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Background: Multiple sequence alignment (MSA) has proven extremely useful in computational biology, especially in inferring evolutionary relationships via phylogenetic analysis and providing insight into protein structure and function. An alternative to the standard MSA model is partial order alignment (POA), in which aligned sequences are represented as paths in a graph rather than rows in a matrix. While the POA model has proven useful in several applications (e.g. sequencing reads assembly and pangenome structure exploration), we lack efficient visualization tools that could highlight its advantages. Results: We propose Sequence Flow – a web application designed to address the above problem. Sequence Flow presents the POA as a Sankey diagram, a kind of graph visualisation typically used for graphs representing flowcharts. Sequence Flow enables interactive alignment exploration, including fragment selection, highlighting a selected group of sequences, modification of the position of graph nodes, structure simplification etc. After adjustment, the visualization can be saved as a high-quality graphic file. Thanks to the use of SanKEY.js – a JavaScript library for creating Sankey diagrams, designed specifically to visualize POAs, Sequence Flow provides satisfactory performance even with large alignments. Conclusions: We provide Sankey diagram-based POA visualization tools for both end users (Sequence Flow) and bioinformatic software developers (SanKEY.js). Sequence Flow webservice is available at https://sequenceflow.mimuw.edu.pl/. The source code for SanKEY.js is available at https://github.com/Krzysiekzd/SanKEY.js and for Sequence Flow at https://github.com/Krzysiekzd/SequenceFlow. [ABSTRACT FROM AUTHOR]

N7-Methylguanosine (m7G) is important RNA modification at internal and the cap structure of five terminal end of message RNA. It is essential for RNA stability of RNA, the efficiency of translation, and various intracellular RNA processing pathways. Given the significance of the m7G modification, numerous studies have been conducted to predict m7G sites. To further elucidate the regulatory mechanisms surrounding m7G, we introduce a novel bioinformatics framework, m7GRegpred, designed to forecast the targets of the m7G methyltransferases METTL1 and WDR4, and m7G readers QKI5, QKI6, and QKI7 for the first time. We integrated different features to build predictors, with AUROC scores of 0.856, 0.857, 0.780, 0.776, 0.818 for METTL1, WDR4, QKI5, QKI6, and QKI7, respectively. In addition, the effect of window lengths and algorism were systemically evaluated in this work. The finial model was summarized in a user-friendly webserver: http://modinfor.com/m7GRegpred/. Our research indicates that the substrates of m7G regulators can be identified and may potentially advance the study of m7G regulators under unique conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple sequence alignment (MSA) has proven extremely useful in computational biology, especially in inferring evolutionary relationships via phylogenetic analysis and providing insight into protein structure and function. An alternative to the standard MSA model is partial order alignment (POA), in which aligned sequences are represented as paths in a graph rather than rows in a matrix. While the POA model has proven useful in several applications (e.g. sequencing reads assembly and pangenome structure exploration), we lack efficient visualization tools that could highlight its advantages. Results We propose Sequence Flow – a web application designed to address the above problem. Sequence Flow presents the POA as a Sankey diagram, a kind of graph visualisation typically used for graphs representing flowcharts. Sequence Flow enables interactive alignment exploration, including fragment selection, highlighting a selected group of sequences, modification of the position of graph nodes, structure simplification etc. After adjustment, the visualization can be saved as a high-quality graphic file. Thanks to the use of SanKEY.js – a JavaScript library for creating Sankey diagrams, designed specifically to visualize POAs, Sequence Flow provides satisfactory performance even with large alignments. Conclusions We provide Sankey diagram-based POA visualization tools for both end users (Sequence Flow) and bioinformatic software developers (SanKEY.js). Sequence Flow webservice is available at https://sequenceflow.mimuw.edu.pl/ . The source code for SanKEY.js is available at https://github.com/Krzysiekzd/SanKEY.js and for Sequence Flow at https://github.com/Krzysiekzd/SequenceFlow .

Neuropeptides play critical roles in many biological processes such as growth, learning, memory, metabolism, and neuronal differentiation. A few approaches have been reported for predicting neuropeptides that are cleaved from precursor protein sequences. However, these models for cleavage site prediction of precursors were developed using a limited number of neuropeptide precursor datasets and simple precursors representation models. In addition, a universal method for predicting neuropeptide cleavage sites that can be applied to all species is still lacking. In this paper, we proposed a novel deep learning method called DeepNeuropePred, using a combination of pre-trained language model and Convolutional Neural Networks for feature extraction and predicting the neuropeptide cleavage sites from precursors. To demonstrate the model’s effectiveness and robustness, we evaluated the performance of DeepNeuropePred and four models from the NeuroPred server in the independent dataset and our model achieved the highest AUC score (0.916), which are 6.9%, 7.8%, 8.8%, and 10.9% higher than Mammalian (0.857), insects (0.850), Mollusc (0.842) and Motif (0.826), respectively. For the convenience of researchers, we provide a web server (http://isyslab.info/NeuroPepV2/deepNeuropePred.jsp).

