A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years.

Structure-based virtual screening (SBVS), also known as molecular docking, has been increasingly applied to discover small-molecule ligands based on the protein structures in the early stage of drug discovery. In this review, we comprehensively surveyed the prospective applications of molecular docking judged by solid experimental validations in the literature over the past fifteen years. Herein, we systematically analyzed the novelty of the targets and the docking hits, practical protocols of docking screening, and the following experimental validations. Among the 419 case studies we reviewed, most virtual screenings were carried out on widely studied targets, and only 22% were on less-explored new targets. Regarding docking software, GLIDE is the most popular one used in molecular docking, while the DOCK 3 series showed a strong capacity for large-scale virtual screening. Besides, the majority of identified hits are promising in structural novelty and one-quarter of the hits showed better potency than 1 µM, indicating that the primary advantage of SBVS is to discover new chemotypes rather than highly potent compounds. Furthermore, in most studies, only in vitro bioassays were carried out to validate the docking hits, which might limit the further characterization and development of the identified active compounds. Finally, several successful stories of SBVS with extensive experimental validations have been highlighted, which provide unique insights into future SBVS drug discovery campaigns.

PeakDetective: A Semisupervised Deep Learning-Based Approach for Peak Curation in Untargeted Metabolomics.

Peak-detection algorithms currently used to process untargeted metabolomics data were designed to maximize sensitivity at the sacrifice of selectively. Peak lists returned by conventional software tools therefore contain a high density of artifacts that do not represent real chemical analytes, which, in turn, hinder downstream analyses. Although some innovative approaches to remove artifacts have recently been introduced, they involve extensive user intervention due to the diversity of peak shapes present within and across metabolomics data sets. To address this bottleneck in metabolomics data processing, we developed a semisupervised deep learning-based approach, PeakDetective, for classification of detected peaks as artifacts or true peaks. Our approach utilizes two techniques for artifact removal. First, an unsupervised autoencoder is used to extract a low-dimensional, latent representation of each peak. Second, a classifier is trained with active learning to discriminate between artifacts and true peaks. Through active learning, the classifier is trained with less than 100 user-labeled peaks in a matter of minutes. Given the speed of its training, PeakDetective can be rapidly tailored to specific LC/MS methods and sample types to maximize performance on each type of data set. In addition to curation, the trained models can also be utilized for peak detection to immediately detect peaks with both high sensitivity and selectivity. We validated PeakDetective on five diverse LC/MS data sets, where PeakDetective showed greater accuracy compared to current approaches. When applied to a SARS-CoV-2 data set, PeakDetective enabled more statistically significant metabolites to be detected. PeakDetective is open source and available as a Python package at https://github.com/pattilab/PeakDetective.

Visual analysis of the prevention and control measures of COVID-19 in Chinese ports.

In 2022, COVID-19 solutions in China have entered a normal stage, and the solutions imported from ports have been transformed from emergency prevention and control measures to investigative long-term prevention and control measures. Therefore, it is necessary to study solutions for COVID-19 at border ports. In this study, 170 research papers related to the prevention and control measures of COVID-19 at ports from 2020 to September 2022 were retrieved from Wanfang database, HowNet database, Wip database, and WoS core collection. Citespace 6.1.R2 software was used to research institutions visualize and analyze researchers and keywords to explore their research hotspots and trends. After analysis, the overall volume of documents issued in the past 3 years was stable. The major contributors are scientific research teams such as the Chinese Academy of Inspection and Quarantine Sciences (Han Hui et al.) and Beijing Customs (Sun Xiaodong et al.), with less cross-agency cooperation. The top five high-frequency keywords with cumulative frequency are as follows: COVID-19 (29 times), epidemic prevention and control (29 times), ports (28 times), health quarantine (16 times), and risk assessment (16 times). The research hotspots in the field of prevention and control measures for COVID-19 at ports are constantly changing with the progress of epidemic prevention and control. Cooperation between research institutions needs to be strengthened urgently. The research hotspots are the imported epidemic prevention and control, risk assessment, port health quarantine, and the normalized epidemic prevention and control mechanism, which is the trend of research and needs further exploration in the future.

