continuous vector, and the decoder converts these continuous vectors back to discrete molecular representations. The predictor estimates chemical properties from the latent continuous vector representation of the molecule. Continuous representations of molecules allow us to automatically generate novel chemical structures by performing simple operations in the latent space, such as decoding random vectors, perturbing known chemical structures, or interpolating between molecules. Continuous representations also allow the use of powerful gradient-based optimization to efficiently guide the search for optimized functional compounds. We demonstrate our method in the domain of drug-like molecules and also in a set of molecules with fewer that nine heavy atoms."}18{"work_id": 2899070097, "title": "PubChem 2019 update: improved access to chemical data", "abstract": "PubChem (https://pubchem.ncbi.nlm.nih.gov) is a key chemical information resource for the biomedical research community. Substantial improvements were made in the past few years. New data content was added, including spectral information, scientific articles mentioning chemicals, and information for food and agricultural chemicals. PubChem released new web interfaces, such as PubChem Target View page, Sources page, Bioactivity dyad pages and Patent View page. PubChem also released a major update to PubChem Widgets and introduced a new programmatic access interface, called PUG-View. This paper describes these new developments in PubChem."}19{"work_id": 4400064820, "title": "Less can be more for predicting properties with large language models", "abstract": "Abstract Predicting properties from coordinate\u2013category data\u2014sets of vectors paired with categorical information\u2014is fundamental to computational science, manifesting in materials science as predicting formation energies or elastic moduli from crystal structures. While large language models (LLMs) have increasingly been applied to such tasks, optimal strategies for achieving reliable predictions remain elusive. Here we report fundamental limitations in LLM\u2019s ability to learn from coordinate information in coordinate\u2013category data. Through systematic experiments using synthetic datasets with tunable coordinate and category contributions, and a comprehensive benchmarking framework (MatText), we find that LLMs consistently fail to capture coordinate information while excelling at category patterns. This geometric blindness persists regardless of model size (up to 70 billion parameters), dataset scale (up to 2 \u00d7 10 6 structures) or text representation strategy. For material property prediction tasks dominated by structural effects, specialized geometric architectures consistently outperform LLMs, as evidenced by a clear \u2018Graph Neural Network Language Model (GNN-LM) wall\u2019 in performance benchmarks. Our analysis provides concrete guidelines for architecture selection in scientific machine learning."}20{"work_id": 3011072970, "title": "Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2", "abstract": "Abstract Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the \u2018 Complementary Exposure\u2019 pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs."}21{"work_id": 3008142620, "title": "Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods", "abstract": "SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections."}22{"work_id": 3161540023, "title": "Visualizations with statistical details: The 'ggstatsplot' approach", "abstract": "Graphical displays can reveal problems in a statistical model that might not be apparent from purely numerical summaries.Such visualizations can also be helpful for the reader to evaluate the validity of a model if it is reported in a scholarly publication or report.But, given the onerous costs involved, researchers often avoid preparing information-rich graphics and exploring several statistical approaches or tests available.The ggstatsplot package in the R programming language (R Core Team, 2021) provides a one-line syntax to enrich ggplot2based visualizations with the results from statistical analysis embedded in the visualization itself.In doing so, the package helps researchers adopt a rigorous, reliable, and robust data exploratory and reporting workflow."}23{"work_id": 3133457239, "title": "Numerical methods for topography simulation", "abstract": "Die Simulation von Herstellungsschritten in der Halbleiterfertigung erlaubt nicht nurein besseres Verst\u00e4ndnis der zugrunde liegenden Physik, sondern auch die Prozessop-timierung ohne teure Experimente. Viele Schritte in der Prozesskette, um integrierte Schaltungen herzustellen, ver\u00e4ndern die Topographie der Waferoberfl\u00e4che durch \u00c4tzenoder Abscheidung neuer Materialschichten. Diese Arbeit pr\u00e4sentiert neue numerische Verfahren, die eine effiziente und genaue Simulation solcher Prozesse erlauben. Ein Hauptproblem der Topographiesimulation stellt die korrekte zeitliche Beschreibung der geometrischen Ver\u00e4nderungen, insbesondere in drei Dimensionen, dar. Daher wurde basierend auf der Level-Set-Methode eine Technikentwickelt, die neueste Algorithmen und Datenstrukturen, wie die Sparse-Field-Methode oder hierarchische Laufl\u00e4ngenkodierung, benutzt, um Rechenzeit sowie Speicherverbrauch zu minimierenund die Zeitentwicklung gro\u00dfer dreidimensionaler Geometrien zu erm\u00f6glichen. Eine genaue Ber\u00fccksichtigung verschiedenener Materialschichten und derdavon abh\u00e4ngigen Oberfl\u00e4chenraten ist f\u00fcr \u00c4tzprozesse besonders wichtig und konnte mit einer neuartigen Multi-Level-Set-Methode erreicht werden. Zudem wurden Algorithmen f\u00fcr diversegeometrische Operationen und f\u00fcr den Test auf gerichtete Sichtbarkeit und Konnektivit\u00e4t verwirklicht. Um moderne Multikernprozessoren auszun\u00fctzen, wird ein neuer Ansatz f\u00fcr die Parallelisierung der hierarchischen Laufl\u00e4ngenkodierung pr\u00e4sentiert. Ein weiteres Problem ist die Bestimmung der Oberfl\u00e4chenraten f\u00fcr realistische Topo-graphiesimulationen. Erweiterte Modelle f\u00fcr die Beschreibung der Oberfl\u00e4chenkinetikerfordern die Kenntnis der Teilchenflussverteilung an der Oberfl\u00e4che. Obwohl meistensballistischer Teilchentransport angenommen werden kann,ist die Berechnung dennochsehr aufw \u0308andig, wenn Reemissionen oder spiegelartige Reflexionen ber\u00fccksichtigt werden sollen. Simulationen sind daher oft limitiert auf vereinfachte Modelle oder kleineStrukturen. Ein vielversprechender Ansatz, um diese Einschr\u00e4nkung zu \u00fcberwinden, ist eine Monte-Carlo-Methode, die durch die Simulation vieler Teilchentrajektoriendie Flussverteilung bestimmt. Diese Arbeit pr\u00e4sentiert ein neues Verfahren, das diese Monte-Carlo-Berechnung direkt auf die implizite Oberfl\u00e4chendarstellung der Level-Set-Methode anwendet. Zudem wurde der Rechenaufwand durchdie Anwendung vonerweiterten Raytracing-Algorithmen und -Datenstrukturen, die f\u00fcr die Bed\u00fcrfnisse von Topographiesimulationen adaptiert und optimiert wurden,reduziert. Schlussendlich werden die gezeigten numerischen Methodenanhand verschiedener inder Literatur beschriebene Prozessmodelle getestet, um die vielf\u00e4ltige Anwendbarkeit, insbesondere f\u00fcr gro\u00dfe dreidimensionale Strukturen, zu demonstrieren."}24{"work_id": 7140287209, "title": "Towards end-to-end automation of AI research", "abstract": "Abstract The automation of science is a long-standing ambition in artificial intelligence (AI) research 1,2 . Although the community has made substantial progress in automating individual components of the scientific process, a system that autonomously navigates the entire research life cycle\u2014from conception to publication\u2014has remained out of reach. Here we present a pipeline for automating the entire scientific process end to end. We present The AI Scientist, which creates research ideas, writes code, runs experiments, plots and analyses data, writes the entire scientific manuscript, and performs its own peer review. Its ideas, execution and presentation are of sufficient quality that the manuscript generated by this AI system passed the first round of peer review for a workshop of a top-tier machine learning conference. The workshop had an acceptance rate of 70%. Our system leverages modern foundation models 3\u20135 within a complex agentic system. We evaluate The AI Scientist in two settings: a focused mode using human-provided code templates as an initial scaffold for conducting research on a specific topic and a template-free, open-ended mode that leverages agentic search for wider scientific exploration 6,7 . Both settings produce diverse ideas and automatically test, report on and evaluate them. This achievement demonstrates the growing capacity of AI for making scientific contributions and signifies a potential paradigm shift in how research is conducted. As with any impactful new technology, there could be important risks, including taxing overwhelmed review systems and adding noise to the scientific literature. However, if developed responsibly, such autonomous systems could greatly accelerate scientific discovery."}25{"work_id": 3045710579, "title": "The ITensor Software Library for Tensor Network Calculations", "abstract": "ITensor is a system for programming tensor network calculations with an interface modeled on tensor diagrams, allowing users to focus on the connectivity of a tensor network without manually bookkeeping tensor indices. The ITensor interface rules out common programming errors and enables rapid prototyping of algorithms. After discussing the philosophy behind the ITensor approach, we show examples of each part of the interface including Index objects, the ITensor product operator, tensor factorizations, tensor storage types, algorithms for matrix product state (MPS) and matrix product operator (MPO) tensor networks, quantum number conserving block sparse tensors, and the NDTensors library. We also review publications that have used ITensor for quantum many-body physics and for other areas where tensor networks are increasingly applied. To conclude we discuss promising features and optimizations to be added in the future."}26{"work_id": 2769423117, "title": "\u201cFound in Translation\u201d: predicting outcomes of complex organic chemistry reactions using neural sequence-to-sequence models", "abstract": "There is an intuitive analogy of an organic chemist's understanding of a compound and a language speaker's understanding of a word. Based on this analogy, it is possible to introduce the basic concepts and analyze potential impacts of linguistic analysis to the world of organic chemistry. In this work, we cast the reaction prediction task as a translation problem by introducing a template-free sequence-to-sequence model, trained end-to-end and fully data-driven. We propose a tokenization, which is arbitrarily extensible with reaction information. Using an attention-based model borrowed from human language translation, we improve the state-of-the-art solutions in reaction prediction on the top-1 accuracy by achieving 80.3% without relying on auxiliary knowledge, such as reaction templates or explicit atomic features. Also, a top-1 accuracy of 65.4% is reached on a larger and noisier dataset."