Determining the physicochemical properties of a protein can reveal important insights in their structure, biological functions, stability, and interactions with other molecules. Although tools for computing properties of proteins already existed, we could not find a comprehensive tool that enables the calculations of multiple properties for multiple input proteins on the proteome level at once. Facing this limitation, we developed Multiple Protein Profiler (MPP) 1.0 as an integrated tool that allows the profiling of 12 individual properties of multiple proteins in a significant manner. MPP provides a tabular and graphic visualization of properties of multiple proteins. The tool is freely accessible at https://mproteinprofiler.microbiologyandimmunology.dal.ca/. [ABSTRACT FROM AUTHOR]

This research contains the design of an Industrial Network using the Industrial Ethernet-based communication protocol (Profinet) applied to the electro-pneumatic control of a distributed system of discrete processes, with the purpose of establishing a send/receive of data between an S7-1200 controller that acts as a server and two LOGO controllers that act as clients. For this network, local monitoring was established through a TP-700 screen, which is linked to the Siemens Sm@rt Client application, which allows monitoring processes from a Pc System and a smartphone mobile device, while activating the WebServer in the controller, which is a server to control and monitor processes on the web. From the study carried out, it is concluded that Profinet is an Ethernet protocol that allows the transfer of data in real time, which is suitable for applications that require a fast response. This protocol uses an industrial Ethernet network that supports high speeds, recommended for applications of high complexity. An important aspect to consider when deploying both the Sm@rt Client application and the WebServer is that they must be connected either wirelessly or by Ethernet cable to the intranet where the processes are implemented in order to ensure that the two applications work correctly. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex Class II (MHCII) proteins initiate and regulate immune responses by presentation of antigenic peptides to CD4+ T-cells and self-restriction. The interactions between MHCII and peptides determine the specificity of the immune response and are crucial in immunotherapy and cancer vaccine design. With the ever-increasing amount of MHCII-peptide binding data available, many computational approaches have been developed for MHCIIpeptide interaction prediction over the last decade. There is thus an urgent need to provide an up-to-date overview and assessment of these newly developed computational methods. To benchmark the prediction performance of these methods, we constructed an independent dataset containing binding and nonbinding peptides to 20 human MHCII protein allotypes from the Immune Epitope Database, covering DP, DR and DQ alleles. After collecting 11 known predictors up to January 2022, we evaluated those available through a webserver or standalone packages on this independent dataset. The benchmarking results show that MixMHC2pred and NetMHCIIpan-4.1 achieve the best performance among all predictors. In general, newly developed methods perform better than older ones due to the rapid expansion of data on which they are trained and the development of deep learning algorithms. Our manuscript not only draws a full picture of the state-of-art of MHCII-peptide binding prediction, but also guides researchers in the choice among the different predictors. More importantly, it will inspire biomedical researchers in both academia and industry for the future developments in this field. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex Class II (MHCII) proteins initiate and regulate immune responses by presentation of antigenic peptides to CD4+ T-cells and self-restriction. The interactions between MHCII and peptides determine the specificity of the immune response and are crucial in immunotherapy and cancer vaccine design. With the ever-increasing amount of MHCII-peptide binding data available, many computational approaches have been developed for MHCII-peptide interaction prediction over the last decade. There is thus an urgent need to provide an up-to-date overview and assessment of these newly developed computational methods. To benchmark the prediction performance of these methods, we constructed an independent dataset containing binding and non-binding peptides to 20 human MHCII protein allotypes from the Immune Epitope Database, covering DP, DR and DQ alleles. After collecting 11 known predictors up to January 2022, we evaluated those available through a webserver or standalone packages on this independent dataset. The benchmarking results show that MixMHC2pred and NetMHCIIpan-4.1 achieve the best performance among all predictors. In general, newly developed methods perform better than older ones due to the rapid expansion of data on which they are trained and the development of deep learning algorithms. Our manuscript not only draws a full picture of the state-of-art of MHCII-peptide binding prediction, but also guides researchers in the choice among the different predictors. More importantly, it will inspire biomedical researchers in both academia and industry for the future developments in this field. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) analysis is crucial for the diagnosis of mitochondrial disorders, forensic investigations, and basic research. Existing pipelines are complex, expensive, and require specialized personnel. In many cases, including the diagnosis of detrimental single nucleotide variants (SNVs), mtDNA analysis is still carried out using Sanger sequencing. Here, we developed a simple workflow and a publicly available webserver named Mitopore that allows the detection of mtDNA SNVs, indels, and haplogroups. To simplify mtDNA analysis, we tailored our workflow to process noisy long-read sequencing data for mtDNA analysis, focusing on sequence alignment and parameter optimization. We implemented Mitopore with eliBQ (eliminate bad quality reads), an innovative quality enhancement that permits the increase of per-base quality of over 20% for low-quality data. The whole Mitopore workflow and webserver were validated using patient-derived and induced pluripotent stem cells harboring mtDNA mutations. Mitopore streamlines mtDNA analysis as an easy-to-use fast, reliable, and cost-effective analysis method for both long- and short-read sequencing data. This significantly enhances the accessibility of mtDNA analysis and reduces the cost per sample, contributing to the progress of mtDNA-related research and diagnosis.