Medicine in the Era of Artificial Intelligence: Hey Chatbot, Write Me an H&P.

This Perspective envisions a world where artificial intelligence is integrated into health care.

Bibliometric analysis of the classic cited papers in the American Journal of Surgery: Citation recapitulates surgical history.

BACKGROUND: We performed a bibliometric analysis of the American Journal of Surgery (AJS) to identify, characterize and place within a historical context, its published classic cited papers (CCPs). METHODS: Bibliometric data from papers published in the AJS between January 1, 1945, and December 31, 2021 was extracted from the Web of Science database. Analysis was performed utilizing Bibliometrix and VOSViewer software. RESULTS: 27,070 papers were published in the AJS over the study period. There were 16 CCPs, including 5 Top CCPs, identified. Review of the Top CCPs reveals that they are based on careful clinical observations, innovation and generally build on prior published work. Top CCPs usually are specific to a particular diagnosis or a commonly performed procedure, as such papers frequently present a scoring or classification system, or important details related to new operative approaches or techniques. CONCLUSIONS: Bibliometric study of the AJS has allowed for identification, characterization and appreciation of many of the key changes that have occurred in the discipline throughout the history of modern surgery.

Insights into the FAIRness of the German Network University Medicine: A Survey.

The need to harness large amounts of data, possibly within a short period of time, became apparent during the Covid-19 pandemic outbreak. In 2022, the Corona Data Exchange Platform (CODEX), which had been developed within the German Network University Medicine (NUM), was extended by a number of common components, including a section on FAIR science. The FAIR principles enable research networks to evaluate how well they comply with current standards in open and reproducible science. To be more transparent, but also to guide scientists on how to improve data and software reusability, we disseminated an online survey within the NUM. Here we present the outcomes and lessons learnt.

nCoVDock2: a docking server to predict the binding modes between COVID-19 targets and its potential ligands.

The rapid emergence of SARS-CoV-2 variants with multi-sites mutations is considered as a major obstacle for the development of drugs and vaccines. Although most of the functional proteins essential for SARS-CoV-2 have been determined, the understanding of the COVID-19 target-ligand interactions remains a key challenge. The old version of this COVID-19 docking server was built in 2020, and free and open to all users. Here, we present nCoVDock2, a new docking server to predict the binding modes for targets from SARS-CoV-2. First, the new server supports more targets. We replaced the modeled structures with newly resolved structures and added more potential targets of COVID-19, especially for the variants. Second, for small molecule docking, Autodock Vina was upgraded to the latest version 1.2.0, and a new scoring function was added for peptide or antibody docking. Third, the input interface and molecular visualization were updated for a better user experience. The web server, together with an extensive help and tutorial, are freely available at: https://ncovdock2.schanglab.org.cn.

Exploring Use Cases for CovidGraph.

HealthECCO is the driving force behind the COVID-19 knowledge graph spanning multiple biomedical data domains. One way to access CovidGraph is SemSpect, an interface designed for data exploration in graphs. To showcase the possibilities that arise from integrating a variety of COVID-19 related data sources over the last three years, we present three use cases from the (bio-)medical domain. Availability: The project is open source and freely available from: https://healthecco.org/covidgraph/. The source code and documentation are available on GitHub: https://github.com/covidgraph.

Building a collaborative cloud platform to accelerate heart, lung, blood, and sleep research.

