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.

BACKGROUND: Nowadays, many public repositories containing large microarray gene expression datasets are available. However, the problem lies in the fact that microarray technology are less powerful and accurate than more recent Next Generation Sequencing technologies, such as RNA-Seq. In any case, information from microarrays is truthful and robust, thus it can be exploited through the integration of microarray data with RNA-Seq data. Additionally, information extraction and acquisition of large number of samples in RNA-Seq still entails very high costs in terms of time and computational resources.This paper proposes a new model to find the gene signature of breast cancer cell lines through the integration of heterogeneous data from different breast cancer datasets, obtained from microarray and RNA-Seq technologies. Consequently, data integration is expected to provide a more robust statistical significance to the results obtained. Finally, a classification method is proposed in order to test the robustness of the Differentially Expressed Genes when unseen data is presented for diagnosis. RESULTS: The proposed data integration allows analyzing gene expression samples coming from different technologies. The most significant genes of the whole integrated data were obtained through the intersection of the three gene sets, corresponding to the identified expressed genes within the microarray data itself, within the RNA-Seq data itself, and within the integrated data from both technologies. This intersection reveals 98 possible technology-independent biomarkers. Two different heterogeneous datasets were distinguished for the classification tasks: a training dataset for gene expression identification and classifier validation, and a test dataset with unseen data for testing the classifier. Both of them achieved great classification accuracies, therefore confirming the validity of the obtained set of genes as possible biomarkers for breast cancer. Through a feature selection process, a final small subset made up by six genes was considered for breast cancer diagnosis. CONCLUSIONS: This work proposes a novel data integration stage in the traditional gene expression analysis pipeline through the combination of heterogeneous data from microarrays and RNA-Seq technologies. Available samples have been successfully classified using a subset of six genes obtained by a feature selection method. Consequently, a new classification and diagnosis tool was built and its performance was validated using previously unseen samples.

The electrocardiogram (ECG) is a noninvasive technique used to reflect underlying heart conditions by measuring the electrical activity of the heart, and nowadays it is possible with just a few derivation (with just only two), obtain important information in order than an expert can recognize abnormal heart rhythms (the heart rate is very fast, very slow, or irregular) or a heart attack (myocardial infarction), and if it was recent or some time ago. In this paper, several intelligent classifiers are developed, focusing on the problem of diagnosing cardiac diseases based on the electrocardiogram (ECG), or more precisely, on the differentiation of several arrhythmia using a large data set. We will study and imitate the ECG treatment methodologies and the features extracted from the electrocardiograms used by the researchers, which obtained the best results in the PhysioNet Challenge (www.physionet.org/). We will extract a great amount of features, partly those used by these researchers and some additional others we considered to be important for the distinction previously mentioned. A new method based on different paradigms of intelligent computation (such as extreme learning machine, support vector machine, decision trees, genetic algorithms and feature selection) will be used to select the most relevant characteristics and to obtain a classifier capable of autonomously distinguishing the different types arrhythmia from the ECG signal.

MOTIVATION: Multiple sequence alignments (MSAs) are widely used approaches in bioinformatics to carry out other tasks such as structure predictions, biological function analyses or phylogenetic modeling. However, current tools usually provide partially optimal alignments, as each one is focused on specific biological features. Thus, the same set of sequences can produce different alignments, above all when sequences are less similar. Consequently, researchers and biologists do not agree about which is the most suitable way to evaluate MSAs. Recent evaluations tend to use more complex scores including further biological features. Among them, 3D structures are increasingly being used to evaluate alignments. Because structures are more conserved in proteins than sequences, scores with structural information are better suited to evaluate more distant relationships between sequences. RESULTS: The proposed multiobjective algorithm, based on the non-dominated sorting genetic algorithm, aims to jointly optimize three objectives: STRIKE score, non-gaps percentage and totally conserved columns. It was significantly assessed on the BAliBASE benchmark according to the Kruskal-Wallis test (P < 0.01). This algorithm also outperforms other aligners, such as ClustalW, Multiple Sequence Alignment Genetic Algorithm (MSA-GA), PRRP, DIALIGN, Hidden Markov Model Training (HMMT), Pattern-Induced Multi-sequence Alignment (PIMA), MULTIALIGN, Sequence Alignment Genetic Algorithm (SAGA), PILEUP, Rubber Band Technique Genetic Algorithm (RBT-GA) and Vertical Decomposition Genetic Algorithm (VDGA), according to the Wilcoxon signed-rank test (P < 0.05), whereas it shows results not significantly different to 3D-COFFEE (P > 0.05) with the advantage of being able to use less structures. Structural information is included within the objective function to evaluate more accurately the obtained alignments. AVAILABILITY: The source code is available at http://www.ugr.es/~fortuno/MOSAStrE/MO-SAStrE.zip.