}27{"work_id": 3099929043, "title": "Bayesian probabilistic numerical methods", "abstract": "The increasing complexity of computer models used to solve contemporary inference problems has been set against a decreasing rate of improvement in processor speed in recent years. As a result, in many of these problems numerical error is a challenge for practitioners. However, while there has been a recent push towards rigorous quantification of uncertainty in inference problems based upon computer models, numerical error is still largely required to be driven down to a level at which its impact on inferences is negligible. Probabilistic numerical methods have been proposed to alleviate this; these are a class of numerical methods that return probabilistic uncertainty quantification for their numerical error. The attraction of such methods is clear: if numerical error in the computer model and uncertainty in an inference problem are quantified in a unified framework then careful tuning of numerical methods to mitigate the impact of numerical error on inferences could become unnecessary. \\n \\nIn this thesis we introduce the class of Bayesian probabilistic numerical methods, whose uncertainty has a strict and rigorous Bayesian interpretation. A number of examples of conjugate Bayesian probabilistic numerical methods are presented before we present analysis and algorithms for the general case, in which the posterior distribution does not posess a closed form. We conclude by studying how these methods can be rigorously composed to yield Bayesian pipelines of computation. Throughout we present applications of the developed methods to real-world inference problems, and indicate that the uncertainty quantification provided by these methods can be of significant practical use. \\n"}28{"work_id": 1494474111, "title": "7 Linear algebra applications", "abstract": "Linear algebra is the most widely studied branch of mathematics after calculus.There are good reasons for this as it plays an important role in many fields.The readership the authors had in mind for this book includes majors in disciplines such as mathematics, engineering and social sciences.It will be useful for beginners and also as a reference for graduates.It introduces linear algebra, but at the same time it is tersely written and includes a great deal of material, a good lot contained in the exercises which, however, also contain many numerical ones.The chapter headings are: (1) Numbers, vectors and fields, (2) Matrices, (3) Row operations, (4) Vector spaces, (5) Linear mappings, (6) Inner product spaces, (7) Similarity and determinants, (8) Characteristic polynomial and eigenvalues of a matrix, (9) Some applications, (10) Unitary, orthogonal, Hermitian and symmetric matrices, (11) The singular value decomposition, and an appendix on using Maple."}29{"work_id": 4396723768, "title": "Augmenting large language models with chemistry tools", "abstract": "Large language models (LLMs) have shown strong performance in tasks across domains but struggle with chemistry-related problems. These models also lack access to external knowledge sources, limiting their usefulness in scientific applications. We introduce ChemCrow, an LLM chemistry agent designed to accomplish tasks across organic synthesis, drug discovery and materials design. By integrating 18 expert-designed tools and using GPT-4 as the LLM, ChemCrow augments the LLM performance in chemistry, and new capabilities emerge. Our agent autonomously planned and executed the syntheses of an insect repellent and three organocatalysts and guided the discovery of a novel chromophore. Our evaluation, including both LLM and expert assessments, demonstrates ChemCrow's effectiveness in automating a diverse set of chemical tasks. Our work not only aids expert chemists and lowers barriers for non-experts but also fosters scientific advancement by bridging the gap between experimental and computational chemistry."}30{"work_id": 4403324307, "title": "Chai-1: Decoding the molecular interactions of life", "abstract": "Abstract We introduce Chai-1, a multi-modal foundation model for molecular structure prediction that performs at the state-of-the-art across a variety of tasks relevant to drug discovery. Chai-1 can optionally be prompted with experimental restraints (e.g. derived from wet-lab data) which boosts performance by double-digit percentage points. Chai-1 can also be run in single-sequence mode with-out MSAs while preserving most of its performance. We release Chai-1 model weights and inference code as a Python package for non-commercial use and via a web interface where it can be used for free including for commercial drug discovery purposes."}31{"work_id": 4407041525, "title": "AI-Driven Inverse Design of Materials: Past, Present, and Future", "abstract": "Abstract The discovery of advanced materials is a cornerstone of human technological development and progress. The structures of materials and their corresponding properties are essentially the result of a complex interplay of multiple degrees of freedom such as lattice, charge, spin, symmetry, and topology. This poses significant challenges for the inverse design methods of materials. Humans have long explored new materials through numerous experiments and proposed corresponding theoretical systems to predict new material properties and structures. With the improvement of computational power, researchers have gradually developed various electronic-structure calculation methods, such as the density functional theory and high-throughput computational methods. Recently, the rapid development of artificial intelligence (AI) technology in computer science has enabled the effective characterization of the implicit association between material properties and structures, thus forming an efficient paradigm for the inverse design of functional materials. Significant progress has been achieved in the inverse design of materials based on generative and discriminative models, attracting widespread interest from researchers. Considering this rapid technological progress, in this survey, we examine the latest advancements in AI-driven inverse design of materials by introducing the background, key findings, and mainstream technological development routes. In addition, we summarize the remaining challenges for future directions. This survey provides the latest overview of AI-driven inverse design of materials, which can serve as a useful resource for researchers."}32{"work_id": 2913606428, "title": "PsychoPy2: Experiments in behavior made easy", "abstract": "PsychoPy is an application for the creation of experiments in behavioral science (psychology, neuroscience, linguistics, etc.) with precise spatial control and timing of stimuli. It now provides a choice of interface; users can write scripts in Python if they choose, while those who prefer to construct experiments graphically can use the new Builder interface. Here we describe the features that have been added over the last 10 years of its development. The most notable addition has been that Builder interface, allowing users to create studies with minimal or no programming, while also allowing the insertion of Python code for maximal flexibility. We also present some of the other new features, including further stimulus options, asynchronous time-stamped hardware polling, and better support for open science and reproducibility. Tens of thousands of users now launch PsychoPy every month, and more than 90 people have contributed to the code. We discuss the current state of the project, as well as plans for the future."}33{"work_id": 2899760200, "title": "The PRIDE database and related tools and resources in 2019: improving support for quantification data", "abstract": "The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world's largest data repository of mass spectrometry-based proteomics data, and is one of the founding members of the global ProteomeXchange (PX) consortium. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2016. In the last 3 years, public data sharing through PRIDE (as part of PX) has definitely become the norm in the field. In parallel, data re-use of public proteomics data has increased enormously, with multiple applications. We first describe the new architecture of PRIDE Archive, the archival component of PRIDE. PRIDE Archive and the related data submission framework have been further developed to support the increase in submitted data volumes and additional data types. A new scalable and fault tolerant storage backend, Application Programming Interface and web interface have been implemented, as a part of an ongoing process. Additionally, we emphasize the improved support for quantitative proteomics data through the mzTab format. At last, we outline key statistics on the current data contents and volume of downloads, and how PRIDE data are starting to be disseminated to added-value resources including Ensembl, UniProt and Expression Atlas."}34{"work_id": 3208691473, "title": "The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences", "abstract": "The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world's largest data repository of mass spectrometry-based proteomics data. PRIDE is one of the founding members of the global ProteomeXchange (PX) consortium and an ELIXIR core data resource. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2019. The number of submitted datasets to PRIDE Archive (the archival component of PRIDE) has reached on average around 500 datasets per month during 2021. In addition to continuous improvements in PRIDE Archive data pipelines and infrastructure, the PRIDE Spectra Archive has been developed to provide direct access to the submitted mass spectra using Universal Spectrum Identifiers. As a key point, the file format MAGE-TAB for proteomics has been developed to enable the improvement of sample metadata annotation. Additionally, the resource PRIDE Peptidome provides access to aggregated peptide/protein evidences across PRIDE Archive. Furthermore, we will describe how PRIDE has increased its efforts to reuse and disseminate high-quality proteomics data into other added-value resources such as UniProt, Ensembl and Expression Atlas."