A deep learning LSTM-based approach for forecasting annual pollen curves: Olea and Urticaceae pollen types as a case study.

Airborne pollen can trigger allergic rhinitis and other respiratory diseases in the synthesised population, which makes it one of the most relevant biological contaminants. Therefore, implementing accurate forecast systems is a priority for public health. The current forecast models are generally useful, but they falter when long time series of data are managed. The emergence of new computational techniques such as the LSTM algorithms could constitute a significant improvement for the pollen risk assessment. In this study, several LSTM variants were applied to forecast monthly pollen integrals in Málaga (southern Spain) using meteorological variables as predictors. Olea and Urticaceae pollen types were modelled as proxies of different annual pollen curves, using data from the period 1992-2022. The aims of this study were to determine the LSTM variants with the highest accuracy when forecasting monthly pollen integrals as well as to compare their performance with the traditional pollen forecast methods. The results showed that the CNN-LSTM were the most accurate when forecasting the monthly pollen integrals for both pollen types. Moreover, the traditional forecast methods were outperformed by all the LSTM variants. These findings highlight the importance of implementing LSTM models in pollen forecasting for public health and research applications.

Exploring IoT Vulnerabilities in a Comprehensive Remote Cybersecurity Laboratory.

With the rapid proliferation of Internet of things (IoT) devices across various sectors, ensuring robust cybersecurity practices has become paramount. The complexity and diversity of IoT ecosystems pose unique security challenges that traditional educational approaches often fail to address comprehensively. Current curricula may provide theoretical knowledge but typically lack the practical components necessary for students to engage with real-world cybersecurity scenarios. This gap hinders the development of proficient cybersecurity professionals capable of securing complex IoT infrastructures. To bridge this educational divide, a remote online laboratory was developed, allowing students to gain hands-on experience in identifying and mitigating cybersecurity threats in an IoT context. This virtual environment simulates real IoT ecosystems, enabling students to interact with actual devices and protocols while practicing various security techniques. The laboratory is designed to be accessible, scalable, and versatile, offering a range of modules from basic protocol analysis to advanced threat management. The implementation of this remote laboratory demonstrated significant benefits, equipping students with the necessary skills to confront and resolve IoT security issues effectively. Our results show an improvement in practical cybersecurity abilities among students, highlighting the laboratory's efficacy in enhancing IoT security education.

Ensemble-based genetic algorithm explainer with automized image segmentation: A case study on melanoma detection dataset.

Explainable Artificial Intelligence (XAI) makes AI understandable to the human user particularly when the model is complex and opaque. Local Interpretable Model-agnostic Explanations (LIME) has an image explainer package that is used to explain deep learning models. The image explainer of LIME needs some parameters to be manually tuned by the expert in advance, including the number of top features to be seen and the number of superpixels in the segmented input image. This parameter tuning is a time-consuming task. Hence, with the aim of developing an image explainer that automizes image segmentation, this paper proposes Ensemble-based Genetic Algorithm Explainer (EGAE) for melanoma cancer detection that automatically detects and presents the informative sections of the image to the user. EGAE has three phases. First, the sparsity of chromosomes in GAs is determined heuristically. Then, multiple GAs are executed consecutively. However, the difference between these GAs are in different number of superpixels in the input image that result in different chromosome lengths. Finally, the results of GAs are ensembled using consensus and majority votings. This paper also introduces how Euclidean distance can be used to calculate the distance between the actual explanation (delineated by experts) and the calculated explanation (computed by the explainer) for accuracy measurement. Experimental results on a melanoma dataset show that EGAE automatically detects informative lesions, and it also improves the accuracy of explanation in comparison with LIME efficiently. The python codes for EGAE, the ground truths delineated by clinicians, and the melanoma detection dataset are available at https://github.com/KhaosResearch/EGAE.

SALON ontology for the formal description of sequence alignments.