The DNA N6-methyladenine (6mA) is an epigenetic modification, which plays a pivotal role in biological processes encompassing gene expression, DNA replication, repair, and recombination. Therefore, the precise identification of 6mA sites is fundamental for better understanding its function, but challenging. We proposed an improved ensemble-based method for predicting DNA N6-methyladenine sites in cross-species genomes called SoftVoting6mA. The SoftVoting6mA selected four (electron–ion-interaction pseudo potential, One-hot encoding, Kmer, and pseudo dinucleotide composition) codes from 15 types of encoding to represent DNA sequences by comparing their performances. Similarly, the SoftVoting6mA combined four learning algorithms using the soft voting strategy. The 5-fold cross-validation and the independent tests showed that SoftVoting6mA reached the state-of-the-art performance. To enhance accessibility, a user-friendly web server is provided at http://www.biolscience.cn/SoftVoting6mA/.

TELER is a real-time intrusion detection and weblog-based alerting tool that runs on the terminal. TELER is designed to be a fast terminal-based threat analyzer. The IDS (intrusion detection system) is needed to help web administrators secure their servers. This study aims to test the TELER performance as real-time intrusion detection and threat alert. This study tries to implement an open-source application called TELER based on Golang. The IDS testing method on the web server this time uses directory brute force with the result that TELER can detect an attack and provide prompt notification to the web administrator when an attack occurs on the web server. The result of this study shows that the TELER successfully sent notifications to the Telegram, Discord, and Slack applications when an attack or intrusion occurs. Based on the experiments conducted in this study, Slack is the most effective application for receiving directory brute-force attack notifications. The average time for Slack to receive attack information is 0.03 seconds. TELER was successfully proven to detect cyberattacks.

Today, pharmaceutical industry faces great pressure to employ more efficient and systematic ways in drug discovery and development process. However, conventional formulation studies still strongly rely on personal experiences by trial-and-error experiments, resulting in a labor-consuming, tedious and costly pipeline. Thus, it is highly required to develop intelligent and efficient methods for formulation development to keep pace with the progress of the pharmaceutical industry. Here, we developed a comprehensive web-based platform (FormulationAI) for in silico formulation design. First, the most comprehensive datasets of six widely used drug formulation systems in the pharmaceutical industry were collected over 10 years, including cyclodextrin formulation, solid dispersion, phospholipid complex, nanocrystals, self-emulsifying and liposome systems. Then, intelligent prediction and evaluation of 16 important properties from the six systems were investigated and implemented by systematic study and comparison of different AI algorithms and molecular representations. Finally, an efficient prediction platform was established and validated, which enables the formulation design just by inputting basic information of drugs and excipients. FormulationAI is the first freely available comprehensive web-based platform, which provides a powerful solution to assist the formulation design in pharmaceutical industry. It is available at https://formulationai.computpharm.org/. [ABSTRACT FROM AUTHOR]

In Indonesia, the agriculture industry has been more reluctant than other sectors to adopt IoT, IT, and AI technology. Utilizing this technology will enable precision agriculture. This research aims to make and implement an IoT-Webserver-Android and Machine Learning-based soil PH factor monitoring tool system. The steps for making the tool system are divided into three subsystems. The first is a multiple sensors data acquisition subsystem, consisting of sensors for soil PH-Moisture, Temperature-Humidity, and Sunlight. The sensors are connected to the Arduino Uno microcontroller for serial communication with the ESP 8266 microcontroller for the Wi-Fi module. The second part is the monitoring subsystem with the local web application, which contains a MySQL database and a local web page. The third part is the monitoring subsystem with the Android application, which includes a real-time Firebase database and the application for real-time and mobile data display. The results have been implemented and display the expected outcomes. It is clear from the performance of the three subsystems. The outcomes of the tool system's data evaluation provide precise statistical values. Then, Machine Learning analysis generates accurate soil PH prediction models. It has been demonstrated that the monitoring system is applicable and has a favorable impact on data soil PH factor. The implication for the future is that this monitoring system should be added with Nitrogen-Phosphorus-Potassium sensors to measure soil nutrients. Also, the system added edge-analysis to be integrated in monitoring and analyzing soil nutrients. [ABSTRACT FROM AUTHOR]

DNA 5-methylcytosine (5mC) is widely present in multicellular eukaryotes, which plays important roles in various developmental and physiological processes and a wide range of human diseases. Thus, it is essential to accurately detect the 5mC sites. Although current sequencing technologies can map genome-wide 5mC sites, these experimental methods are both costly and time-consuming. To achieve a fast and accurate prediction of 5mC sites, we propose a new computational approach, BERT-5mC. First, we pre-trained a domain-specific BERT (bidirectional encoder representations from transformers) model by using human promoter sequences as language corpus. BERT is a deep two-way language representation model based on Transformer. Second, we fine-tuned the domain-specific BERT model based on the 5mC training dataset to build the model. The cross-validation results show that our model achieves an AUROC of 0.966 which is higher than other state-of-the-art methods such as iPromoter-5mC, 5mC_Pred, and BiLSTM-5mC. Furthermore, our model was evaluated on the independent test set, which shows that our model achieves an AUROC of 0.966 that is also higher than other state-of-the-art methods. Moreover, we analyzed the attention weights generated by BERT to identify a number of nucleotide distributions that are closely associated with 5mC modifications. To facilitate the use of our model, we built a webserver which can be freely accessed at: http://5mc-pred.zhulab.org.cn.