}35{"work_id": 4395010444, "title": "ProTox 3.0: a webserver for the prediction of toxicity of chemicals", "abstract": "Interaction with chemicals, present in drugs, food, environments, and consumer goods, is an integral part of our everyday life. However, depending on the amount and duration, such interactions can also result in adverse effects. With the increase in computational methods, the in silico methods can offer significant benefits to both regulatory needs and requirements for risk assessments and the pharmaceutical industry to assess the safety profile of a chemical. Here, we present ProTox 3.0, which incorporates molecular similarity and machine-learning models for the prediction of 61 toxicity endpoints such as acute toxicity, organ toxicity, clinical toxicity, molecular-initiating events (MOE), adverse outcomes (Tox21) pathways, several other toxicological endpoints and toxicity off-targets. All the ProTox 3.0 models are validated on independent external sets and have shown strong performance. ProTox envisages itself as a complete, freely available computational platform for in silico toxicity prediction for toxicologists, regulatory agencies, computational chemists, and medicinal chemists. The ProTox 3.0 webserver is free and open to all users, and there is no login requirement and can be accessed via https://tox.charite.de. The web server takes a 2D chemical structure as input and reports the toxicological profile of the compound for each endpoint with a confidence score and overall toxicity radar plot and network plot."}36{"work_id": 2766160192, "title": "Advanced Bayesian Multilevel Modeling with the R Package brms", "abstract": "The brms package allows R users to easily specify a wide range of Bayesian single-level and multilevel models, which are fitted with the probabilistic programming language Stan behind the scenes. Several response distributions are supported, of which all parameters (e.g., location, scale, and shape) can be predicted at the same time thus allowing for distributional regression. Non-linear relationships may be specified using non-linear predictor terms or semi-parametric approaches such as splines or Gaussian processes. To make all of these modeling options possible in a multilevel framework, brms provides an intuitive and powerful formula syntax, which extends the well known formula syntax of lme4. The purpose of the present paper is to introduce this syntax in detail and to demonstrate its usefulness with four examples, each showing other relevant aspects of the syntax."}37{"work_id": 4393936599, "title": "ADMETlab 3.0: an updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support", "abstract": "ADMETlab 3.0 is the second updated version of the web server that provides a comprehensive and efficient platform for evaluating ADMET-related parameters as well as physicochemical properties and medicinal chemistry characteristics involved in the drug discovery process. This new release addresses the limitations of the previous version and offers broader coverage, improved performance, API functionality, and decision support. For supporting data and endpoints, this version includes 119 features, an increase of 31 compared to the previous version. The updated number of entries is 1.5 times larger than the previous version with over 400 000 entries. ADMETlab 3.0 incorporates a multi-task DMPNN architecture coupled with molecular descriptors, a method that not only guaranteed calculation speed for each endpoint simultaneously, but also achieved a superior performance in terms of accuracy and robustness. In addition, an API has been introduced to meet the growing demand for programmatic access to large amounts of data in ADMETlab 3.0. Moreover, this version includes uncertainty estimates in the prediction results, aiding in the confident selection of candidate compounds for further studies and experiments. ADMETlab 3.0 is publicly for access without the need for registration at: https://admetlab3.scbdd.com."}38{"work_id": 2990427812, "title": "Welcome to the Tidyverse", "abstract": "At a high level, the tidyverse is a language for solving data science challenges with R code.Its primary goal is to facilitate a conversation between a human and a computer about data.Less abstractly, the tidyverse is a collection of R packages that share a high-level design philosophy and low-level grammar and data structures, so that learning one package makes it easier to learn the next."}39{"work_id": 4400581728, "title": "An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013\u20132023)", "abstract": "This Perspective is a continuation of our analysis of U.S. FDA-approved small-molecule drugs (1938\u20132012) containing nitrogen heterocycles. In this study we report drug structure and property analyses of 321 unique new small-molecule drugs approved from January 2013 to December 2023 as well as information about frequency of important heteroatoms such as sulfur and fluorine and key small nitrogen substituents (CN and NO 2 ). The most notable change is an incredible increase in drugs containing at least one nitrogen heterocycle\u250082%, compared to 59% from preceding decades\u2500as well as a significant increase in the number of nitrogen heterocycles per drug. Pyridine has claimed the #1 high-frequency nitrogen heterocycle occurrence spot from piperidine (#2), with pyrimidine (#5), pyrazole (#6), and morpholine (#9) being the big top 10 climbers. Also notable is high number of fused nitrogen heterocycles, apparently driven largely by newly approved cancer drugs."}40{"work_id": 7119529911, "title": "Deep contrastive learning enables genome-wide virtual screening", "abstract": "Abstract Numerous protein-coding genes are associated with human diseases, yet approximately 90% of them lack targeted therapeutic intervention. While conventional computational methods, such as molecular docking, have facilitated the discovery of potential hit compounds, the development of genome-wide virtual screening against the expansive chemical space remains a formidable challenge. Here we introduce DrugCLIP, a novel framework that combines contrastive learning and dense retrieval to achieve rapid and accurate virtual screening. Compared to traditional docking methods, DrugCLIP improves the speed of virtual screening by up to seven orders of magnitude. In terms of performance, DrugCLIP not only surpasses docking and other deep learning-based methods across two standard benchmark datasets, but also demonstrates high efficacy in wet-lab experiments. Specifically, DrugCLIP successfully identified agonists with < 100 nM affinities for 5HT 2A R, a key target in psychiatric diseases. For another target NET, whose structure is newly solved and not included in the training set, our method achieved a hit rate of 15%, with 12 diverse molecules exhibiting affinities better than bupropion. Additionally, two chemically novel inhibitors were validated by structure determination with Cryo-EM. Finally, a novel potential drug target TRIP12, with no experimental structures and inhibitors for reference, was used to challenge DrugCLIP. DrugCLIP achieved a hit rate of 17.5% by screening a pocket identified on an AlphaFold2-predicted structure, verified with multi-cycle SPR assays. Molecules with the highest affinities also showed a dose-dependent inhibition to the enzymatic function of TRIP12. Building on this foundation, we present the results of a pioneering trillion-scale genome-wide virtual screening, encompassing approximately 10,000 AlphaFold2 predicted proteins within the human genome and 500 million molecules from the ZINC and Enamine REAL database. This work provides an innovative perspective on drug discovery in the post-AlphaFold era, where comprehensive targeting of all disease-related proteins is within reach."}41{"work_id": 4391561379, "title": "Leveraging large language models for predictive chemistry", "abstract": "Abstract Machine learning has transformed many fields and has recently found applications in chemistry and materials science. The small datasets commonly found in chemistry sparked the development of sophisticated machine learning approaches that incorporate chemical knowledge for each application and, therefore, require specialized expertise to develop. Here we show that GPT-3, a large language model trained on vast amounts of text extracted from the Internet, can easily be adapted to solve various tasks in chemistry and materials science by fine-tuning it to answer chemical questions in natural language with the correct answer. We compared this approach with dedicated machine learning models for many applications spanning the properties of molecules and materials to the yield of chemical reactions. Surprisingly, our fine-tuned version of GPT-3 can perform comparably to or even outperform conventional machine learning techniques, in particular in the low-data limit. In addition, we can perform inverse design by simply inverting the questions. The ease of use and high performance, especially for small datasets, can impact the fundamental approach to using machine learning in the chemical and material sciences. In addition to a literature search, querying a pre-trained large language model might become a routine way to bootstrap a project by leveraging the collective knowledge encoded in these foundation models, or to provide a baseline for predictive tasks."}42{"work_id": 4302307901, "title": "DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking", "abstract": "Predicting the binding structure of a small molecule ligand to a protein -- a task known as molecular docking -- is critical to drug design. Recent deep learning methods that treat docking as a regression problem have decreased runtime compared to traditional search-based methods but have yet to offer substantial improvements in accuracy. We instead frame molecular docking as a generative modeling problem and develop DiffDock, a diffusion generative model over the non-Euclidean manifold of ligand poses. To do so, we map this manifold to the product space of the degrees of freedom (translational, rotational, and torsional) involved in docking and develop an efficient diffusion process on this space. Empirically, DiffDock obtains a 38% top-1 success rate (RMSD<2A) on PDBBind, significantly outperforming the previous state-of-the-art of traditional docking (23%) and deep learning (20%) methods. Moreover, while previous methods are not able to dock on computationally folded structures (maximum accuracy 10.4%), DiffDock maintains significantly higher precision (21.7%). Finally, DiffDock has fast inference times and provides confidence estimates with high selective accuracy."