BACKGROUND: Information provided by high-throughput sequencing platforms allows the collection of content-rich data about biological sequences and their context. Sequence alignment is a bioinformatics approach to identifying regions of similarity in DNA, RNA, or protein sequences. However, there is no consensus about the specific common terminology and representation for sequence alignments. Thus, automatically linking the wide existing knowledge about the sequences with the alignments is challenging. RESULTS: The Sequence Alignment Ontology (SALON) defines a helpful vocabulary for representing and semantically annotating pairwise and multiple sequence alignments. SALON is an OWL 2 ontology that supports automated reasoning for alignments validation and retrieving complementary information from public databases under the Open Linked Data approach. This will reduce the effort needed by scientists to interpret the sequence alignment results. CONCLUSIONS: SALON defines a full range of controlled terminology in the domain of sequence alignments. It can be used as a mediated schema to integrate data from different sources and validate acquired knowledge.

GENECI: A novel evolutionary machine learning consensus-based approach for the inference of gene regulatory networks.

Gene regulatory networks define the interactions between DNA products and other substances in cells. Increasing knowledge of these networks improves the level of detail with which the processes that trigger different diseases are described and fosters the development of new therapeutic targets. These networks are usually represented by graphs, and the primary sources for their correct construction are usually time series from differential expression data. The inference of networks from this data type has been approached differently in the literature. Mostly, computational learning techniques have been implemented, which have finally shown some specialization in specific datasets. For this reason, the need arises to create new and more robust strategies for reaching a consensus based on previous results to gain a particular capacity for generalization. This paper presents GENECI (GEne NEtwork Consensus Inference), an evolutionary machine learning approach that acts as an organizer for constructing ensembles to process the results of the main inference techniques reported in the literature and to optimize the consensus network derived from them, according to their confidence levels and topological characteristics. After its design, the proposal was confronted with datasets collected from academic benchmarks (DREAM challenges and IRMA network) to quantify its accuracy. Subsequently, it was applied to a real-world biological network of melanoma patients whose results could be contrasted with medical research collected in the literature. Finally, it has been proved that its ability to optimize the consensus of several networks leads to outstanding robustness and accuracy, gaining a certain generalization capacity after facing the inference of multiple datasets. The source code is hosted in a public repository at GitHub under MIT license: https://github.com/AdrianSeguraOrtiz/GENECI. Moreover, to facilitate its installation and use, the software associated with this implementation has been encapsulated in a python package available at PyPI: https://pypi.org/project/geneci/.

Genes Involved in Immune Reinduction May Constitute Biomarkers of Response for Metastatic Melanoma Patients Treated with Targeted Therapy.

Targeted therapy in metastatic melanoma often achieves a major tumour regression response and significant long-term survival via the release of antigens that reinduce immunocompetence. The biomarkers thus activated may guide the prediction of response, but this association and its mechanism have yet to be established. Blood samples were collected from nineteen consecutive patients with metastatic melanoma before, during, and after treatment with targeted therapy. Differential gene expression analysis was performed, which identified the genes involved in the treatment, both in the first evaluation of response and during progression. Although clinical characteristics of the patients were poorer than those obtained in pivotal studies, radiological responses were similar to those reported previously (objective response rate: 73.7%). In the first tumour assessment, the expression of some genes increased (CXCL-10, SERPING1, PDL1, and PDL2), while that of others decreased (ARG1, IL18R1, IL18RAP, IL1R1, ILR2, FLT3, SLC11A1, CD163, and S100A12). The analysis of gene expression in blood shows that some are activated and others inhibited by targeted therapy. This response pattern may provide biomarkers of the immune reinduction response, which could be used to study potential combination treatments. Nevertheless, further studies are needed to validate these results.

Prediction of Anti-Glioblastoma Drug-Decorated Nanoparticle Delivery Systems Using Molecular Descriptors and Machine Learning.