The lymphocyte-specific protein tyrosine kinase (LCK) is a critical target in leukemia treatment. However, potential off-target interactions involving LCK can lead to unintended consequences. This underscores the importance of accurately predicting the inhibitory reactions of drug molecules with LCK during the research and development stage. To address this, we introduce an advanced ensemble machine learning technique designed to estimate the binding affinity between molecules and LCK. This comprehensive method includes the generation and selection of molecular fingerprints, the design of the machine learning model, hyperparameter tuning, and a model ensemble. Through rigorous optimization, the predictive capabilities of our model have been significantly enhanced, raising test R2 values from 0.644 to 0.730 and reducing test RMSE values from 0.841 to 0.732. Utilizing these advancements, our refined ensemble model was employed to screen an MCE -like drug library. Through screening, we selected the top ten scoring compounds, and tested them using the ADP-Glo bioactivity assay. Subsequently, we employed molecular docking techniques to further validate the binding mode analysis of these compounds with LCK. The exceptional predictive accuracy of our model in identifying LCK inhibitors not only emphasizes its effectiveness in projecting LCK-related safety panel predictions but also in discovering new LCK inhibitors. For added user convenience, we have also established a webserver, and a GitHub repository to share the project. [ABSTRACT FROM AUTHOR]

LTR-retrotransposons (LTR-RTs) are a class of RNA-replicating transposon elements (TEs) that can alter genome structure and function by moving positions, repositioning genes, shifting exons, and causing chromosomal rearrangements. LTR-RTs are widespread in many plant genomes and constitute a significant portion of the genome. Their movement and activity in eukaryotic genomes can provide insight into genome evolution and gene function, especially when LTR-RTs are located near or within genes. Building the redundant and non-redundant LTR-RTs libraries and their annotations for species lacking this resource requires extensive bioinformatics pipelines and expensive computing power to analyze large amounts of genomic data. This increases the need for online services that provide computational resources with minimal overhead and maximum efficiency. Here, we present MegaLTR as a web server and standalone pipeline that detects intact LTR-RTs at the whole-genome level and integrates multiple tools for structure-based, homologybased, and de novo identification, classification, annotation, insertion time determination, and LTR-RT gene chimera analysis. MegaLTR also provides statistical analysis and visualization with multiple tools and can be used to accelerate plant species discovery and assist breeding programs in their efforts to improve genomic resources. We hope that the development of online services such as MegaLTR, which can analyze large amounts of genomic data, will become increasingly important for the automated detection and annotation of LTR-RT elements. [ABSTRACT FROM AUTHOR]

The development in the field of cloud webserver management for the execution of the workflow and meeting the quality-of-service (QoS) prerequisites in a distributed cloud environment has been a challenging task. Though, internet of things (IoT) of work presented for the scheduling of the workflow in a heterogeneous cloud environment. Moreover, the rapid development in the field of cloud computing like edge-cloud computing creates new methods to schedule the workflow in a heterogenous cloud environment to process different tasks like IoT, event-driven applications, and different network applications. The current methods used for workflow scheduling have failed to provide better trade-offs to meet reliable performance with minimal delay. In this paper, a novel web server resource management framework is presented namely the reliable and efficient webserver management (REWM) framework for the edge-cloud environment. The experiment is conducted on complex bioinformatic workflows; the result shows the significant reduction of cost and energy by the proposed REWM in comparison with standard webserver management methodology. [ABSTRACT FROM AUTHOR]

Ion mobility coupled to mass spectrometry informs on the shape and size of protein structures in the form of a collision cross section (CCSIM). Although there are several computational methods for predicting CCSIM based on protein structures, including our previously developed projection approximation using rough circular shapes (PARCS), the process usually requires prior experience with the command-line interface. To overcome this challenge, here we present a web application on the Rosetta Online Server that Includes Everyone (ROSIE) webserver to predict CCSIM from protein structure using projection approximation with PARCS. In this web interface, the user is only required to provide one or more PDB files as input. Results from our case studies suggest that CCSIM predictions (with ROSIE-PARCS) are highly accurate with an average error of 6.12%. Furthermore, the absolute difference between CCSIM and CCSPARCS can help in distinguishing accurate from inaccurate AlphaFold2 protein structure predictions. ROSIE-PARCS is designed with a user-friendly interface, is available publicly and is free to use. The ROSIE-PARCS web interface is supported by all major web browsers and can be accessed via this link (https://rosie.graylab.jhu.edu). [ABSTRACT FROM AUTHOR]

