MIGNON is a workflow for the analysis of RNA-Seq experiments, which not only efficiently manages the estimation of gene expression levels from raw sequencing reads, but also calls genomic variants present in the transcripts analyzed. Moreover, this is the first workflow that provides a framework for the integration of transcriptomic and genomic data based on a mechanistic model of signaling pathway activities that allows a detailed biological interpretation of the results, including a comprehensive functional profiling of cell activity. MIGNON covers the whole process, from reads to signaling circuit activity estimations, using state-of-the-art tools, it is easy to use and it is deployable in different computational environments, allowing an optimized use of the resources available.

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.

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.

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.

BACKGROUND: A popular query from scientists reading a biomedical abstract is to search for topic-related documents in bibliographic databases. Such a query is challenging because the amount of information attached to a single abstract is little, whereas classification-based retrieval algorithms are optimally trained with large sets of relevant documents. As a solution to this problem, we propose a query expansion method that extends the information related to a manuscript using its cited references. RESULTS: Data on cited references and text sections in 249,108 full-text biomedical articles was extracted from the Open Access subset of the PubMed Central® database (PMC-OA). Of the five standard sections of a scientific article, the Introduction and Discussion sections contained most of the citations (mean = 10.2 and 9.9 citations, respectively). A large proportion of articles (98.4%) and their cited references (79.5%) were indexed in the PubMed® database. Using the MedlineRanker abstract classification tool, cited references allowed accurate retrieval of the citing document in a test set of 10,000 documents and also of documents related to six biomedical topics defined by particular MeSH® terms from the entire PMC-OA (p-value<0.01). Classification performance was sensitive to the topic and also to the text sections from which the references were selected. Classifiers trained on the baseline (i.e., only text from the query document and not from the references) were outperformed in almost all the cases. Best performance was often obtained when using all cited references, though using the references from Introduction and Discussion sections led to similarly good results. This query expansion method performed significantly better than pseudo relevance feedback in 4 out of 6 topics. CONCLUSIONS: The retrieval of documents related to a single document can be significantly improved by using the references cited by this document (p-value<0.01). Using references from Introduction and Discussion performs almost as well as using all references, which might be useful for methods that require reduced datasets due to computational limitations. Cited references from particular sections might not be appropriate for all topics. Our method could be a better alternative to pseudo relevance feedback though it is limited by full text availability.

Multiple sequence alignment (MSA) is one of the most studied approach in Bioinformatics to carry out other outstanding tasks like structural predictions, biological function analysis or next-generation sequencing. However, MSA algorithms do not achieve consistent results in all cases, as alignments become difficult when sequences have low similarity. In other words, each algorithm is focused in specific features of sequences and their results depend on them. For this reason, each approach could align better those sections of sequences that include such features, obtaining partially optimal solutions. In this work, a multiobjective evolutionary algorithm based on NSGA-II will be implemented in order to assemble previously aligned sequences, trying to avoid suboptimal alignments.