The theoretical prediction of drug-decorated nanoparticles (DDNPs) has become a very important task in medical applications. For the current paper, Perturbation Theory Machine Learning (PTML) models were built to predict the probability of different pairs of drugs and nanoparticles creating DDNP complexes with anti-glioblastoma activity. PTML models use the perturbations of molecular descriptors of drugs and nanoparticles as inputs in experimental conditions. The raw dataset was obtained by mixing the nanoparticle experimental data with drug assays from the ChEMBL database. Ten types of machine learning methods have been tested. Only 41 features have been selected for 855,129 drug-nanoparticle complexes. The best model was obtained with the Bagging classifier, an ensemble meta-estimator based on 20 decision trees, with an area under the receiver operating characteristic curve (AUROC) of 0.96, and an accuracy of 87% (test subset). This model could be useful for the virtual screening of nanoparticle-drug complexes in glioblastoma. All the calculations can be reproduced with the datasets and python scripts, which are freely available as a GitHub repository from authors.

FIMED: Flexible management of biomedical data.

BACKGROUND AND OBJECTIVES: In the last decade, clinical trial management systems have become an essential support tool for data management and analysis in clinical research. However, these clinical tools have design limitations, since they are currently not able to cover the needs of adaptation to the continuous changes in the practice of the trials due to the heterogeneous and dynamic nature of the clinical research data. These systems are usually proprietary solutions provided by vendors for specific tasks. In this work, we propose FIMED, a software solution for the flexible management of clinical data from multiple trials, moving towards personalized medicine, which can contribute positively by improving clinical researchers quality and ease in clinical trials. METHODS: This tool allows a dynamic and incremental design of patients' profiles in the context of clinical trials, providing a flexible user interface that hides the complexity of using databases. Clinical researchers will be able to define personalized data schemas according to their needs and clinical study specifications. Thus, FIMED allows the incorporation of separate clinical data analysis from multiple trials. RESULTS: The efficiency of the software has been demonstrated by a real-world use case for a clinical assay in Melanoma disease, which has been indeed anonymized to provide a user demonstration. FIMED currently provides three data analysis and visualization components, guaranteeing a clinical exploration for gene expression data: heatmap visualization, clusterheatmap visualization, as well as gene regulatory network inference and visualization. An instance of this tool is freely available on the web at https://khaos.uma.es/fimed. It can be accessed with a demo user account, "researcher", using the password "demo". CONCLUSION: This paper shows FIMED as a flexible and user-friendly way of managing multidimensional clinical research data. Hence, without loss of generality, FIMED is flexible enough to be used in the context of any other disease where clinical data and assays are involved.

VIGLA-M: visual gene expression data analytics.

BACKGROUND: The analysis of gene expression levels is used in many clinical studies to know how patients evolve or to find new genetic biomarkers that could help in clinical decision making. However, the techniques and software available for these analyses are not intended for physicians, but for geneticists. However, enabling physicians to make initial discoveries on these data would benefit in the clinical assay development. RESULTS: Melanoma is a highly immunogenic tumor. Therefore, in recent years physicians have incorporated immune system altering drugs into their therapeutic arsenal against this disease, revolutionizing the treatment of patients with an advanced stage of the cancer. This has led us to explore and deepen our knowledge of the immunology surrounding melanoma, in order to optimize the approach. Within this project we have developed a database for collecting relevant clinical information for melanoma patients, including the storage of patient gene expression levels obtained from the NanoString platform (several samples are taken from each patient). The Immune Profiling Panel is used in this case. This database is being exploited through the analysis of the different expression profiles of the patients. This analysis is being done with Python, and a parallel version of the algorithms is available with Apache Spark to provide scalability as needed. CONCLUSIONS: VIGLA-M, the visual analysis tool for gene expression levels in melanoma patients is available at http://khaos.uma.es/melanoma/ . The platform with real clinical data can be accessed with a demo user account, physician, using password physician_test_7634 (if you encounter any problems, contact us at this email address: mailto: khaos@lcc.uma.es). The initial results of the analysis of gene expression levels using these tools are providing first insights into the patients' evolution. These results are promising, but larger scale tests must be developed once new patients have been sequenced, to discover new genetic biomarkers.