LTR-retrotransposons (LTR-RTs) are a class of RNA-replicating transposon elements (TEs) that can alter genome structure and function by moving positions, repositioning genes, shifting exons, and causing chromosomal rearrangements. LTR-RTs are widespread in many plant genomes and constitute a significant portion of the genome. Their movement and activity in eukaryotic genomes can provide insight into genome evolution and gene function, especially when LTR-RTs are located near or within genes. Building the redundant and non-redundant LTR-RTs libraries and their annotations for species lacking this resource requires extensive bioinformatics pipelines and expensive computing power to analyze large amounts of genomic data. This increases the need for online services that provide computational resources with minimal overhead and maximum efficiency. Here, we present MegaLTR as a web server and standalone pipeline that detects intact LTR-RTs at the whole-genome level and integrates multiple tools for structure-based, homologybased, and de novo identification, classification, annotation, insertion time determination, and LTR-RT gene chimera analysis. MegaLTR also provides statistical analysis and visualization with multiple tools and can be used to accelerate plant species discovery and assist breeding programs in their efforts to improve genomic resources. We hope that the development of online services such as MegaLTR, which can analyze large amounts of genomic data, will become increasingly important for the automated detection and annotation of LTR-RT elements.

An Internet of Things-based security system and OpenCV technology have been developed to improve the efficiency and ease of monitoring video footage from CCTV. The face detection process is carried out using the Haar Cascade method, while facial recognition is carried out using the Local Binary Pattern Histogram algorithm. The test results show that light intensity has a significant influence on system accuracy, but this system provides convenience in monitoring CCTV video in real-time through a webserver and improves security, especially in rooms by utilizing Internet of Things technology. The current facial recognition success rate is 72%. Therefore, for the subsequent development of the system, it is recommended to increase the success rate of facial recognition and also implement the File Transfer Protocol to ensure better and better system performance. [ABSTRACT FROM AUTHOR]

Bioinformatics has been playing a crucial role in the scientific progress to fight against the pandemic of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The advances in novel algorithms, mega data technology, artificial intelligence and deep learning assisted the development of novel bioinformatics tools to analyze daily increasing SARS-CoV-2 data in the past years. These tools were applied in genomic analyses, evolutionary tracking, epidemiological analyses, protein structure interpretation, studies in virus-host interaction and clinical performance. To promote the in-silico analysis in the future, we conducted a review which summarized the databases, web services and software applied in SARS-CoV-2 research. Those digital resources applied in SARS-CoV-2 research may also potentially contribute to the research in other coronavirus and non-coronavirus viruses.

Cancer is the leading cause of death worldwide, resulting in the mortality of more than 10 million people in 2020, according to Global Cancer Statistics 2020. A potential cancer therapy involves targeting the DNA repair process by inhibiting PARP-1. In this study, classification models were constructed using a non-redundant set of 2018 PARP-1 inhibitors. Briefly, compounds were described by 12 fingerprint types and built using the random forest algorithm concomitant with various sampling approaches. Results indicated that PubChem with an oversampling approach yielded the best performance, with a Matthews correlation coefficient > 0.7 while also affording interpretable molecular features. Moreover, feature importance, as determined from the Gini index, revealed that the aromatic/cyclic/heterocyclic moiety, nitrogen-containing fingerprints, and the ether/aldehyde/alcohol moiety were important for PARP-1 inhibition. Finally, our predictive model was deployed as a web application called PARP1pred and is publicly available at https://parp1pred.streamlitapp.com, allowing users to predict the biological activity of query compounds using their SMILES notation as the input. It is anticipated that the model described herein will aid in the discovery of effective PARP-1 inhibitors.

Esophageal cancer is the seventh most prevalent and the sixth most lethal cancer. Esophageal squamous cell carcinoma (ESCC) is one of the major esophageal cancer subtypes that accounts for 87 % of the total cases. However, its molecular mechanism remains unclear. Here, we present an integrated database for ESCC called ESCCdb, which includes a total of 56 datasets and published studies from the GEO, Xena or SRA databases and related publications. It helps users to explore a particular gene with multiple graphical and interactive views with one click. The results comprise expression changes across 20 datasets, copy number alterations in 11 datasets, somatic mutations from 12 papers, related drugs derived from DGIdb, related pathways, and gene correlations. ESCCdb enables directly cross-dataset comparison of a gene’s mutations, expressions and copy number changes in multiple datasets. This allows users to easily assess the alterations in ESCC. Furthermore, survival analysis, drug-gene relationships, and results from whole-genome CRISPR/Cas9 screening can help users determine the clinical relevance, derive functional inferences, and identify potential drugs. Notably, ESCCdb also enables the exploration of the correlation structure and identification of potential key regulators for a process. Finally, we identified 789 consistently differential expressed genes; we summarized recurrently mutated genes and genes affected by significant copy number alterations. These genes may be stable biomarkers or important players during ESCC development. ESCCdb fills the gap between massive omics data and users’ needs for integrated analysis and can promote basic and clinical ESCC research. The database is freely accessible at http://cailab.labshare.cn/ESCCdb.