}43{"work_id": 4241803778, "title": "PETSc Users Manual (Rev. 3.13)", "abstract": "This manual describes the use of PETSc for the numerical solution of partial differential equations and related problems on high-performance computers. The Portable, Extensible Toolkit for Scientific Computation (PETSc) is a suite of data structures and routines that provide the building blocks for the implementation of large-scale application codes on parallel (and serial) computers. PETSc uses the MPI standard for all message-passing communication. PETSc includes an expanding suite of parallel linear solvers, nonlinear solvers, and time integrators that may be used in application codes written in Fortran, C, C++, and Python. PETSc provides many of the mechanisms needed within parallel application codes, such as parallel matrix and vector assembly routines. The library is organized hierarchically, enabling users to employ the level of abstraction that is most appropriate for a particular problem. By using techniques of object-oriented programming, PETSc provides enormous flexibility for users. PETSc is a sophisticated set of software tools; as such, for some users it initially has a much steeper learning curve than a simple subroutine library. In particular, for individuals without some computer science background, experience programming in C, C++, python, or Fortran and experience using a debugger such as gdb or dbx, it may require a significant amount of time to take full advantage of the features that enable efficient software use. However, the power of the PETSc design and the algorithms it incorporates may make the efficient implementation of many application codes simpler than \\rolling them\" yourself."}44{"work_id": 4365512576, "title": "ChatGPT: A comprehensive review on background, applications, key challenges, bias, ethics, limitations and future scope", "abstract": "In recent years, artificial intelligence (AI) and machine learning have been transforming the landscape of scientific research. Out of which, the chatbot technology has experienced tremendous advancements in recent years, especially with ChatGPT emerging as a notable AI language model. This comprehensive review delves into the background, applications, key challenges, and future directions of ChatGPT. We begin by exploring its origins, development, and underlying technology, before examining its wide-ranging applications across industries such as customer service, healthcare, and education. We also highlight the critical challenges that ChatGPT faces, including ethical concerns, data biases, and safety issues, while discussing potential mitigation strategies. Finally, we envision the future of ChatGPT by exploring areas of further research and development, focusing on its integration with other technologies, improved human-AI interaction, and addressing the digital divide. This review offers valuable insights for researchers, developers, and stakeholders interested in the ever-evolving landscape of AI-driven conversational agents. This study explores the various ways ChatGPT has been revolutionizing scientific research, spanning from data processing and hypothesis generation to collaboration and public outreach. Furthermore, the paper examines the potential challenges and ethical concerns surrounding the use of ChatGPT in research, while highlighting the importance of striking a balance between AI-assisted innovation and human expertise. The paper presents several ethical issues in existing computing domain and how ChatGPT can invoke challenges to such notion. This work also includes some biases and limitations of ChatGPT. It is worth to note that despite of several controversies and ethical concerns, ChatGPT has attracted remarkable attentions from academia, research, and industries in a very short span of time."}45{"work_id": 3097145107, "title": "PubChem in 2021: new data content and improved web interfaces", "abstract": "PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)."}46{"work_id": 4389991792, "title": "Autonomous chemical research with large language models", "abstract": "Abstract Transformer-based large language models are making significant strides in various fields, such as natural language processing 1\u20135 , biology 6,7 , chemistry 8\u201310 and computer programming 11,12 . Here, we show the development and capabilities of Coscientist, an artificial intelligence system driven by GPT-4 that autonomously designs, plans and performs complex experiments by incorporating large language models empowered by tools such as internet and documentation search, code execution and experimental automation. Coscientist showcases its potential for accelerating research across six diverse tasks, including the successful reaction optimization of palladium-catalysed cross-couplings, while exhibiting advanced capabilities for (semi-)autonomous experimental design and execution. Our findings demonstrate the versatility, efficacy and explainability of artificial intelligence systems like Coscientist in advancing research."}47{"work_id": 3168436232, "title": "AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings", "abstract": "AutoDock Vina is arguably one of the fastest and most widely used open-source programs for molecular docking. However, compared to other programs in the AutoDock Suite, it lacks support for modeling specific features such as macrocycles or explicit water molecules. Here, we describe the implementation of this functionality in AutoDock Vina 1.2.0. Additionally, AutoDock Vina 1.2.0 supports the AutoDock4.2 scoring function, simultaneous docking of multiple ligands, and a batch mode for docking a large number of ligands. Furthermore, we implemented Python bindings to facilitate scripting and the development of docking workflows. This work is an effort toward the unification of the features of the AutoDock4 and AutoDock Vina programs. The source code is available at https://github.com/ccsb-scripps/AutoDock-Vina."}48{"work_id": 3010959735, "title": "Gaussin prosessi -surrogaattimenetelmi\u00e4 likim\u00e4\u00e4r\u00e4iseen Bayesilaiseen p\u00e4\u00e4ttelyyn", "abstract": "In many application fields such as ecology, epidemiology and astronomy, simulation models are used to study complex phenomena that occur in nature. Often the analytical form of the likelihood function of these models is either unavailable or too costly to evaluate which complicates statistical inference. Likelihood-free inference (LFI) methods such as approximate Bayesian computation (ABC), based on replacing the evaluations of the intractable likelihood with forward simulations of the model, have become a popular approach to conduct inference for simulation models. Nevertheless, current LFI methods feature several computational and statistical challenges. Especially, standard ABC algorithms require a huge number of simulations which makes them infeasible when the forward simulations are expensive. This thesis deals with likelihood-free inference for computationally costly models. The main contribution is a coherent framework for LFI based on Gaussian process (GP) surrogate models. GP models allow to encode smoothness assumptions of the simulation model output to reduce the amount of simulations needed. Additionally, the uncertainty in the resulting model-based posterior approximations due to the limited simulation budget can be quantified. We develop Bayesian experimental design strategies to select the evaluation locations as to minimise the computational cost. Both sequential designs, where simulations are chosen one-at-a-time basis, and batch strategies, which allow to take advantage of parallel computing, are derived. In addition to the LFI scenario, the proposed methods also apply when the likelihood can be evaluated but is expensive. In essence, the proposed framework can be viewed as an LFI counterpart of probabilistic numerical methods such as Bayesian optimisation, developed for optimising expensive objective functions, and Bayesian quadrature, developed for computing integrals of expensive functions. We demonstrate the advantages of the proposed LFI methods using extensive empirical simulations. Some theoretical analysis of the proposed algorithms is also provided and their relation to some other GP surrogate methods are discussed. In addition to the contributions to statistical methodology, applications in population genomics are also considered. In particular, we use the GP-based ABC methodology to obtain an approximate posterior of a simulation model describing horizontal gene transfer in bacteria. We also develop a probabilistic model and an inference algorithm using a novel combination of ABC and Metropolis-within-Gibbs sampling to facilitate better understanding of bacterial colonisation."}49{"work_id": 4388615774, "title": "DrugBank 6.0: the DrugBank Knowledgebase for 2024", "abstract": "First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists."}50{"work_id": 4225106311, "title": "FAIR data enabling new horizons for materials research", "abstract": "The prosperity and lifestyle of our society are very much governed by achievements in condensed matter physics, chemistry and materials science, because new products for sectors such as energy, the environment, health, mobility and information technology (IT) rely largely on improved or even new materials. Examples include solid-state lighting, touchscreens, batteries, implants, drug delivery and many more. The enormous amount of research data produced every day in these fields represents a gold mine of the twenty-first century. This gold mine is, however, of little value if these data are not comprehensively characterized and made available. How can we refine this feedstock; that is, turn data into knowledge and value? For this, a FAIR (findable, accessible, interoperable and reusable) data infrastructure is a must. Only then can data be readily shared and explored using data analytics and artificial intelligence (AI) methods. Making data 'findable and AI ready' (a forward-looking interpretation of the acronym) will change the way in which science is carried out today. In this Perspective, we discuss how we can prepare to make this happen for the field of materials science."}51{"work_id": 4200153169, "title": "Variational and Quasi-Variational Inequalities", "abstract": "This chapter presents a concise introduction to the theory of variational and quasi-variational inequalities. The available literature on these topics is vast, and we only give the most fundamental results which have direct relevance to our study of variational inequalities with random data. The presented material, which we will frequently use in the forthcoming chapters, can be divided into three parts. The first part deals with linear variational inequalities given by bilinear forms. In this setting, we provide an equivalent optimization formulation of the variational inequality under a symmetry condition on the bilinear form. We provide the so-called Minty variational inequality, study the solution set&s;s structure, and give some existence results. Focusing on elliptic regularization, we examine the behavior of the regularized solutions and relate it to the solvability of variational inequalities. We then study non-coercive variational inequalities and, under appropriate conditions, give some sufficient conditions for the existence of a solution. The second part deals with nonlinear variational inequalities involving some classes of nonlinear operators. We present existence results by using arguments based on the projection map. We develop a regularization framework by focusing on the case when the constraint sets are perturbed and provide a rate of convergence for the regularized solutions. We also briefly discuss penalization and use it to give some existence results for nonlinear variational inequalities in Banach spaces. In the third part, we then deal with quasi-variational inequalities. We present existence results for general constraint sets as well as by exploiting a particular structure of the constraint set. The chapter concludes with a discussion of some of the related contributions."