Surgical hand antisepsis: experimental study.

PURPOSE: Nosocomial infections account for one of the most serious complications in hospitalized patients around the world. Surgical site infections have significant economic implications, and surgical antisepsis plays an important role in such processes. METHODS: With prior approval by the Institutional Review Board and informed consent, 10 volunteers were randomly assigned to 3 protocols on hand antisepsis: protocol A (chloroxylenol 3%), protocol B (benzalkonium chloride at 1%), and protocol C (ethyl alcohol 61%, 1% chlorhexidine gluconate). Smears from both hands were cultured after each hand pro tocol (t0) and at the end of suturing (t1). Colony forming units were counted (CFUs on blood agar dishes) with digital counting software (Open CFU). Friedman test was used to compare the mean values among the groups, and a Bonferroni correction was made to determine the dissimilar group, with a P = 0.015. RESULTS: At t0 for protocol A the CFU count was 82.8 ± 1.3; protocol B was 9.7 ± 30; protocol C was 0.1 ± 0.3 (P < 0.001). At t1 for protocol A the CFU was 80.7 ± 89.4; protocol B was 7.5 ± 32; protocol C was 0.0 ± 0.0 (P < 0.001). No adverse events were present among the subjects. CONCLUSION: Ethyl alcohol at 61% with 1% chlorhexidine gluconate showed higher efficacy than the traditional washing antiseptics.

Biological Web Service Repositories Review.

Web services play a key role in bioinformatics enabling the integration of database access and analysis of algorithms. However, Web service repositories do not usually publish information on the changes made to their registered Web services. Dynamism is directly related to the changes in the repositories (services registered or unregistered) and at service level (annotation changes). Thus, users, software clients or workflow based approaches lack enough relevant information to decide when they should review or re-execute a Web service or workflow to get updated or improved results. The dynamism of the repository could be a measure for workflow developers to re-check service availability and annotation changes in the services of interest to them. This paper presents a review on the most well-known Web service repositories in the life sciences including an analysis of their dynamism. Freshness is introduced in this paper, and has been used as the measure for the dynamism of these repositories.

ReprOlive: a database with linked data for the olive tree (Olea europaea L.) reproductive transcriptome.

Plant reproductive transcriptomes have been analyzed in different species due to the agronomical and biotechnological importance of plant reproduction. Here we presented an olive tree reproductive transcriptome database with samples from pollen and pistil at different developmental stages, and leaf and root as control vegetative tissues http://reprolive.eez.csic.es). It was developed from 2,077,309 raw reads to 1,549 Sanger sequences. Using a pre-defined workflow based on open-source tools, sequences were pre-processed, assembled, mapped, and annotated with expression data, descriptions, GO terms, InterPro signatures, EC numbers, KEGG pathways, ORFs, and SSRs. Tentative transcripts (TTs) were also annotated with the corresponding orthologs in Arabidopsis thaliana from TAIR and RefSeq databases to enable Linked Data integration. It results in a reproductive transcriptome comprising 72,846 contigs with average length of 686 bp, of which 63,965 (87.8%) included at least one functional annotation, and 55,356 (75.9%) had an ortholog. A minimum of 23,568 different TTs was identified and 5,835 of them contain a complete ORF. The representative reproductive transcriptome can be reduced to 28,972 TTs for further gene expression studies. Partial transcriptomes from pollen, pistil, and vegetative tissues as control were also constructed. ReprOlive provides free access and download capability to these results. Retrieval mechanisms for sequences and transcript annotations are provided. Graphical localization of annotated enzymes into KEGG pathways is also possible. Finally, ReprOlive has included a semantic conceptualisation by means of a Resource Description Framework (RDF) allowing a Linked Data search for extracting the most updated information related to enzymes, interactions, allergens, structures, and reactive oxygen species.

kpath: integration of metabolic pathway linked data.