Research increasingly relies on interrogating large-scale data resources. The NIH National Heart, Lung, and Blood Institute developed the NHLBI BioData CatalystⓇ (BDC), a community-driven ecosystem where researchers, including bench and clinical scientists, statisticians, and algorithm developers, find, access, share, store, and compute on large-scale datasets. This ecosystem provides secure, cloud-based workspaces, user authentication and authorization, search, tools and workflows, applications, and new innovative features to address community needs, including exploratory data analysis, genomic and imaging tools, tools for reproducibility, and improved interoperability with other NIH data science platforms. BDC offers straightforward access to large-scale datasets and computational resources that support precision medicine for heart, lung, blood, and sleep conditions, leveraging separately developed and managed platforms to maximize flexibility based on researcher needs, expertise, and backgrounds. Through the NHLBI BioData Catalyst Fellows Program, BDC facilitates scientific discoveries and technological advances. BDC also facilitated accelerated research on the coronavirus disease-2019 (COVID-19) pandemic.

An improved golden jackal optimization for multilevel thresholding image segmentation.

Aerial photography is a long-range, non-contact method of target detection technology that enables qualitative or quantitative analysis of the target. However, aerial photography images generally have certain chromatic aberration and color distortion. Therefore, effective segmentation of aerial images can further enhance the feature information and reduce the computational difficulty for subsequent image processing. In this paper, we propose an improved version of Golden Jackal Optimization, which is dubbed Helper Mechanism Based Golden Jackal Optimization (HGJO), to apply multilevel threshold segmentation to aerial images. The proposed method uses opposition-based learning to boost population diversity. And a new approach to calculate the prey escape energy is proposed to improve the convergence speed of the algorithm. In addition, the Cauchy distribution is introduced to adjust the original update scheme to enhance the exploration capability of the algorithm. Finally, a novel "helper mechanism" is designed to improve the performance for escape the local optima. To demonstrate the effectiveness of the proposed algorithm, we use the CEC2022 benchmark function test suite to perform comparison experiments. the HGJO is compared with the original GJO and five classical meta-heuristics. The experimental results show that HGJO is able to achieve competitive results in the benchmark test set. Finally, all of the algorithms are applied to the experiments of variable threshold segmentation of aerial images, and the results show that the aerial photography images segmented by HGJO beat the others. Noteworthy, the source code of HGJO is publicly available at https://github.com/Vang-z/HGJO.

Database Resources of the National Genomics Data Center, China National Center for Bioinformation in 2022.

The National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB), provides a family of database resources to support global research in both academia and industry. With the explosively accumulated multi-omics data at ever-faster rates, CNCB-NGDC is constantly scaling up and updating its core database resources through big data archive, curation, integration and analysis. In the past year, efforts have been made to synthesize the growing data and knowledge, particularly in single-cell omics and precision medicine research, and a series of resources have been newly developed, updated and enhanced. Moreover, CNCB-NGDC has continued to daily update SARS-CoV-2 genome sequences, variants, haplotypes and literature. Particularly, OpenLB, an open library of bioscience, has been established by providing easy and open access to a substantial number of abstract texts from PubMed, bioRxiv and medRxiv. In addition, Database Commons is significantly updated by cataloguing a full list of global databases, and BLAST tools are newly deployed to provide online sequence search services. All these resources along with their services are publicly accessible at https://ngdc.cncb.ac.cn.

An accessible infrastructure for artificial intelligence using a Docker-based JupyterLab in Galaxy.