}52{"work_id": 3003257820, "title": "SciPy 1.0: fundamental algorithms for scientific computing in Python", "abstract": "SciPy is an open-source scientific computing library for the Python programming language. Since its initial release in 2001, SciPy has become a de facto standard for leveraging scientific algorithms in Python, with over 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories and millions of downloads per year. In this work, we provide an overview of the capabilities and development practices of SciPy 1.0 and highlight some recent technical developments."}53{"work_id": 2804822363, "title": "SWISS-MODEL: homology modelling of protein structures and complexes", "abstract": "Homology modelling has matured into an important technique in structural biology, significantly contributing to narrowing the gap between known protein sequences and experimentally determined structures. Fully automated workflows and servers simplify and streamline the homology modelling process, also allowing users without a specific computational expertise to generate reliable protein models and have easy access to modelling results, their visualization and interpretation. Here, we present an update to the SWISS-MODEL server, which pioneered the field of automated modelling 25 years ago and been continuously further developed. Recently, its functionality has been extended to the modelling of homo- and heteromeric complexes. Starting from the amino acid sequences of the interacting proteins, both the stoichiometry and the overall structure of the complex are inferred by homology modelling. Other major improvements include the implementation of a new modelling engine, ProMod3 and the introduction a new local model quality estimation method, QMEANDisCo. SWISS-MODEL is freely available at https://swissmodel.expasy.org."}54{"work_id": 3156458251, "title": "Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation", "abstract": "The Interactive Tree Of Life (https://itol.embl.de) is an online tool for the display, manipulation and annotation of phylogenetic and other trees. It is freely available and open to everyone. iTOL version 5 introduces a completely new tree display engine, together with numerous new features. For example, a new dataset type has been added (MEME motifs), while annotation options have been expanded for several existing ones. Node metadata display options have been extended and now also support non-numerical categorical values, as well as multiple values per node. Direct manual annotation is now available, providing a set of basic drawing and labeling tools, allowing users to draw shapes, labels and other features by hand directly onto the trees. Support for tree and dataset scales has been extended, providing fine control over line and label styles. Unrooted tree displays can now use the equal-daylight algorithm, proving a much greater display clarity. The user account system has been streamlined and expanded with new navigation options and currently handles >1 million trees from >70 000 individual users."}55{"work_id": 4223552703, "title": "Search and sequence analysis tools services from EMBL-EBI in 2022", "abstract": "The EMBL-EBI search and sequence analysis tools frameworks provide integrated access to EMBL-EBI's data resources and core bioinformatics analytical tools. EBI Search (https://www.ebi.ac.uk/ebisearch) provides a full-text search engine across nearly 5 billion entries, while the Job Dispatcher tools framework (https://www.ebi.ac.uk/services) enables the scientific community to perform a diverse range of sequence analysis using popular bioinformatics applications. Both allow users to interact through user-friendly web applications, as well as via RESTful and SOAP-based APIs. Here, we describe recent improvements to these services and updates made to accommodate the increasing data requirements during the COVID-19 pandemic."}56{"work_id": 3027286012, "title": "TIMER2.0 for analysis of tumor-infiltrating immune cells", "abstract": "Tumor progression and the efficacy of immunotherapy are strongly influenced by the composition and abundance of immune cells in the tumor microenvironment. Due to the limitations of direct measurement methods, computational algorithms are often used to infer immune cell composition from bulk tumor transcriptome profiles. These estimated tumor immune infiltrate populations have been associated with genomic and transcriptomic changes in the tumors, providing insight into tumor-immune interactions. However, such investigations on large-scale public data remain challenging. To lower the barriers for the analysis of complex tumor-immune interactions, we significantly improved our previous web platform TIMER. Instead of just using one algorithm, TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation of immune infiltration levels for The Cancer Genome Atlas (TCGA) or user-provided tumor profiles using six state-of-the-art algorithms. TIMER2.0 provides four modules for investigating the associations between immune infiltrates and genetic or clinical features, and four modules for exploring cancer-related associations in the TCGA cohorts. Each module can generate a functional heatmap table, enabling the user to easily identify significant associations in multiple cancer types simultaneously. Overall, the TIMER2.0 web server provides comprehensive analysis and visualization functions of tumor infiltrating immune cells."}57{"work_id": 3136918052, "title": "UniProt: a worldwide hub of protein knowledge", "abstract": "The UniProt Knowledgebase is a collection of sequences and annotations for over 120 million proteins across all branches of life. Detailed annotations extracted from the literature by expert curators have been collected for over half a million of these proteins. These annotations are supplemented by annotations provided by rule based automated systems, and those imported from other resources. In this article we describe significant updates that we have made over the last 2 years to the resource. We have greatly expanded the number of Reference Proteomes that we provide and in particular we have focussed on improving the number of viral Reference Proteomes. The UniProt website has been augmented with new data visualizations for the subcellular localization of proteins as well as their structure and interactions. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/."}58{"work_id": 3107527779, "title": "The STRING database in 2021: customizable protein\u2013protein networks, and functional characterization of user-uploaded gene/measurement sets", "abstract": "Cellular life depends on a complex web of functional associations between biomolecules. Among these associations, protein-protein interactions are particularly important due to their versatility, specificity and adaptability. The STRING database aims to integrate all known and predicted associations between proteins, including both physical interactions as well as functional associations. To achieve this, STRING collects and scores evidence from a number of sources: (i) automated text mining of the scientific literature, (ii) databases of interaction experiments and annotated complexes/pathways, (iii) computational interaction predictions from co-expression and from conserved genomic context and (iv) systematic transfers of interaction evidence from one organism to another. STRING aims for wide coverage; the upcoming version 11.5 of the resource will contain more than 14 000 organisms. In this update paper, we describe changes to the text-mining system, a new scoring-mode for physical interactions, as well as extensive user interface features for customizing, extending and sharing protein networks. In addition, we describe how to query STRING with genome-wide, experimental data, including the automated detection of enriched functionalities and potential biases in the user's query data. The STRING resource is available online, at https://string-db.org/."}59{"work_id": 4409229284, "title": "CoverM: read alignment statistics for metagenomics", "abstract": "SUMMARY: Genome-centric analysis of metagenomic samples is a powerful method for understanding the function of microbial communities. Calculating read coverage is a central part of analysis, enabling differential coverage binning for recovery of genomes and estimation of microbial community composition. Coverage is determined by processing read alignments to reference sequences of either contigs or genomes. Per-reference coverage is typically calculated in an ad-hoc manner, with each software package providing its own implementation and specific definition of coverage. Here we present a unified software package CoverM which calculates several coverage statistics for contigs and genomes in an ergonomic and flexible manner. It uses \"Mosdepth arrays\" for computational efficiency and avoids unnecessary I/O overhead by calculating coverage statistics from streamed read alignment results. AVAILABILITY AND IMPLEMENTATION: CoverM is free software available at https://github.com/wwood/coverm. CoverM is implemented in Rust, with Python (https://github.com/apcamargo/pycoverm) and Julia (https://github.com/JuliaBinaryWrappers/CoverM_jll.jl) interfaces."}60{"work_id": 4383218913, "title": "Accurate medium-range global weather forecasting with 3D neural networks", "abstract": "Abstract Weather forecasting is important for science and society. At present, the most accurate forecast system is the numerical weather prediction (NWP) method, which represents atmospheric states as discretized grids and numerically solves partial differential equations that describe the transition between those states 1 . However, this procedure is computationally expensive. Recently, artificial-intelligence-based methods 2 have shown potential in accelerating weather forecasting by orders of magnitude, but the forecast accuracy is still significantly lower than that of NWP methods. Here we introduce an artificial-intelligence-based method for accurate, medium-range global weather forecasting. We show that three-dimensional deep networks equipped with Earth-specific priors are effective at dealing with complex patterns in weather data, and that a hierarchical temporal aggregation strategy reduces accumulation errors in medium-range forecasting. Trained on 39 years of global data, our program, Pangu-Weather, obtains stronger deterministic forecast results on reanalysis data in all tested variables when compared with the world\u2019s best NWP system, the operational integrated forecasting system of the European Centre for Medium-Range Weather Forecasts (ECMWF) 3 . Our method also works well with extreme weather forecasts and ensemble forecasts. When initialized with reanalysis data, the accuracy of tracking tropical cyclones is also higher than that of ECMWF-HRES."