In the last few years, the Life Sciences domain has experienced a rapid growth in the amount of available biological databases. The heterogeneity of these databases makes data integration a challenging issue. Some integration challenges are locating resources, relationships, data formats, synonyms or ambiguity. The Linked Data approach partially solves the heterogeneity problems by introducing a uniform data representation model. Linked Data refers to a set of best practices for publishing and connecting structured data on the Web. This article introduces kpath, a database that integrates information related to metabolic pathways. kpath also provides a navigational interface that enables not only the browsing, but also the deep use of the integrated data to build metabolic networks based on existing disperse knowledge. This user interface has been used to showcase relationships that can be inferred from the information available in several public databases.

Sharing and executing linked data queries in a collaborative environment.

MOTIVATION: Life Sciences have emerged as a key domain in the Linked Data community because of the diversity of data semantics and formats available through a great variety of databases and web technologies. Thus, it has been used as the perfect domain for applications in the web of data. Unfortunately, bioinformaticians are not exploiting the full potential of this already available technology, and experts in Life Sciences have real problems to discover, understand and devise how to take advantage of these interlinked (integrated) data. RESULTS: In this article, we present Bioqueries, a wiki-based portal that is aimed at community building around biological Linked Data. This tool has been designed to aid bioinformaticians in developing SPARQL queries to access biological databases exposed as Linked Data, and also to help biologists gain a deeper insight into the potential use of this technology. This public space offers several services and a collaborative infrastructure to stimulate the consumption of biological Linked Data and, therefore, contribute to implementing the benefits of the web of data in this domain. Bioqueries currently contains 215 query entries grouped by database and theme, 230 registered users and 44 end points that contain biological Resource Description Framework information. AVAILABILITY: The Bioqueries portal is freely accessible at http://bioqueries.uma.es. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Transparent mediation-based access to multiple yeast data sources using an ontology driven interface.

BACKGROUND: Saccharomyces cerevisiae is recognized as a model system representing a simple eukaryote whose genome can be easily manipulated. Information solicited by scientists on its biological entities (Proteins, Genes, RNAs...) is scattered within several data sources like SGD, Yeastract, CYGD-MIPS, BioGrid, PhosphoGrid, etc. Because of the heterogeneity of these sources, querying them separately and then manually combining the returned results is a complex and time-consuming task for biologists most of whom are not bioinformatics expert. It also reduces and limits the use that can be made on the available data. RESULTS: To provide transparent and simultaneous access to yeast sources, we have developed YeastMed: an XML and mediator-based system. In this paper, we present our approach in developing this system which takes advantage of SB-KOM to perform the query transformation needed and a set of Data Services to reach the integrated data sources. The system is composed of a set of modules that depend heavily on XML and Semantic Web technologies. User queries are expressed in terms of a domain ontology through a simple form-based web interface. CONCLUSIONS: YeastMed is the first mediation-based system specific for integrating yeast data sources. It was conceived mainly to help biologists to find simultaneously relevant data from multiple data sources. It has a biologist-friendly interface easy to use. The system is available at http://www.khaos.uma.es/yeastmed/.

Social pathway annotation: extensions of the systems biology metabolic modelling assistant.

High-throughput experiments have produced large amounts of heterogeneous data in the life sciences. These data are usually represented in different formats (and sometimes in technical documents) on the Web. Inevitably, life science researchers have to deal with all these data and different formats to perform their daily research, but it is simply not possible for a single human mind to analyse all these data. The integration of data in the life sciences is a key component in the analysis of biological processes. These data may contain errors, but the curation of the vast amount of data generated in the 'omic' era cannot be done by individual researchers. To address this problem, community-driven tools could be used to assist with data analysis. In this article, we focus on a tool with social networking capabilities built on top of the SBMM (Systems Biology Metabolic Modelling) Assistant to enable the collaborative improvement of metabolic pathway models (the application is freely available at http://sbmm.uma.es/SPA).

Protopia: a protein-protein interaction tool.