BACKGROUND: Artificial intelligence (AI) programs that train on large datasets require powerful compute infrastructure consisting of several CPU cores and GPUs. JupyterLab provides an excellent framework for developing AI programs, but it needs to be hosted on such an infrastructure to enable faster training of AI programs using parallel computing. FINDINGS: An open-source, docker-based, and GPU-enabled JupyterLab infrastructure is developed that runs on the public compute infrastructure of Galaxy Europe consisting of thousands of CPU cores, many GPUs, and several petabytes of storage to rapidly prototype and develop end-to-end AI projects. Using a JupyterLab notebook, long-running AI model training programs can also be executed remotely to create trained models, represented in open neural network exchange (ONNX) format, and other output datasets in Galaxy. Other features include Git integration for version control, the option of creating and executing pipelines of notebooks, and multiple dashboards and packages for monitoring compute resources and visualization, respectively. CONCLUSIONS: These features make JupyterLab in Galaxy Europe highly suitable for creating and managing AI projects. A recent scientific publication that predicts infected regions in COVID-19 computed tomography scan images is reproduced using various features of JupyterLab on Galaxy Europe. In addition, ColabFold, a faster implementation of AlphaFold2, is accessed in JupyterLab to predict the 3-dimensional structure of protein sequences. JupyterLab is accessible in 2 ways-one as an interactive Galaxy tool and the other by running the underlying Docker container. In both ways, long-running training can be executed on Galaxy's compute infrastructure. Scripts to create the Docker container are available under MIT license at https://github.com/usegalaxy-eu/gpu-jupyterlab-docker.

Analysis of Publication Activity and Research Trends in the Field of AI Medical Applications: Network Approach.

Artificial intelligence (AI) has revolutionized numerous industries, including medicine. In recent years, the integration of AI into medical practices has shown great promise in enhancing the accuracy and efficiency of diagnosing diseases, predicting patient outcomes, and personalizing treatment plans. This paper aims at the exploration of the AI-based medicine research using network approach and analysis of existing trends based on PubMed. Our findings are based on the results of PubMed search queries and analysis of the number of papers obtained by the different search queries. Our goal is to explore how are the AI-based methods used in healthcare research, which approaches and techniques are the most popular, and to discuss the potential reasoning behind the obtained results. Using analysis of the co-occurrence network constructed using VOSviewer software, we detected the main clusters of interest in AI-based healthcare research. Then, we proceeded with the thorough analysis of publication activity in various categories of medical AI research, including research on different AI-based methods applied to different types of medical data. We analyzed the results of query processing in the PubMed database over the past 5 years obtained via a specifically designed strategy for generating search queries based on the thorough selection of keywords from different categories of interest. We provide a comprehensive analysis of existing applications of AI-based methods to medical data of different modalities, including the context of various medical fields and specific diseases that carry the greatest danger to the human population.

A multicenter evaluation of a deep learning software (LungQuant) for lung parenchyma characterization in COVID-19 pneumonia.

BACKGROUND: The role of computed tomography (CT) in the diagnosis and characterization of coronavirus disease 2019 (COVID-19) pneumonia has been widely recognized. We evaluated the performance of a software for quantitative analysis of chest CT, the LungQuant system, by comparing its results with independent visual evaluations by a group of 14 clinical experts. The aim of this work is to evaluate the ability of the automated tool to extract quantitative information from lung CT, relevant for the design of a diagnosis support model. METHODS: LungQuant segments both the lungs and lesions associated with COVID-19 pneumonia (ground-glass opacities and consolidations) and computes derived quantities corresponding to qualitative characteristics used to clinically assess COVID-19 lesions. The comparison was carried out on 120 publicly available CT scans of patients affected by COVID-19 pneumonia. Scans were scored for four qualitative metrics: percentage of lung involvement, type of lesion, and two disease distribution scores. We evaluated the agreement between the LungQuant output and the visual assessments through receiver operating characteristics area under the curve (AUC) analysis and by fitting a nonlinear regression model. RESULTS: Despite the rather large heterogeneity in the qualitative labels assigned by the clinical experts for each metric, we found good agreement on the metrics compared to the LungQuant output. The AUC values obtained for the four qualitative metrics were 0.98, 0.85, 0.90, and 0.81. CONCLUSIONS: Visual clinical evaluation could be complemented and supported by computer-aided quantification, whose values match the average evaluation of several independent clinical experts. KEY POINTS: We conducted a multicenter evaluation of the deep learning-based LungQuant automated software. We translated qualitative assessments into quantifiable metrics to characterize coronavirus disease 2019 (COVID-19) pneumonia lesions. Comparing the software output to the clinical evaluations, results were satisfactory despite heterogeneity of the clinical evaluations. An automatic quantification tool may contribute to improve the clinical workflow of COVID-19 pneumonia.