An webserver should be maintained by its experienced administrator under the firm knowledge and conviction on vulnerability measures. General administrators of novice learn the vulnerabilities with public literatures to get knowledge while unlearnt people sometimes try by the Internet articles for its affordability. However, the configuration of vulnerability countermeasures can be represented structurally. Therefore, even novices should learn more efficiently by using a learning support system originally developed those structures with the elements of vulnerability countermeasures than by learning with the literature. The system asks questions based on the learner's understanding. In the experiment, learners were divided into two groups of studying by the literature and studying by the system. Through the experiment consisted of a pre-test, learning, and post-test, the average score indicates the advantage of the system while the literature-based study shows partially advantageous. The explanatory text and feedback for items that the learners could not answer correctly need to be revised. [ABSTRACT FROM AUTHOR]

Viruses with rapid replication and easy mutation can become resistant to antiviral drug treatment. With novel viral infections emerging, such as the recent COVID-19 pandemic, novel antiviral therapies are urgently needed. Antiviral proteins, such as interferon, have been used for treating chronic hepatitis C infections for decades. Natural-origin antimicrobial peptides, such as defensins, have also been identified as possessing antiviral activities, including direct antiviral effects and the ability to induce indirect immune responses to viruses. To promote the development of antiviral drugs, we constructed a data repository of antiviral peptides and proteins (DRAVP). The database provides general information, antiviral activity, structure information, physicochemical information, and literature information for peptides and proteins. Because most of the proteins and peptides lack experimentally determined structures, AlphaFold was used to predict each antiviral peptide's structure. A free website for users (http://dravp.cpu-bioinfor.org/ , accessed on 30 August 2022) was constructed to facilitate data retrieval and sequence analysis. Additionally, all the data can be accessed from the web interface. The DRAVP database aims to be a useful resource for developing antiviral drugs. [ABSTRACT FROM AUTHOR]

LoRa (Long-Range) has become the Deoxyribo Nucleic Acid (DNA) of the Internet of things (IoT) for equipping smart solutions. Home automation is responsible for providing a safe and stylish home. This paper proposes a capable architecture of home automation for both short-range and long-range utilizing multiple communication technologies, namely LoRaWAN, server-based LoRa gateway, and Bluetooth connectivity. This integrated system effectively controls distinct types of home appliances and keeps smart management among all the electronics components. A regular user can easily manage these unified systems by using an Android application. This paper also presents experimental data analysis. The results and discussion section provide a set of experiments like estimated transmission delay calculation for LoRa, Wi-Fi, and Bluetooth, a coverage area calculation for LoRa with RSSI and SNR values, and a System Usability Scale (SUS). The scheme has achieved a SUS score of 93%. However, the proposed architecture can be called an outright package for smart home and will be very workable, abuzz, and handy.

Cancer is the leading cause of death worldwide, resulting in the mortality of more than 10 million people in 2020, according to Global Cancer Statistics 2020. A potential cancer therapy involves targeting the DNA repair process by inhibiting PARP-1. In this study, classification models were constructed using a non-redundant set of 2018 PARP-1 inhibitors. Briefly, compounds were described by 12 fingerprint types and built using the random forest algorithm concomitant with various sampling approaches. Results indicated that PubChem with an oversampling approach yielded the best performance, with a Matthews correlation coefficient > 0.7 while also affording interpretable molecular features. Moreover, feature importance, as determined from the Gini index, revealed that the aromatic/cyclic/heterocyclic moiety, nitrogen-containing fingerprints, and the ether/aldehyde/alcohol moiety were important for PARP-1 inhibition. Finally, our predictive model was deployed as a web application called PARP1pred and is publicly available at https://parp1pred.streamlitapp.com, allowing users to predict the biological activity of query compounds using their SMILES notation as the input. It is anticipated that the model described herein will aid in the discovery of effective PARP-1 inhibitors. [ABSTRACT FROM AUTHOR]

The lymphocyte-specific protein tyrosine kinase (LCK) is a critical target in leukemia treatment. However, potential off-target interactions involving LCK can lead to unintended consequences. This underscores the importance of accurately predicting the inhibitory reactions of drug molecules with LCK during the research and development stage. To address this, we introduce an advanced ensemble machine learning technique designed to estimate the binding affinity between molecules and LCK. This comprehensive method includes the generation and selection of molecular fingerprints, the design of the machine learning model, hyperparameter tuning, and a model ensemble. Through rigorous optimization, the predictive capabilities of our model have been significantly enhanced, raising test R2 values from 0.644 to 0.730 and reducing test RMSE values from 0.841 to 0.732. Utilizing these advancements, our refined ensemble model was employed to screen an MCE -like drug library. Through screening, we selected the top ten scoring compounds, and tested them using the ADP-Glo bioactivity assay. Subsequently, we employed molecular docking techniques to further validate the binding mode analysis of these compounds with LCK. The exceptional predictive accuracy of our model in identifying LCK inhibitors not only emphasizes its effectiveness in projecting LCK-related safety panel predictions but also in discovering new LCK inhibitors. For added user convenience, we have also established a webserver, and a GitHub repository to share the project.