BACKGROUND: Protein-protein interactions can be considered the basic skeleton for living organism self-organization and homeostasis. Impressive quantities of experimental data are being obtained and computational tools are essential to integrate and to organize this information. This paper presents Protopia, a biological tool that offers a way of searching for proteins and their interactions in different Protein Interaction Web Databases, as a part of a multidisciplinary initiative of our institution for the integration of biological data http://asp.uma.es. RESULTS: The tool accesses the different Databases (at present, the free version of Transfac, DIP, Hprd, Int-Act and iHop), and results are expressed with biological protein names or databases codes and can be depicted as a vector or a matrix. They can be represented and handled interactively as an organic graph. Comparison among databases is carried out using the Uniprot codes annotated for each protein. CONCLUSION: The tool locates and integrates the current information stored in the aforementioned databases, and redundancies among them are detected. Results are compatible with the most important network analysers, so that they can be compared and analysed by other world-wide known tools and platforms. The visualization possibilities help to attain this goal and they are especially interesting for handling multiple-step or complex networks.

KA-SB: from data integration to large scale reasoning.

BACKGROUND: The analysis of information in the biological domain is usually focused on the analysis of data from single on-line data sources. Unfortunately, studying a biological process requires having access to disperse, heterogeneous, autonomous data sources. In this context, an analysis of the information is not possible without the integration of such data. METHODS: KA-SB is a querying and analysis system for final users based on combining a data integration solution with a reasoner. Thus, the tool has been created with a process divided into two steps: 1) KOMF, the Khaos Ontology-based Mediator Framework, is used to retrieve information from heterogeneous and distributed databases; 2) the integrated information is crystallized in a (persistent and high performance) reasoner (DBOWL). This information could be further analyzed later (by means of querying and reasoning). RESULTS: In this paper we present a novel system that combines the use of a mediation system with the reasoning capabilities of a large scale reasoner to provide a way of finding new knowledge and of analyzing the integrated information from different databases, which is retrieved as a set of ontology instances. This tool uses a graphical query interface to build user queries easily, which shows a graphical representation of the ontology and allows users o build queries by clicking on the ontology concepts. CONCLUSION: These kinds of systems (based on KOMF) will provide users with very large amounts of information (interpreted as ontology instances once retrieved), which cannot be managed using traditional main memory-based reasoners. We propose a process for creating persistent and scalable knowledgebases from sets of OWL instances obtained by integrating heterogeneous data sources with KOMF. This process has been applied to develop a demo tool http://khaos.uma.es/KA-SB, which uses the BioPax Level 3 ontology as the integration schema, and integrates UNIPROT, KEGG, CHEBI, BRENDA and SABIORK databases.

Systems biology metabolic modeling assistant: an ontology-based tool for the integration of metabolic data in kinetic modeling.

SUMMARY: We present Systems Biology Metabolic Modeling Assistant (SBMM Assistant), a tool built using an ontology-based mediator, and designed to facilitate metabolic modeling through the integration of data from repositories that contain valuable metabolic information. This software can be used for the visualization, design and management of metabolic networks; selection, integration and storage of metabolic information; and as an assistant for kinetic modeling. AVAILABILITY: SBMM Assistant for academic use is freely available at http://www.sbmm.uma.es.

AMMO-Prot: amine system project 3D-model finder.

BACKGROUND: Amines are biogenic amino acid derivatives, which play pleiotropic and very important yet complex roles in animal physiology. For many other relevant biomolecules, biochemical and molecular data are being accumulated, which need to be integrated in order to be effective in the advance of biological knowledge in the field. For this purpose, a multidisciplinary group has started an ontology-based system named the Amine System Project (ASP) for which amine-related information is the validation bench. RESULTS: In this paper, we describe the Ontology-Based Mediator developed in the Amine System Project (http://asp.uma.es) using the infrastructure of Semantic Directories, and how this system has been used to solve a case related to amine metabolism-related protein structures. CONCLUSIONS: This infrastructure is used to publish and manage not only ontologies and their relationships, but also metadata relating to the resources committed with the ontologies. The system developed is available at http://asp.uma.es/WebMediator.