A distributed computing model for big data anonymization in the networks.

Recently big data and its applications had sharp growth in various fields such as IoT, bioinformatics, eCommerce, and social media. The huge volume of data incurred enormous challenges to the architecture, infrastructure, and computing capacity of IT systems. Therefore, the compelling need of the scientific and industrial community is large-scale and robust computing systems. Since one of the characteristics of big data is value, data should be published for analysts to extract useful patterns from them. However, data publishing may lead to the disclosure of individuals' private information. Among the modern parallel computing platforms, Apache Spark is a fast and in-memory computing framework for large-scale data processing that provides high scalability by introducing the resilient distributed dataset (RDDs). In terms of performance, Due to in-memory computations, it is 100 times faster than Hadoop. Therefore, Apache Spark is one of the essential frameworks to implement distributed methods for privacy-preserving in big data publishing (PPBDP). This paper uses the RDD programming of Apache Spark to propose an efficient parallel implementation of a new computing model for big data anonymization. This computing model has three-phase of in-memory computations to address the runtime, scalability, and performance of large-scale data anonymization. The model supports partition-based data clustering algorithms to preserve the λ-diversity privacy model by using transformation and actions on RDDs. Therefore, the authors have investigated Spark-based implementation for preserving the λ-diversity privacy model by two designed City block and Pearson distance functions. The results of the paper provide a comprehensive guideline allowing the researchers to apply Apache Spark in their own researches.

An implementation framework to improve the transparency and reproducibility of computational models of infectious diseases.

Computational models of infectious diseases have become valuable tools for research and the public health response against epidemic threats. The reproducibility of computational models has been limited, undermining the scientific process and possibly trust in modeling results and related response strategies, such as vaccination. We translated published reproducibility guidelines from a wide range of scientific disciplines into an implementation framework for improving reproducibility of infectious disease computational models. The framework comprises 22 elements that should be described, grouped into 6 categories: computational environment, analytical software, model description, model implementation, data, and experimental protocol. The framework can be used by scientific communities to develop actionable tools for sharing computational models in a reproducible way.

Scoliosis Management through Apps and Software Tools.

Background: Scoliosis is curvature of the spine, often found in adolescents, which can impact on quality of life. Generally, scoliosis is diagnosed by measuring the Cobb angle, which represents the gold standard for scoliosis grade quantification. Commonly, scoliosis evaluation is conducted in person by medical professionals using traditional methods (i.e., involving a scoliometer and/or X-ray radiographs). In recent years, as has happened in various medicine disciplines, it is possible also in orthopedics to observe the spread of Information and Communications Technology (ICT) solutions (i.e., software-based approaches). As an example, smartphone applications (apps) and web-based applications may help the doctors in screening and monitoring scoliosis, thereby reducing the number of in-person visits. Objectives: This paper aims to provide an overview of the main features of the most popular scoliosis ICT tools, i.e., apps and web-based applications for scoliosis diagnosis, screening, and monitoring. Several apps are assessed and compared with the aim of providing a valid starting point for doctors and patients in their choice of software-based tools. Benefits for the patients may be: reducing the number of visits to the doctor, self-monitoring of scoliosis. Benefits for the doctors may be: monitoring the scoliosis progression over time, managing several patients in a remote way, mining the data of several patients for evaluating different therapeutic or exercise prescriptions. Materials and Methods: We first propose a methodology for the evaluation of scoliosis apps in which five macro-categories are considered: (i) technological aspects (e.g., available sensors, how angles are measured); (ii) the type of measurements (e.g., Cobb angle, angle of trunk rotation, axial vertebral rotation); (iii) availability (e.g., app store and eventual fee to pay); (iv) the functions offered to the user (e.g., posture monitoring, exercise prescription); (v) overall evaluation (e.g., pros and cons, usability). Then, six apps and one web-based application are described and evaluated using this methodology. Results: The results for assessment of scoliosis apps are shown in a tabular format for ease of understanding and intuitive comparison, which can help the doctors, specialists, and families in their choice of scoliosis apps. Conclusions: The use of ICT solutions for spinal curvature assessment and monitoring brings several advantages to both patients and orthopedics specialists. Six scoliosis apps and one web-based application are evaluated, and a guideline for their selection is provided.