Spino Cerebellar Ataxia type 2 is an autosomal dominant cerebellar hereditary ataxia with the highest prevalence in Cuba. Typical symptoms in patients of SCA2 ataxia include modifications in latency, peak velocity, and deviation in visual saccadic movements. After applying some electro-oculography based tests to both healthy and SCA2 afflicted individuals, differences in saccade morphology were found, mainly for 60° of stimulus amplitude. In this work, independent component analysis (ICA) is used to decompose the pulse and step components for the control of saccadic ocular movements, finding significant differences in time and amplitude ratio of both components. The obtained results point out the validity of the proposed methodology in order to study the effects of ataxia SCA2 in the oculomotor system.

This paper reports the investigations and experimental procedures conducted for designing an automatic sleep classification tool basedconly in the features extracted with wavelets from EEG, EMG and EOG (electro encephalo-mio- and oculo-gram) signals, without any visual aid or context-based evaluation. Real data collected from infants was processed and classified by several traditional and bio-inspired heuristics. Preliminary results show that some methods are able to attain success rates close to 70% when compared to an expert neurologist. Although still not sufficient to implement a reliable sleep classifier, these are promising results that, together with an analysis via Self-Organizing Maps and ant-based clustering, may help to improve the feature extraction and contribute to a better representation of the different classes' characteristics.

This paper presents a new adaptive procedure for the linear and nonlinear separation of signals with nonuniform, symmetrical probability distributions, based on both simulated annealing and competitive learning methods by means of a neural network, considering the properties of the vectorial spaces of sources and mixtures, and using a multiple linearization in the mixture space. Moreover, the paper proposes the fusion of two important paradigms-genetic algorithms and the blind separation of sources in nonlinear mixtures. In nonlinear mixtures, optimization of the system parameters and, especially, the search for invertible functions is very difficult due to the existence of many local minima. The main characteristics of the methods are their simplicity and the rapid convergence experimentally validated by the separation of many kinds of signals, such as speech or biomedical data.

This paper presents a new adaptive procedure for the linear and non-linear separation of signals with non-uniform, symmetrical probability distributions, based on both simulated annealing (SA) and competitive learning (CL) methods by means of a neural network, considering the properties of the vectorial spaces of sources and mixtures, and using a multiple linearization in the mixture space. Also, the paper proposes the fusion of two important paradigms, genetic algorithms and the blind separation of sources (GABSS) in nonlinear mixtures. From experimental results, this paper demonstrates the possible benefits offered by GAs in combination with BSS, such as robustness against local minima, the parallel search for various solutions, and a high degree of flexibility in the evaluation function. The main characteristics of the method are its simplicity and the rapid convergence experimentally validated by the separation of many kinds of signals, with different probability density functions.

This paper proposes the fusion of two important paradigms, Genetic Algorithms and the Blind Separation of Sources in Nonlinear Mixtures (GABSS). Although the topic of BSS, by means of various techniques, including ICA, PCA, and neural networks, has been amply discussed in the literature, the possibility of using genetic algorithms has not been explored thus far. However, in Nonlinear Mixtures, optimization of the system parameters and, especially, the search for invertible functions is very difficult due to the existence of many local minima. From experimental results, this paper demonstrates the possible benefits offered by GAs in combination with BSS, such as robustness against local minima, the parallel search for various solutions, and a high degree of flexibility in the evaluation function.

We propose a framework for constructing and training a radial basis function (RBF) neural network. The structure of the gaussian functions is modified using a pseudo-gaussian function (PG) in which two scaling parameters sigma are introduced, which eliminates the symmetry restriction and provides the neurons in the hidden layer with greater flexibility with respect to function approximation. We propose a modified PG-BF (pseudo-gaussian basis function) network in which the regression weights are used to replace the constant weights in the output layer. For this purpose, a sequential learning algorithm is presented to adapt the structure of the network, in which it is possible to create a new hidden unit and also to detect and remove inactive units. A salient feature of the network systems is that the method used for calculating the overall output is the weighted average of the output associated with each receptive field. The superior performance of the proposed PG-BF system over the standard RBF are illustrated using the problem of short-term prediction of chaotic time series.