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Abstract This Supplement issue, presents five research articles which are distributed, mainly due to the subject they address, from the 8th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2020), which was held on line, during September, 30th–2nd October, 2020. These contributions have been chosen because of their quality and the importance of their findings. Those contributions were then invited to participate in this supplement for the following journals of BMC: BMC Bioinformatics and BMC Genomics. In the present Editorial in BMC journal, we summarize the contributions that provide a clear overview of the thematic areas covered by the IWBBIO conference, ranging from theoretical/review aspects to real-world applications of bioinformatic and biomedical engineering.

The ITISE 2023 (9th International Conference on Time Series and Forecasting) sought to provide a discussion forum for scientists, engineers, educators and students about the latest ideas and realizations in the foundations, theory, models and applications for inter- disciplinary and multidisciplinary research encompassing the disciplines of computer science, mathematics, statistics, forecaster, econometric, etc [...]

Bioinformatics is revolutionizing Biomedicine in the way we treat and diagnose pathologies related to biological manifestations resulting from variations or mutations of our DNA [...]

The diagnosis of different pathologies and stages of cancer using whole histopathology slide images (WSI) is the gold standard for determining the degree of tissue metastasis. The use of deep learning systems in the field of medical images, especially histopathology images, is becoming increasingly important. The training and optimization of deep neural network models involve fine-tuning parameters and hyperparameters such as learning rate, batch size (BS), and boost to improve the performance of the model in task-specific applications. Tuning hyperparameters is a major challenge in designing deep neural network models, having a large impact on the performance. This paper analyzes how the parameters and hyperparameters of a deep learning architecture affect the classification of colorectal cancer (CRC) histopathology images using the well-known VGG19 model. This paper also discusses the pre-processing of these images, such as the use of color normalization and stretching transformations on the data set. Among these hyperparameters, the most important neural network hyperparameter is the learning rate (LR). In this paper, different strategies for the optimization of LR are analyzed (both static and dynamic) and a new experiment based on the variation of LR is proposed (the relevance of dynamic strategies over fixed LR is highlighted), after each layer of the neural network together with decreasing variations according to the epochs. The results obtained are very remarkable, obtaining in the simulation an accurate system that achieves 96.4% accuracy on test images (for nine different tissue classes) using the triangular-cyclic learning rate.

Abstract In the current supplement, we are proud to present seventeen relevant contributions from the 6th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2018), which was held during April 25-27, 2018 in Granada (Spain). These contributions have been chosen because of their quality and the importance of their findings.

Early diagnosis of cancer is very important as it significantly increases the chances of appropriate treatment and survival. To this end, Deep Learning models are increasingly used in the classification and segmentation of histopathological images, as they obtain high accuracy index and can help specialists. In most cases, images need to be preprocessed for these models to work correctly. In this paper, a comparative study of different preprocessing methods and deep learning models for a set of breast cancer images is presented. For this purpose, the statistical test ANOVA with data obtained from the performance of five different deep learning models is analyzed. An important conclusion from this test can be obtained; from the point of view of the accuracy of the system, the main repercussion is the deep learning models used, however, the filter used for the preprocessing of the image, has no statistical significance for the behavior of the system.

In this contribution, a novel methodology for multi-class classification in the field of Parkinson’s disease is proposed. The methodology is structured in two phases. In a first phase, the most relevant volumes of interest (VOI) of the brain are selected by means of an evolutionary multi-objective optimization (MOE) algorithm. Each of these VOIs are subjected to volumetric feature extraction using the Three-Dimensional Discrete Wavelet Transform (3D-DWT). When applying 3D-DWT, a high number of coefficients is obtained, requiring the use of feature selection/reduction algorithms to find the most relevant features. The method used in this contribution is based on Mutual Redundancy (MI) and Minimum Maximum Relevance (mRMR) and PCA. To optimize the VOI selection, a first group of 550 MRI was used for the 5 classes: PD, SWEDD, Prodromal, GeneCohort and Normal. Once the Pareto Front of the solutions is obtained (with varying degrees of complexity, reflected in the number of selected VOIs), these solutions are tested in a second phase. In order to analyze the SVM classifier accuracy, a test set of 367 MRI was used. The methodology obtains relevant results in multi-class classification, presenting several solutions with different levels of complexity and precision (Pareto Front solutions), reaching a result of 97% as the highest precision in the test data.