Single-cell transcriptomics offers opportunities to investigate ligand-receptor (LR) interactions between heterogeneous cell populations within tissues. However, most existing tools for the inference of intercellular communication do not allow prioritization of functional LR associations that provoke certain biological responses in the receiver cells. In addition, current tools do not enable the identification of the impact on the downstream cell types of the receiver cells. We present CommPath, an open-source R package and webserver, to analyze and visualize the LR interactions and pathway-mediated intercellular communication chain with single-cell transcriptomic data. CommPath curates a comprehensive signaling pathway database to interpret the consequences of LR associations and therefore infers functional LR interactions. Furthermore, CommPath determines cell-cell communication chain by considering both the upstream and downstream cells of user-defined cell populations. Applying CommPath to human hepatocellular carcinoma dataset shows its ability to decipher complex LR interaction patterns and the associated intercellular communication chain, as well as their changes in disease versus homeostasis.

IntroductionAntibody-mediated immunity is an essential part of the immune system in vertebrates. The ability to specifically bind to antigens allows antibodies to be widely used in the therapy of cancers and other critical diseases. A key step in antibody therapeutics is the experimental identification of antibody-antigen interactions, which is generally time-consuming, costly, and laborious. Although some computational methods have been proposed to screen potential antibodies, the dependence on 3D structures still limits the application of these methods.MethodsHere, we developed a deep learning-assisted prediction method (i.e., AbAgIntPre) for fast identification of antibody-antigen interactions that only relies on amino acid sequences. A Siamese-like convolutional neural network architecture was established with the amino acid composition encoding scheme for both antigens and antibodies.Results and DiscussionThe generic model of AbAgIntPre achieved satisfactory performance with the Area Under Curve (AUC) of 0.82 on a high-quality generic independent test dataset. Besides, this approach also showed competitive performance on the more specific SARS-CoV dataset. We expect that AbAgIntPre can serve as an important complement to traditional experimental methods for antibody screening and effectively reduce the workload of antibody design. The web server of AbAgIntPre is freely available at http://www.zzdlab.com/AbAgIntPre.

Abstract DNA‐based biological ingredient identification and downstream pharmacology network analysis are commonly used in research for Traditional Chinese Medicine preparations (TCM formulas). Advancements in bioinformatics tools and the accumulation of related data have become driving forces for progress in this field. However, a lack of a platform integrating biological ingredient identification and downstream pharmacology network analysis hinders the deep understanding of TCM. In this study, we developed the TCM‐Suite platform composed of two sub‐databases, Holmes‐Suite and Watson‐Suite, for TCM biological ingredient identification and network pharmacology investigation, respectively, both are among the most complete: In the Holmes‐Suite, we collected and processed six types of marker gene sequences, accounting for 1,251,548 marker gene sequences. In the Watson‐Suite, we curated and integrated a massive number of entries from more than 10 public databases. Importantly, we developed a comprehensive pipeline to integrate TCM biological ingredient identification and downstream network pharmacology research, allowing users to simultaneously identify components of a TCM formula and analyze its potential pharmacology mechanism. Furthermore, we designed search engines and a user‐friendly platform to better search and visualize these rich resources. TCM‐Suite is a comprehensive and holistic platform for TCM‐based drug discovery and repurposing. TCM‐Suite website: http://TCM-Suite.AImicrobiome.cn.

MicroRNAs are key components of cellular regulatory networks, and breakdown in miRNA function causes cascading effects leading to pathophenotypes. A better understanding of the role of miRNAs in diseases is essential for human health. Here, we have devised a method for comprehensively mapping the associations between miRNAs and diseases by merging on a common key between two curated omics databases. The resulting bidirectional resource, miR2Trait, is more detailed than earlier catalogs, uncovers new relationships, and includes analytical utilities to interrogate and extract knowledge from these datasets. miR2Trait provides resources to compute the disease enrichment of a user-given set of miRNAs and analyze the miRNA profile of a specified diseasome. Reproducible examples demonstrating use-cases for each of these resource components are illustrated. Furthermore we used these tools to construct pairwise miRNA-miRNA and disease-disease enrichment networks, and identified 23 central miRNAs that could underlie major regulatory functions in the human genome. miR2Trait is available as an open-source command-line interface in Python3 (URL: https://github.com/miR2Trait) with a companion wiki documenting the scripts and data resources developed, under MIT license for commercial and noncommercial use. A minimal web-based implementation has been made available at https://sas.sastra.edu/pymir18. Supplementary information is available at: https://doi. org/10.6084/m9.figshare.8288825.v3. [ABSTRACT FROM AUTHOR]