}61{"work_id": 4307425304, "title": "KEGG for taxonomy-based analysis of pathways and genomes", "abstract": "KEGG (https://www.kegg.jp) is a manually curated database resource integrating various biological objects categorized into systems, genomic, chemical and health information. Each object (database entry) is identified by the KEGG identifier (kid), which generally takes the form of a prefix followed by a five-digit number, and can be retrieved by appending /entry/kid in the URL. The KEGG pathway map viewer, the Brite hierarchy viewer and the newly released KEGG genome browser can be launched by appending /pathway/kid, /brite/kid and /genome/kid, respectively, in the URL. Together with an improved annotation procedure for KO (KEGG Orthology) assignment, an increasing number of eukaryotic genomes have been included in KEGG for better representation of organisms in the taxonomic tree. Multiple taxonomy files are generated for classification of KEGG organisms and viruses, and the Brite hierarchy viewer is used for taxonomy mapping, a variant of Brite mapping in the new KEGG Mapper suite. The taxonomy mapping enables analysis of, for example, how functional links of genes in the pathway and physical links of genes on the chromosome are conserved among organism groups."}62{"work_id": 4407002549, "title": "Benefits, limits, and risks of ChatGPT in medicine", "abstract": "ChatGPT represents a transformative technology in healthcare, with demonstrated impacts across clinical practice, medical education, and research. Studies show significant efficiency gains, including 70% reduction in administrative time for discharge summaries and achievement of medical professional-level performance on standardized tests (60% accuracy on USMLE, 78.2% on PubMedQA). ChatGPT offers personalized learning platforms, automated scoring, and instant access to vast medical knowledge in medical education, addressing resource limitations and enhancing training efficiency. It streamlines clinical workflows by supporting triage processes, generating discharge summaries, and alleviating administrative burdens, allowing healthcare professionals to focus more on patient care. Additionally, ChatGPT facilitates remote monitoring and chronic disease management, providing personalized advice, medication reminders, and emotional support, thus bridging gaps between clinical visits. Its ability to process and synthesize vast amounts of data accelerates research workflows, aiding in literature reviews, hypothesis generation, and clinical trial designs. This paper aims to gather and analyze published studies involving ChatGPT, focusing on exploring its advantages and disadvantages within the healthcare context. To aid in understanding and progress, our analysis is organized into six key areas: (1) Information and Education, (2) Triage and Symptom Assessment, (3) Remote Monitoring and Support, (4) Mental Healthcare Assistance, (5) Research and Decision Support, and (6) Language Translation. Realizing ChatGPT's full potential in healthcare requires addressing key limitations, such as its lack of clinical experience, inability to process visual data, and absence of emotional intelligence. Ethical, privacy, and regulatory challenges further complicate its integration. Future improvements should focus on enhancing accuracy, developing multimodal AI models, improving empathy through sentiment analysis, and safeguarding against artificial hallucination. While not a replacement for healthcare professionals, ChatGPT can serve as a powerful assistant, augmenting their expertise to improve efficiency, accessibility, and quality of care. This collaboration ensures responsible adoption of AI in transforming healthcare delivery. While ChatGPT demonstrates significant potential in healthcare transformation, systematic evaluation of its implementation across different healthcare settings reveals varying levels of evidence quality-from robust randomized trials in medical education to preliminary observational studies in clinical practice. This heterogeneity in evidence quality necessitates a structured approach to future research and implementation."}63{"work_id": 3096828292, "title": "KEGG: integrating viruses and cellular organisms", "abstract": "KEGG (https://www.kegg.jp/) is a manually curated resource integrating eighteen databases categorized into systems, genomic, chemical and health information. It also provides KEGG mapping tools, which enable understanding of cellular and organism-level functions from genome sequences and other molecular datasets. KEGG mapping is a predictive method of reconstructing molecular network systems from molecular building blocks based on the concept of functional orthologs. Since the introduction of the KEGG NETWORK database, various diseases have been associated with network variants, which are perturbed molecular networks caused by human gene variants, viruses, other pathogens and environmental factors. The network variation maps are created as aligned sets of related networks showing, for example, how different viruses inhibit or activate specific cellular signaling pathways. The KEGG pathway maps are now integrated with network variation maps in the NETWORK database, as well as with conserved functional units of KEGG modules and reaction modules in the MODULE database. The KO database for functional orthologs continues to be improved and virus KOs are being expanded for better understanding of virus-cell interactions and for enabling prediction of viral perturbations."}64{"work_id": 3095583226, "title": "Pfam: The protein families database in 2021", "abstract": "The Pfam database is a widely used resource for classifying protein sequences into families and domains. Since Pfam was last described in this journal, over 350 new families have been added in Pfam 33.1 and numerous improvements have been made to existing entries. To facilitate research on COVID-19, we have revised the Pfam entries that cover the SARS-CoV-2 proteome, and built new entries for regions that were not covered by Pfam. We have reintroduced Pfam-B which provides an automatically generated supplement to Pfam and contains 136 730 novel clusters of sequences that are not yet matched by a Pfam family. The new Pfam-B is based on a clustering by the MMseqs2 software. We have compared all of the regions in the RepeatsDB to those in Pfam and have started to use the results to build and refine Pfam repeat families. Pfam is freely available for browsing and download at http://pfam.xfam.org/."}65{"work_id": 4414990951, "title": "The rise of generative AI for metal-organic framework design and synthesis", "abstract": "Advances in generative artificial intelligence are transforming how metal-organic frameworks (MOFs) are designed and discovered. This perspective introduces the shift from laborious enumeration of MOF candidates to generative approaches that can autonomously propose and synthesize in the laboratory new porous reticular structures on demand. We outline the progress of employing deep learning models, such as variational autoencoders, diffusion models, and large language-model-based agents, that are fueled by the growing amount of available data from the MOF community and suggest novel crystalline materials designs. These generative tools can be combined with high-throughput computational screening and even automated experiments to form accelerated, closed-loop discovery pipelines. The result is a new paradigm for reticular chemistry in which AI algorithms more efficiently direct the search for high-performance MOF materials for clean air and energy applications. Finally, we highlight remaining challenges such as synthetic feasibility, dataset diversity, and the need for further integration of domain knowledge."}66{"work_id": 4308834893, "title": "The STRING database in 2023: protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest", "abstract": "Much of the complexity within cells arises from functional and regulatory interactions among proteins. The core of these interactions is increasingly known, but novel interactions continue to be discovered, and the information remains scattered across different database resources, experimental modalities and levels of mechanistic detail. The STRING database (https://string-db.org/) systematically collects and integrates protein-protein interactions-both physical interactions as well as functional associations. The data originate from a number of sources: automated text mining of the scientific literature, computational interaction predictions from co-expression, conserved genomic context, databases of interaction experiments and known complexes/pathways from curated sources. All of these interactions are critically assessed, scored, and subsequently automatically transferred to less well-studied organisms using hierarchical orthology information. The data can be accessed via the website, but also programmatically and via bulk downloads. The most recent developments in STRING (version 12.0) are: (i) it is now possible to create, browse and analyze a full interaction network for any novel genome of interest, by submitting its complement of encoded proteins, (ii) the co-expression channel now uses variational auto-encoders to predict interactions, and it covers two new sources, single-cell RNA-seq and experimental proteomics data and (iii) the confidence in each experimentally derived interaction is now estimated based on the detection method used, and communicated to the user in the web-interface. Furthermore, STRING continues to enhance its facilities for functional enrichment analysis, which are now fully available also for user-submitted genomes."