The coronavirus disease 2019 (COVID-19) has caused millions of deaths and one of the greatest health crises of all time. In this disease, one of the most important aspects is the early detection of the infection to avoid the spread. In addition to this, it is essential to know how the disease progresses in patients, to improve patient care. This contribution presents a novel method based on a hierarchical intelligent system, that analyzes the application of deep learning models to detect and classify patients with COVID-19 using both X-ray and chest computed tomography (CT). The methodology was divided into three phases, the first being the detection of whether or not a patient suffers from COVID-19, the second step being the evaluation of the percentage of infection of this disease and the final phase is to classify the patients according to their severity. Stratification of patients suffering from COVID-19 according to their severity using automatic systems based on machine learning on medical images (especially X-ray and CT of the lungs) provides a powerful tool to help medical experts in decision making. In this article, a new contribution is made to a stratification system with three severity levels (mild, moderate and severe) using a novel histogram database (which defines how the infection is in the different CT slices for a patient suffering from COVID-19). The first two phases use CNN Densenet-161 pre-trained models, and the last uses SVM with LDA supervised learning algorithms as classification models. The initial stage detects the presence of COVID-19 through X-ray multi-class (COVID-19 vs. No-Findings vs. Pneumonia) and the results obtained for accuracy, precision, recall, and F1-score values are 88%, 91%, 87%, and 89%, respectively. The following stage manifested the percentage of COVID-19 infection in the slices of the CT-scans for a patient and the results in the metrics evaluation are 0.95 in Pearson Correlation coefficient, 5.14 in MAE and 8.47 in RMSE. The last stage finally classifies a patient in three degrees of severity as a function of global infection of the lungs and the results achieved are 95% accurate.

In more recent years, a significant increase in the number of available biological experiments has taken place due to the widespread use of massive sequencing data. Furthermore, the continuous developments in the machine learning and in the high performance computing areas, are allowing a faster and more efficient analysis and processing of this type of data. However, biological information about a certain disease is normally widespread due to the use of different sequencing technologies and different manufacturers, in different experiments along the years around the world. Thus, nowadays it is of paramount importance to attain a correct integration of biologically-related data in order to achieve genuine benefits from them. For this purpose, this work presents an integration of multiple Microarray and RNA-seq platforms, which has led to the design of a multiclass study by collecting samples from the main four types of leukemia, quantified at gene expression. Subsequently, in order to find a set of differentially expressed genes with the highest discernment capability among different types of leukemia, an innovative parameter referred to as coverage is presented here. This parameter allows assessing the number of different pathologies that a certain gen is able to discern. It has been evaluated together with other widely known parameters under assessment of an ANOVA statistical test which corroborated its filtering power when the identified genes are subjected to a machine learning process at multiclass level. The optimal tuning of gene extraction evaluated parameters by means of this statistical test led to the selection of 42 highly relevant expressed genes. By the use of minimum-Redundancy Maximum-Relevance (mRMR) feature selection algorithm, these genes were reordered and assessed under the operation of four different classification techniques. Outstanding results were achieved by taking exclusively the first ten genes of the ranking into consideration. Finally, specific literature was consulted on this last subset of genes, revealing the occurrence of practically all of them with biological processes related to leukemia. At sight of these results, this study underlines the relevance of considering a new parameter which facilitates the identification of highly valid expressed genes for simultaneously discerning multiple types of leukemia.