MSClustering: A Cytoscape Tool for Multi-Level Clustering of Biological Networks.

MSClustering is an efficient software package for visualizing and analyzing complex networks in Cytoscape. Based on the distance matrix of a network that it takes as input, MSClustering automatically displays the minimum span clustering (MSC) of the network at various characteristic levels. To produce a view of the overall network structure, the app then organizes the multi-level results into an MSC tree. Here, we demonstrate the package's phylogenetic applications in studying the evolutionary relationships of complex systems, including 63 beta coronaviruses and 197 GPCRs. The validity of MSClustering for large systems has been verified by its clustering of 3481 enzymes. Through an experimental comparison, we show that MSClustering outperforms five different state-of-the-art methods in the efficiency and reliability of their clustering.

ThermalProGAN: A sequence-based thermally stable protein generator trained using unpaired data.

MOTIVATION: The synthesis of proteins with novel desired properties is challenging but sought after by the industry and academia. The dominating approach is based on trial-and-error inducing point mutations, assisted by structural information or predictive models built with paired data that are difficult to collect. This study proposes a sequence-based unpaired-sample of novel protein inventor (SUNI) to build ThermalProGAN for generating thermally stable proteins based on sequence information. RESULTS: The ThermalProGAN can strongly mutate the input sequence with a median number of 32 residues. A known normal protein, 1RG0, was used to generate a thermally stable form by mutating 51 residues. After superimposing the two structures, high similarity is shown, indicating that the basic function would be conserved. Eighty four molecular dynamics simulation results of 1RG0 and the COVID-19 vaccine candidates with a total simulation time of 840[Formula: see text]ns indicate that the thermal stability increased. CONCLUSION: This proof of concept demonstrated that transfer of a desired protein property from one set of proteins is feasible. Availability and implementation: The source code of ThermalProGAN can be freely accessed at https://github.com/markliou/ThermalProGAN/ with an MIT license. The website is https://thermalprogan.markliou.tw:433. Supplementary information: Supplementary data are available on Github.

Galaxy Training: A powerful framework for teaching!

There is an ongoing explosion of scientific datasets being generated, brought on by recent technological advances in many areas of the natural sciences. As a result, the life sciences have become increasingly computational in nature, and bioinformatics has taken on a central role in research studies. However, basic computational skills, data analysis, and stewardship are still rarely taught in life science educational programs, resulting in a skills gap in many of the researchers tasked with analysing these big datasets. In order to address this skills gap and empower researchers to perform their own data analyses, the Galaxy Training Network (GTN) has previously developed the Galaxy Training Platform (https://training.galaxyproject.org), an open access, community-driven framework for the collection of FAIR (Findable, Accessible, Interoperable, Reusable) training materials for data analysis utilizing the user-friendly Galaxy framework as its primary data analysis platform. Since its inception, this training platform has thrived, with the number of tutorials and contributors growing rapidly, and the range of topics extending beyond life sciences to include topics such as climatology, cheminformatics, and machine learning. While initially aimed at supporting researchers directly, the GTN framework has proven to be an invaluable resource for educators as well. We have focused our efforts in recent years on adding increased support for this growing community of instructors. New features have been added to facilitate the use of the materials in a classroom setting, simplifying the contribution flow for new materials, and have added a set of train-the-trainer lessons. Here, we present the latest developments in the GTN project, aimed at facilitating the use of the Galaxy Training materials by educators, and its usage in different learning environments.