}67{"work_id": 2898402099, "title": "The Pfam protein families database in 2019", "abstract": "The last few years have witnessed significant changes in Pfam (https://pfam.xfam.org). The number of families has grown substantially to a total of 17,929 in release 32.0. New additions have been coupled with efforts to improve existing families, including refinement of domain boundaries, their classification into Pfam clans, as well as their functional annotation. We recently began to collaborate with the RepeatsDB resource to improve the definition of tandem repeat families within Pfam. We carried out a significant comparison to the structural classification database, namely the Evolutionary Classification of Protein Domains (ECOD) that led to the creation of 825 new families based on their set of uncharacterized families (EUFs). Furthermore, we also connected Pfam entries to the Sequence Ontology (SO) through mapping of the Pfam type definitions to SO terms. Since Pfam has many community contributors, we recently enabled the linking between authorship of all Pfam entries with the corresponding authors' ORCID identifiers. This effectively permits authors to claim credit for their Pfam curation and link them to their ORCID record."}68{"work_id": 4384652177, "title": "MitoHiFi: a python pipeline for mitochondrial genome assembly from PacBio high fidelity reads", "abstract": "BACKGROUND: PacBio high fidelity (HiFi) sequencing reads are both long (15-20 kb) and highly accurate (> Q20). Because of these properties, they have revolutionised genome assembly leading to more accurate and contiguous genomes. In eukaryotes the mitochondrial genome is sequenced alongside the nuclear genome often at very high coverage. A dedicated tool for mitochondrial genome assembly using HiFi reads is still missing. RESULTS: MitoHiFi was developed within the Darwin Tree of Life Project to assemble mitochondrial genomes from the HiFi reads generated for target species. The input for MitoHiFi is either the raw reads or the assembled contigs, and the tool outputs a mitochondrial genome sequence fasta file along with annotation of protein and RNA genes. Variants arising from heteroplasmy are assembled independently, and nuclear insertions of mitochondrial sequences are identified and not used in organellar genome assembly. MitoHiFi has been used to assemble 374 mitochondrial genomes (368 Metazoa and 6 Fungi species) for the Darwin Tree of Life Project, the Vertebrate Genomes Project and the Aquatic Symbiosis Genome Project. Inspection of 60 mitochondrial genomes assembled with MitoHiFi for species that already have reference sequences in public databases showed the widespread presence of previously unreported repeats. CONCLUSIONS: MitoHiFi is able to assemble mitochondrial genomes from a wide phylogenetic range of taxa from Pacbio HiFi data. MitoHiFi is written in python and is freely available on GitHub ( https://github.com/marcelauliano/MitoHiFi ). MitoHiFi is available with its dependencies as a Docker container on GitHub (ghcr.io/marcelauliano/mitohifi:master)."}69{"work_id": 4386740800, "title": "CHGNet as a pretrained universal neural network potential for charge-informed atomistic modelling", "abstract": "Abstract Large-scale simulations with complex electron interactions remain one of the greatest challenges for atomistic modelling. Although classical force fields often fail to describe the coupling between electronic states and ionic rearrangements, the more accurate ab initio molecular dynamics suffers from computational complexity that prevents long-time and large-scale simulations, which are essential to study technologically relevant phenomena. Here we present the Crystal Hamiltonian Graph Neural Network (CHGNet), a graph neural network-based machine-learning interatomic potential (MLIP) that models the universal potential energy surface. CHGNet is pretrained on the energies, forces, stresses and magnetic moments from the Materials Project Trajectory Dataset, which consists of over 10 years of density functional theory calculations of more than 1.5 million inorganic structures. The explicit inclusion of magnetic moments enables CHGNet to learn and accurately represent the orbital occupancy of electrons, enhancing its capability to describe both atomic and electronic degrees of freedom. We demonstrate several applications of CHGNet in solid-state materials, including charge-informed molecular dynamics in Li x MnO 2 , the finite temperature phase diagram for Li x FePO 4 and Li diffusion in garnet conductors. We highlight the significance of charge information for capturing appropriate chemistry and provide insights into ionic systems with additional electronic degrees of freedom that cannot be observed by previous MLIPs."}70{"work_id": 2900569176, "title": "STRING v11: protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets", "abstract": "Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein-protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein-protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/."}71{"work_id": 3112376646, "title": "UniProt: the universal protein knowledgebase in 2021", "abstract": "The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/."}72{"work_id": 4406405186, "title": "The design space of E(3)-equivariant atom-centred interatomic potentials", "abstract": "Molecular dynamics simulation is an important tool in computational materials science and chemistry, and in the past decade it has been revolutionized by machine learning. This rapid progress in machine learning interatomic potentials has produced a number of new architectures in just the past few years. Particularly notable among these are the atomic cluster expansion, which unified many of the earlier ideas around atom-density-based descriptors, and Neural Equivariant Interatomic Potentials (NequIP), a message-passing neural network with equivariant features that exhibited state-of-the-art accuracy at the time. Here we construct a mathematical framework that unifies these models: atomic cluster expansion is extended and recast as one layer of a multi-layer architecture, while the linearized version of NequIP is understood as a particular sparsification of a much larger polynomial model. Our framework also provides a practical tool for systematically probing different choices in this unified design space. An ablation study of NequIP, via a set of experiments looking at in- and out-of-domain accuracy and smooth extrapolation very far from the training data, sheds some light on which design choices are critical to achieving high accuracy. A much-simplified version of NequIP, which we call BOTnet (for body-ordered tensor network), has an interpretable architecture and maintains its accuracy on benchmark datasets."}73{"work_id": 3159995035, "title": "MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights", "abstract": "Since its first release over a decade ago, the MetaboAnalyst web-based platform has become widely used for comprehensive metabolomics data analysis and interpretation. Here we introduce MetaboAnalyst version 5.0, aiming to narrow the gap from raw data to functional insights for global metabolomics based on high-resolution mass spectrometry (HRMS). Three modules have been developed to help achieve this goal, including: (i) a LC-MS Spectra Processing module which offers an easy-to-use pipeline that can perform automated parameter optimization and resumable analysis to significantly lower the barriers to LC-MS1 spectra processing; (ii) a Functional Analysis module which expands the previous MS Peaks to Pathways module to allow users to intuitively select any peak groups of interest and evaluate their enrichment of potential functions as defined by metabolic pathways and metabolite sets; (iii) a Functional Meta-Analysis module to combine multiple global metabolomics datasets obtained under complementary conditions or from similar studies to arrive at comprehensive functional insights. There are many other new functions including weighted joint-pathway analysis, data-driven network analysis, batch effect correction, merging technical replicates, improved compound name matching, etc. The web interface, graphics and underlying codebase have also been refactored to improve performance and user experience. At the end of an analysis session, users can now easily switch to other compatible modules for a more streamlined data analysis. MetaboAnalyst 5.0 is freely available at https://www.metaboanalyst.ca."}74{"work_id": 4368358469, "title": "antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation", "abstract": "Microorganisms produce small bioactive compounds as part of their secondary or specialised metabolism. Often, such metabolites have antimicrobial, anticancer, antifungal, antiviral or other bio-activities and thus play an important role for applications in medicine and agriculture. In the past decade, genome mining has become a widely-used method to explore, access, and analyse the available biodiversity of these compounds. Since 2011, the 'antibiotics and secondary metabolite analysis shell-antiSMASH' (https://antismash.secondarymetabolites.org/) has supported researchers in their microbial genome mining tasks, both as a free to use web server and as a standalone tool under an OSI-approved open source licence. It is currently the most widely used tool for detecting and characterising biosynthetic gene clusters (BGCs) in archaea, bacteria, and fungi. Here, we present the updated version 7 of antiSMASH. antiSMASH 7 increases the number of supported cluster types from 71 to 81, as well as containing improvements in the areas of chemical structure prediction, enzymatic assembly-line visualisation and gene cluster regulation."}75{"work_id": 3161596995, "title": "antiSMASH 6.0: improving cluster detection and comparison capabilities", "abstract": "Many microorganisms produce natural products that form the basis of antimicrobials, antivirals, and other drugs. Genome mining is routinely used to complement screening-based workflows to discover novel natural products. Since 2011, the \"antibiotics and secondary metabolite analysis shell-antiSMASH\" (https://antismash.secondarymetabolites.org/) has supported researchers in their microbial genome mining tasks, both as a free-to-use web server and as a standalone tool under an OSI-approved open-source license. It is currently the most widely used tool for detecting and characterising biosynthetic gene clusters (BGCs) in bacteria and fungi. Here, we present the updated version 6 of antiSMASH. antiSMASH 6 increases the number of supported cluster types from 58 to 71, displays the modular structure of multi-modular BGCs, adds a new BGC comparison algorithm, allows for the integration of results from other prediction tools, and more effectively detects tailoring enzymes in RiPP clusters."