Most of the research studies developed applying microarray technology to the characterization of different pathological states of any disease may fail in reaching statistically significant results. This is largely due to the small repertoire of analysed samples, and to the limitation in the number of states or pathologies usually addressed. Moreover, the influence of potential deviations on the gene expression quantification is usually disregarded. In spite of the continuous changes in omic sciences, reflected for instance in the emergence of new Next-Generation Sequencing-related technologies, the existing availability of a vast amount of gene expression microarray datasets should be properly exploited. Therefore, this work proposes a novel methodological approach involving the integration of several heterogeneous skin cancer series, and a later multiclass classifier design. This approach is thus a way to provide the clinicians with an intelligent diagnosis support tool based on the use of a robust set of selected biomarkers, which simultaneously distinguishes among different cancer-related skin states. To achieve this, a multi-platform combination of microarray datasets from Affymetrix and Illumina manufacturers was carried out. This integration is expected to strengthen the statistical robustness of the study as well as the finding of highly-reliable skin cancer biomarkers. Specifically, the designed operation pipeline has allowed the identification of a small subset of 17 differentially expressed genes (DEGs) from which to distinguish among 7 involved skin states. These genes were obtained from the assessment of a number of potential batch effects on the gene expression data. The biological interpretation of these genes was inspected in the specific literature to understand their underlying information in relation to skin cancer. Finally, in order to assess their possible effectiveness in cancer diagnosis, a cross-validation Support Vector Machines (SVM)-based classification including feature ranking was performed. The accuracy attained exceeded the 92% in overall recognition of the 7 different cancer-related skin states. The proposed integration scheme is expected to allow the co-integration with other state-of-the-art technologies such as RNA-seq.

Heart disease is currently one of the leading causes of death in developed countries. The electrocardiogram is an important source of information for identifying these conditions, therefore, becomes necessary to seek an advanced system of diagnosis based on these signals. In this paper we used samples of electrocardiograms of MIT-related database with ten types of pathologies and a rate corresponding to normal (healthy patient), which are processed and used for extraction from its two branches of a wide range of features. Next, various techniques have been applied to feature selection based on genetic algorithms, principal component analysis and mutual information. To carry out the task of intelligent classification, 3 different scenarios have been considered. These techniques allow us to achieve greater efficiency in the classification methods used, namely support vector machines (SVM) and decision trees (DT) to perform a comparative analysis between them. Finally, during the development of this contribution, the use of very non-invasive devices (2 channel ECG) was analyzed, we could practically classify them as wearable, which would not need interaction by the user, and whose energy consumption is very small to extend the average life of the user been on it.

The present work analyses the wireless sensor network protocol (DARP) and the impact of different configuration parameter sets on its performance. Different scenarios have been considered, in order to gain a better understanding of the influence of the configuration on network protocols. The developed statistical analysis is based on the method known as Analysis of Variance (ANOVA), which focuses on the effect of the configuration on the performance of DARP. Three main dependent variables were considered: number of control messages sent during the set-up time, energy consumption and convergence time. A total of 20,413 simulations were carried out to ensure greater robustness in the statistical conclusions. The main goal of this work is to discover the most critical configuration parameters for the protocol, with a view to potential applications in Smart City type scenarios.

In this paper, a temperature control in real time control process was presented using several control algorithms. A quantitative comparison based on the real power consumption and (the precision and the robustness) of these controllers during the same control process and under the same conditions will be done. The proposed Adaptive and Self Organizing Fuzzy policy has been able to prove its superiority against the remaining controllers. The new Adaptive and Self Organizing Fuzzy Logic Controller starts the control with a very limited information about the controlled process (delay and the monotonicity sign) and without any kind of offline pre-training, the adaptive controller acts online to collect the necessary background to adapt their rules consequents and to self organize their membership functions from the real behavior of the controlled process. During 200 minutes and under the same conditions all the performed controllers have been used to control the room temperature, each simulation has been repeated five times with two different sets of set points. These amounts of results was used as a set of sampling for the statistical tool ANOVA (Analysis of Variance) that can prove and illustrate the validity and the extrapolability of the conclusions extracted from several stages of this work.