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.

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.

Many clinical studies have revealed the high biological similarities existing among different skin pathological states. These similarities create difficulties in the efficient diagnosis of skin cancer, and encourage to study and design new intelligent clinical decision support systems. In this sense, gene expression analysis can help find differentially expressed genes (DEGs) simultaneously discerning multiple skin pathological states in a single test. The integration of multiple heterogeneous transcriptomic datasets requires different pipeline stages to be properly designed: from suitable batch merging and efficient biomarker selection to automated classification assessment. This article presents a novel approach addressing all these technical issues, with the intention of providing new sights about skin cancer diagnosis. Although new future efforts will have to be made in the search for better biomarkers recognizing specific skin pathological states, our study found a panel of 8 highly relevant multiclass DEGs for discerning up to 10 skin pathological states: 2 healthy skin conditions a priori, 2 cataloged precancerous skin diseases and 6 cancerous skin states. Their power of diagnosis over new samples was widely tested by previously well-trained classification models. Robust performance metrics such as overall and mean multiclass F1-score outperformed recognition rates of 94% and 80%, respectively. Clinicians should give special attention to highlighted multiclass DEGs that have high gene expression changes present among them, and understand their biological relationship to different skin pathological states.

Computer-Aided Diagnosis (CAD) represents a relevant instrument to automatically classify between patients with and without Alzheimer's Disease (AD) using several actual imaging techniques. This study analyzes the optimization of volumes of interest (VOIs) to extract three-dimensional (3D) textures from Magnetic Resonance Image (MRI) in order to diagnose AD, Mild Cognitive Impairment converter (MCIc), Mild Cognitive Impairment nonconverter (MCInc) and Normal subjects. A relevant feature of the proposed approach is the use of 3D features instead of traditional two-dimensional (2D) features, by using 3D discrete wavelet transform (3D-DWT) approach for performing feature extraction from T-1 weighted MRI. Due to the high number of coefficients when applying 3D-DWT to each of the VOIs, a feature selection algorithm based on mutual information is used, as is the minimum Redundancy Maximum Relevance (mRMR) algorithm. Region optimization has been performed in order to discover the most relevant regions (VOIs) in the brain with the use of Multi-Objective Genetic Algorithms, being one of the objectives to be optimize the accuracy of the system. The error index of the system is computed by the confusion matrix obtained by the multi-class support vector machine (SVM) classifier. Principal Component Analysis (PCA) is used with the purpose of reducing the number of features to the classifier. The cohort of subjects used in the study consisted of 296 different patients. A first group of 206 patients was used to optimize VOI selection and another group of 90 independent subjects (that did not belong to the first group) was used to test the solutions yielded by the genetic algorithm. The proposed methodology obtains excellent results in multi-class classification achieving accuracies of 94.4% and also extracting significant information on the location of the most relevant points of the brain. This suggests that the proposed method could aid in the research of other neurodegenerative diseases, improving the accuracy of the diagnosis and finding the most relevant regions of the brain associated with them.

There are currently several biological databases related to proteins depending on the information we are interested to extract. Therefore, since a heterogeneous set of features will be needed (domains, structures, ontology terms, etc), several quite different databases should be consulted. The handling of different databases can become difficult, as each database could provide a different nomenclature for the same proteins. Anyway, these databases usually provides some mapping tools in order to determine the correspondence among the different nomenclatures used for the same protein. The main goal of this paper is to provide a biological database including a huge amount of protein information in order to be used for different purposes in bioinformatics. This database will be designed as a flexible and extensible tool and it could be extended and updated when new proteins are annotated or the included ones are modified.

Smoothing b-splines constitute a powerful and popular methodology for performing nonparametric regression with high accuracy. It is well known that the placement of the knots in spline smoothing approximation has an important and considerable effect on the behavior of the final approximation. For this purpose, in this paper a novel methodology is presented for optimal placement and selections of knots, in order to approximate or fit curves to data, using smoothing splines. A new method based on improved clustering algorithm is used to optimally select a reduced number of knots for constructing the base of the b-spline, while ensuring the best accuracy.

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.

There are several dementias but Alzheimer's Disease (AD) is leading cause of dementia in the world. In this paper, a new methodology for classification of MR images is proposed, using a large data base (more than one thousand patient). We have two main objectives in this paper: a first one where a classification method is developed to classify MR images as either normal or with the Alzheimer's disease and a second which is the ambitious goal of this study, the identification and classification between normal subjects, MCI patients and AD patients. It is noteworthy that with this last study we could offer a tool to assist the early diagnosis of dementia.

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.