}76{"work_id": 4309506674, "title": "UniProt: the Universal Protein Knowledgebase in 2023", "abstract": "The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this publication we describe enhancements made to our data processing pipeline and to our website to adapt to an ever-increasing information content. The number of sequences in UniProtKB has risen to over 227 million and we are working towards including a reference proteome for each taxonomic group. We continue to extract detailed annotations from the literature to update or create reviewed entries, while unreviewed entries are supplemented with annotations provided by automated systems using a variety of machine-learning techniques. In addition, the scientific community continues their contributions of publications and annotations to UniProt entries of their interest. Finally, we describe our new website (https://www.uniprot.org/), designed to enhance our users' experience and make our data easily accessible to the research community. This interface includes access to AlphaFold structures for more than 85% of all entries as well as improved visualisations for subcellular localisation of proteins."}77{"work_id": 4406406714, "title": "Battery lifetime prediction across diverse ageing conditions with inter-cell deep learning", "abstract": "Abstract Accurately predicting battery lifetime in early cycles holds tremendous value in real-world applications. However, this task poses significant challenges due to diverse factors influencing complex battery capacity degradation, such as cycling protocols, ambient temperatures and electrode materials. Moreover, cycling under specific conditions is both resource-intensive and time-consuming. Existing predictive models, primarily developed and validated within a restricted set of ageing conditions, thus raise doubts regarding their extensive applicability. Here we introduce BatLiNet, a deep learning framework tailored to predict battery lifetime reliably across a variety of ageing conditions. The distinctive design is integrating an inter-cell learning mechanism to predict the lifetime differences between two battery cells. This mechanism, when combined with conventional single-cell learning, enhances the stability of lifetime predictions for a target cell under varied ageing conditions. Our experimental results, derived from a broad spectrum of ageing conditions, demonstrate BatLiNet\u2019s superior accuracy and robustness compared to existing models. BatLiNet also exhibits transferring capabilities across different battery chemistries, benefitting scenarios with limited resources. We expect this study could promote exploration of cross-cell insights and facilitate battery research across comprehensive ageing factors."}78{"work_id": 2938574745, "title": "The EMBL-EBI search and sequence analysis tools APIs in 2019", "abstract": "The EMBL-EBI provides free access to popular bioinformatics sequence analysis applications as well as to a full-featured text search engine with powerful cross-referencing and data retrieval capabilities. Access to these services is provided via user-friendly web interfaces and via established RESTful and SOAP Web Services APIs (https://www.ebi.ac.uk/seqdb/confluence/display/JDSAT/EMBL-EBI+Web+Services+APIs+-+Data+Retrieval). Both systems have been developed with the same core principles that allow them to integrate an ever-increasing volume of biological data, making them an integral part of many popular data resources provided at the EMBL-EBI. Here, we describe the latest improvements made to the frameworks which enhance the interconnectivity between public EMBL-EBI resources and ultimately enhance biological data discoverability, accessibility, interoperability and reusability."}79{"work_id": 3211795435, "title": "AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models", "abstract": "The AlphaFold Protein Structure Database (AlphaFold DB, https://alphafold.ebi.ac.uk) is an openly accessible, extensive database of high-accuracy protein-structure predictions. Powered by AlphaFold v2.0 of DeepMind, it has enabled an unprecedented expansion of the structural coverage of the known protein-sequence space. AlphaFold DB provides programmatic access to and interactive visualization of predicted atomic coordinates, per-residue and pairwise model-confidence estimates and predicted aligned errors. The initial release of AlphaFold DB contains over 360,000 predicted structures across 21 model-organism proteomes, which will soon be expanded to cover most of the (over 100 million) representative sequences from the UniRef90 data set."}80{"work_id": 2942829220, "title": "antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline", "abstract": "Secondary metabolites produced by bacteria and fungi are an important source of antimicrobials and other bioactive compounds. In recent years, genome mining has seen broad applications in identifying and characterizing new compounds as well as in metabolic engineering. Since 2011, the 'antibiotics and secondary metabolite analysis shell-antiSMASH' (https://antismash.secondarymetabolites.org) has assisted researchers in this, both as a web server and a standalone tool. It has established itself as the most widely used tool for identifying and analysing biosynthetic gene clusters (BGCs) in bacterial and fungal genome sequences. Here, we present an entirely redesigned and extended version 5 of antiSMASH. antiSMASH 5 adds detection rules for clusters encoding the biosynthesis of acyl-amino acids, \u03b2-lactones, fungal RiPPs, RaS-RiPPs, polybrominated diphenyl ethers, C-nucleosides, PPY-like ketones and lipolanthines. For type II polyketide synthase-encoding gene clusters, antiSMASH 5 now offers more detailed predictions. The HTML output visualization has been redesigned to improve the navigation and visual representation of annotations. We have again improved the runtime of analysis steps, making it possible to deliver comprehensive annotations for bacterial genomes within a few minutes. A new output file in the standard JavaScript object notation (JSON) format is aimed at downstream tools that process antiSMASH results programmatically."}81{"work_id": 4220831425, "title": "DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update)", "abstract": "DAVID is a popular bioinformatics resource system including a web server and web service for functional annotation and enrichment analyses of gene lists. It consists of a comprehensive knowledgebase and a set of functional analysis tools. Here, we report all updates made in 2021. The DAVID Gene system was rebuilt to gain coverage of more organisms, which increased the taxonomy coverage from 17 399 to 55 464. All existing annotation types have been updated, if available, based on the new DAVID Gene system. Compared with the last version, the number of gene-term records for most annotation types within the updated Knowledgebase have significantly increased. Moreover, we have incorporated new annotations in the Knowledgebase including small molecule-gene interactions from PubChem, drug-gene interactions from DrugBank, tissue expression information from the Human Protein Atlas, disease information from DisGeNET, and pathways from WikiPathways and PathBank. Eight of ten subgroups split from Uniprot Keyword annotation were assigned to specific types. Finally, we added a species parameter for uploading a list of gene symbols to minimize the ambiguity between species, which increases the efficiency of the list upload and eliminates confusion for users. These current updates have significantly expanded the Knowledgebase and enhanced the discovery power of DAVID."}82{"work_id": 2803664483, "title": "MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis", "abstract": "We present a new update to MetaboAnalyst (version 4.0) for comprehensive metabolomic data analysis, interpretation, and integration with other omics data. Since the last major update in 2015, MetaboAnalyst has continued to evolve based on user feedback and technological advancements in the field. For this year's update, four new key features have been added to MetaboAnalyst 4.0, including: (1) real-time R command tracking and display coupled with the release of a companion MetaboAnalystR package; (2) a MS Peaks to Pathways module for prediction of pathway activity from untargeted mass spectral data using the mummichog algorithm; (3) a Biomarker Meta-analysis module for robust biomarker identification through the combination of multiple metabolomic datasets and (4) a Network Explorer module for integrative analysis of metabolomics, metagenomics, and/or transcriptomics data. The user interface of MetaboAnalyst 4.0 has been reengineered to provide a more modern look and feel, as well as to give more space and flexibility to introduce new functions. The underlying knowledgebases (compound libraries, metabolite sets, and metabolic pathways) have also been updated based on the latest data from the Human Metabolome Database (HMDB). A Docker image of MetaboAnalyst is also available to facilitate download and local installation of MetaboAnalyst. MetaboAnalyst 4.0 is freely available at http://metaboanalyst.ca."}83{"work_id": 7154488692, "title": "Lightweight Kolmogorov-Arnold Network with dual-objective optimization for axial capacity prediction of square coal gangue concrete-filled steel tube stub columns based on finite element simulation", "abstract": null}84{"work_id": 3038025793, "title": "VASPKIT: A user-friendly interface facilitating high-throughput computing and analysis using VASP code", "abstract": null}85{"work_id": 3007309629, "title": "A Deep Learning Approach to Antibiotic Discovery", "abstract": null}86{"work_id": 4389991855, "title": "Discovery of a structural class of antibiotics with explainable deep learning", "abstract": null}87{"work_id": 4399728220, "title": "Kolmogorov\u2013Arnold-Informed Neural Network: A Physics-Informed Deep Learning Framework for Solving Pdes Based on Kolmogorov\u2013Arnold Networks", "abstract": null}88{"work_id": 4408339746, "title": "From PINNs to PIKANs: recent advances in physics-informed machine learning", "abstract": null}89{"work_id": 4385490607, "title": "Scientific discovery in the age of artificial intelligence", "abstract": null}90{"work_id": 4393097303, "title": "Generative AI for designing and validating easily synthesizable and structurally novel antibiotics", "abstract": null}91{"work_id": 4407922392, "title": "Large language models for scientific discovery in molecular property prediction", "abstract": null}92{"work_id": 4407925765, "title": "A practical guide to machine learning interatomic potentials \u2013 Status and future", "abstract": null}93{"work_id": 4409069046, "title": "A predictive machine learning force-field framework for liquid electrolyte development", "abstract": null}94{"work_id": 4417522354, "title": "NEP89: universal neuroevolution potential for inorganic and organic materials across 89 elements", "abstract": null}95{"work_id": 2944434778, "title": "The REDCap consortium: Building an international community of software platform partners", "abstract": null}96{"work_id": 2999044305, "title": "Improved protein structure prediction using potentials from deep learning", "abstract": null}97{"work_id": 2962853966, "title": "Global Convergence of ADMM in Nonconvex Nonsmooth Optimization", "abstract": null}98