Predicting the native or near-native binding pose of a small molecule within a protein binding pocket is an extremely important task in structure-based drug design, especially in the hit-to-lead and lead optimization phases. In this study, fastDRH, a free and open accessed web server, was developed to predict and analyze protein–ligand complex structures. In fastDRH server, AutoDock Vina and AutoDock-GPU docking engines, structure-truncated MM/PB(GB)SA free energy calculation procedures and multiple poses based per-residue energy decomposition analysis were well integrated into a user-friendly and multifunctional online platform. Benefit from the modular architecture, users can flexibly use one or more of three features, including molecular docking, docking pose rescoring and hotspot residue prediction, to obtain the key information clearly based on a result analysis panel supported by 3Dmol.js and Apache ECharts. In terms of protein–ligand binding mode prediction, the integrated structure-truncated MM/PB(GB)SA rescoring procedures exhibit a success rate of >80% in benchmark, which is much better than the AutoDock Vina (~70%). For hotspot residue identification, our multiple poses based per-residue energy decomposition analysis strategy is a more reliable solution than the one using only a single pose, and the performance of our solution has been experimentally validated in several drug discovery projects. To summarize, the fastDRH server is a useful tool for predicting the ligand binding mode and the hotspot residue of protein for ligand binding. The fastDRH server is accessible free of charge at http://cadd.zju.edu.cn/fastdrh/. [ABSTRACT FROM AUTHOR]

Astringency, a sensory experience causing mouth dryness, significantly impacts the taste of foods such as wine and tea, and astringent molecules may exhibit antibacterial properties. Traditional methods for predicting astringency are costly, and the connection between astringency and antibacterial activity remains largely unexplored. In this study, we present a pioneering computational approach that includes: (1) the creation of the first comprehensive astringency database comprising 238 molecules; (2) the development of a Ligand-Based Prediction (LBP) framework that combines large language models, deep learning, and traditional machine learning for enhanced molecular and peptide prediction; (3) an astringency predictor achieving 0.95 accuracy and 0.90 AUC, validated through electronic tongue measurements; (4) antibacterial predictors for molecules and peptides with accuracies of 0.92 and 0.88, respectively, revealing that 51 % of astringent molecules possess antibacterial properties; (5) accessibility of these predictors via the AstringentPD and ABPD web servers. This work not only enhances the understanding of taste-related molecules but also elucidates the relationship between astringency and antibacterial properties, setting the stage for future explorations in food science and medicinal applications., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Proportion of cancerous cells in a tumor sample, known as "tumor purity", is a major source of confounding factor in cancer data analyses. Lots of computational methods are available for estimating tumor purity from different types of genomics data or based on different platforms, which makes it difficult to compare and integrate the estimated results. To rectify the deviation caused by tumor purity effect, a number of methods for downstream data analysis have been developed, including tumor sample clustering, association study and differential methylation between tumor samples. However, using these computational tools remains a daunting task for many researchers since they require non-trivial computational skills. To this end, we present Purimeth, an integrated web-based tool for estimating and accounting for tumor purity in cancer DNA methylation studies. Purimeth implements three state-of-the-art methods for tumor purity estimation from DNA methylation array data: InfiniumPurify, MEpurity and PAMES. It also provides graphical interface for various analyses including differential methylation (DM), sample clustering, and purification of tumor methylomes, all with the consideration of tumor purities. In addition, Purimeth catalogs estimated tumor purities for TCGA samples from nine methods for users to visualize and explore. In conclusion, Purimeth provides an easy-operated way for researchers to explore tumor purity and implement cancer methylation data analysis. It is developed using Shiny (Version 1.6.0) and freely available at http://purimeth.comp-epi.com/.

MicroRNAs are key components of cellular regulatory networks, and breakdown in miRNA function causes cascading effects leading to pathophenotypes. A better understanding of the role of miRNAs in diseases is essential for human health. Here, we have devised a method for comprehensively mapping the associations between miRNAs and diseases by merging on a common key between two curated omics databases. The resulting bidirectional resource, miR2Trait, is more detailed than earlier catalogs, uncovers new relationships, and includes analytical utilities to interrogate and extract knowledge from these datasets. miR2Trait provides resources to compute the disease enrichment of a user-given set of miRNAs and analyze the miRNA profile of a specified diseasome. Reproducible examples demonstrating use-cases for each of these resource components are illustrated. Furthermore we used these tools to construct pairwise miRNA-miRNA and disease-disease enrichment networks, and identified 23 central miRNAs that could underlie major regulatory functions in the human genome. miR2Trait is available as an open-source command-line interface in Python3 (URL: https://github.com/miR2Trait) with a companion wiki documenting the scripts and data resources developed, under MIT license for commercial and non-commercial use. A minimal web-based implementation has been made available at https://sas.sastra.edu/pymir18. Supplementary information is available at: https://doi.org/10.6084/m9.figshare.8288825.v3.