Graph Theory-Based Sequence Descriptors as Remote Homology Predictors.

Alignment-free (AF) methodologies have increased in popularity in the last decades as alternative tools to alignment-based (AB) algorithms for performing comparative sequence analyses. They have been especially useful to detect remote homologs within the twilight zone of highly diverse gene/protein families and superfamilies. The most popular alignment-free methodologies, as well as their applications to classification problems, have been described in previous reviews. Despite a new set of graph theory-derived sequence/structural descriptors that have been gaining relevance in the detection of remote homology, they have been omitted as AF predictors when the topic is addressed. Here, we first go over the most popular AF approaches used for detecting homology signals within the twilight zone and then bring out the state-of-the-art tools encoding graph theory-derived sequence/structure descriptors and their success for identifying remote homologs. We also highlight the tendency of integrating AF features/measures with the AB ones, either into the same prediction model or by assembling the predictions from different algorithms using voting/weighting strategies, for improving the detection of remote signals. Lastly, we briefly discuss the efforts made to scale up AB and AF features/measures for the comparison of multiple genomes and proteomes. Alongside the achieved experiences in remote homology detection by both the most popular AF tools and other less known ones, we provide our own using the graphical-numerical methodologies, MARCH-INSIDE, TI2BioP, and ProtDCal. We also present a new Python-based tool (SeqDivA) with a friendly graphical user interface (GUI) for delimiting the twilight zone by using several similar criteria.

Surveying alignment-free features for Ortholog detection in related yeast proteomes by using supervised big data classifiers.

BACKGROUND: The development of new ortholog detection algorithms and the improvement of existing ones are of major importance in functional genomics. We have previously introduced a successful supervised pairwise ortholog classification approach implemented in a big data platform that considered several pairwise protein features and the low ortholog pair ratios found between two annotated proteomes (Galpert, D et al., BioMed Research International, 2015). The supervised models were built and tested using a Saccharomycete yeast benchmark dataset proposed by Salichos and Rokas (2011). Despite several pairwise protein features being combined in a supervised big data approach; they all, to some extent were alignment-based features and the proposed algorithms were evaluated on a unique test set. Here, we aim to evaluate the impact of alignment-free features on the performance of supervised models implemented in the Spark big data platform for pairwise ortholog detection in several related yeast proteomes. RESULTS: The Spark Random Forest and Decision Trees with oversampling and undersampling techniques, and built with only alignment-based similarity measures or combined with several alignment-free pairwise protein features showed the highest classification performance for ortholog detection in three yeast proteome pairs. Although such supervised approaches outperformed traditional methods, there were no significant differences between the exclusive use of alignment-based similarity measures and their combination with alignment-free features, even within the twilight zone of the studied proteomes. Just when alignment-based and alignment-free features were combined in Spark Decision Trees with imbalance management, a higher success rate (98.71%) within the twilight zone could be achieved for a yeast proteome pair that underwent a whole genome duplication. The feature selection study showed that alignment-based features were top-ranked for the best classifiers while the runners-up were alignment-free features related to amino acid composition. CONCLUSIONS: The incorporation of alignment-free features in supervised big data models did not significantly improve ortholog detection in yeast proteomes regarding the classification qualities achieved with just alignment-based similarity measures. However, the similarity of their classification performance to that of traditional ortholog detection methods encourages the evaluation of other alignment-free protein pair descriptors in future research.

An Effective Big Data Supervised Imbalanced Classification Approach for Ortholog Detection in Related Yeast Species.

Orthology detection requires more effective scaling algorithms. In this paper, a set of gene pair features based on similarity measures (alignment scores, sequence length, gene membership to conserved regions, and physicochemical profiles) are combined in a supervised pairwise ortholog detection approach to improve effectiveness considering low ortholog ratios in relation to the possible pairwise comparison between two genomes. In this scenario, big data supervised classifiers managing imbalance between ortholog and nonortholog pair classes allow for an effective scaling solution built from two genomes and extended to other genome pairs. The supervised approach was compared with RBH, RSD, and OMA algorithms by using the following yeast genome pairs: Saccharomyces cerevisiae-Kluyveromyces lactis, Saccharomyces cerevisiae-Candida glabrata, and Saccharomyces cerevisiae-Schizosaccharomyces pombe as benchmark datasets. Because of the large amount of imbalanced data, the building and testing of the supervised model were only possible by using big data supervised classifiers managing imbalance. Evaluation metrics taking low ortholog ratios into account were applied. From the effectiveness perspective, MapReduce Random Oversampling combined with Spark SVM outperformed RBH, RSD, and OMA, probably because of the consideration of gene pair features beyond alignment similarities combined with the advances in big data supervised classification.