MLGO: phylogeny reconstruction and ancestral inference from gene-order data

Background The rapid accumulation of whole-genome data has renewed interest in the study of using gene-order data for phylogenetic analyses and ancestral reconstruction. Current software and web servers typically do not support duplication and loss events along with rearrangements. Results MLGOMLGO (Maximum Likelihood for Gene-Order Analysis) is a web tool for the reconstruction of phylogeny and/or ancestral genomes from gene-order data. MLGOMLGO is based on likelihood computation and shows advantages over existing methods in terms of accuracy, scalability and flexibility. Conclusions To the best of our knowledge, it is the first web tool for analysis of large-scale genomic changes including not only rearrangements but also gene insertions, deletions and duplications. The web tool is available from http://www.geneorder.org/server.php

Phylogenetic reconstruction from transpositions

Background Because of the advent of high-throughput sequencing and the consequent reduction in the cost of sequencing, many organisms have been completely sequenced and most of their genes identified. It thus has become possible to represent whole genomes as ordered lists of gene identifiers and to study the rearrangement of these entities through computational means. As a result, genome rearrangement data has attracted increasing attentions from both biologists and computer scientists as a new type of data for phylogenetic analysis. The main events of genome rearrangements include inversions, transpositions and transversions. To date, GRAPPA and MGR are the most accurate methods for rearrangement phylogeny, both assuming inversion as the only event. However, due to the complexity of computing transposition distance, it is very difficult to analyze datasets when transpositions are dominant. Results We extend GRAPPA to handle transpositions. The new method is named GRAPPA-TP, with two major extensions: a heuristic method to estimate transposition distance, and a new transposition median solver for three genomes. Although GRAPPA-TP uses a greedy approach to compute the transposition distance, it is very accurate when genomes are relatively close. The new GRAPPA-TP is available from http://phylo.cse.sc.edu/ Conclusion Our extensive testing using simulated datasets shows that GRAPPA-TP is very accurate in terms of ancestor genome inference and phylogenetic reconstruction. Simulation results also suggest that model match is critical in genome rearrangement analysis: it is not accurate to simulate transpositions with other events including inversions

MDA-SKF: Similarity Kernel Fusion for Accurately Discovering miRNA-Disease Association

Identifying accurate associations between miRNAs and diseases is beneficial for diagnosis and treatment of human diseases. It is especially important to develop an efficient method to detect the association between miRNA and disease. Traditional experimental method has high precision, but its process is complicated and time-consuming. Various computational methods have been developed to uncover potential associations based on an assumption that similar miRNAs are always related to similar diseases. In this paper, we propose an accurate method, MDA-SKF, to uncover potential miRNA-disease associations. We first extract three miRNA similarity kernels (miRNA functional similarity, miRNA sequence similarity, Hamming profile similarity for miRNA) and three disease similarity kernels (disease semantic similarity, disease functional similarity, Hamming profile similarity for disease) in two subspaces, respectively. Then, due to limitations that some initial information may be lost in the process and some noises may be exist in integrated similarity kernel, we propose a novel Similarity Kernel Fusion (SKF) method to integrate multiple similarity kernels. Finally, we utilize the Laplacian Regularized Least Squares (LapRLS) method on the integrated kernel to find potential associations. MDA-SKF is evaluated by three evaluation methods, including global leave-one-out cross validation (LOOCV) and local LOOCV and 5-fold cross validation (CV), and achieves AUCs of 0.9576, 0.8356, and 0.9557, respectively. Compared with existing seven methods, MDA-SKF has outstanding performance on global LOOCV and 5-fold. We also test case studies to further analyze the performance of MDA-SKF on 32 diseases. Furthermore, 3200 candidate associations are obtained and a majority of them can be confirmed. It demonstrates that MDA-SKF is an accurate and efficient computational tool for guiding traditional experiments

Multivariate Information Fusion With Fast Kernel Learning to Kernel Ridge Regression in Predicting LncRNA-Protein Interactions

Long non-coding RNAs (lncRNAs) constitute a large class of transcribed RNA molecules. They have a characteristic length of more than 200 nucleotides which do not encode proteins. They play an important role in regulating gene expression by interacting with the homologous RNA-binding proteins. Due to the laborious and time-consuming nature of wet experimental methods, more researchers should pay great attention to computational approaches for the prediction of lncRNA-protein interaction (LPI). An in-depth literature review in the state-of-the-art in silico investigations, leads to the conclusion that there is still room for improving the accuracy and velocity. This paper propose a novel method for identifying LPI by employing Kernel Ridge Regression, based on Fast Kernel Learning (LPI-FKLKRR). This approach, uses four distinct similarity measures for lncRNA and protein space, respectively. It is remarkable, that we extract Gene Ontology (GO) with proteins, in order to improve the quality of information in protein space. The process of heterogeneous kernels integration, applies Fast Kernel Learning (FastKL) to deal with weight optimization. The extrapolation model is obtained by gaining the ultimate prediction associations, after using Kernel Ridge Regression (KRR). Experimental outcomes show that the ability of modeling with LPI-FKLKRR has extraordinary performance compared with LPI prediction schemes. On benchmark dataset, it has been observed that the best Area Under Precision Recall Curve (AUPR) of 0.6950 is obtained by our proposed model LPI-FKLKRR, which outperforms the integrated LPLNP (AUPR: 0.4584), RWR (AUPR: 0.2827), CF (AUPR: 0.2357), LPIHN (AUPR: 0.2299), and LPBNI (AUPR: 0.3302). Also, combined with the experimental results of a case study on a novel dataset, it is anticipated that LPI-FKLKRR will be a useful tool for LPI prediction

Using Jackknife to Assess the Quality of Gene Order Phylogenies

Background In recent years, gene order data has attracted increasing attention from both biologists and computer scientists as a new type of data for phylogenetic analysis. If gene orders are viewed as one character with a large number of states, traditional bootstrap procedures cannot be applied. Researchers began to use a jackknife resampling method to assess the quality of gene order phylogenies. Results In this paper, we design and conduct a set of experiments to validate the performance of this jackknife procedure and provide discussions on how to conduct it properly. Our results show that jackknife is very useful to determine the confidence level of a phylogeny obtained from gene orders and a jackknife rate of 40% should be used. However, although a branch with support value of 85% can be trusted, low support branches require careful investigation before being discarded. Conclusions Our experiments show that jackknife is indeed necessary and useful for gene order data, yet some caution should be taken when the results are interpreted

Discovering Cancer Subtypes via an Accurate Fusion Strategy on Multiple Profile Data

Discovering cancer subtypes is useful for guiding clinical treatment of multiple cancers. Progressive profile technologies for tissue have accumulated diverse types of data. Based on these types of expression data, various computational methods have been proposed to predict cancer subtypes. It is crucial to study how to better integrate these multiple profiles of data. In this paper, we collect multiple profiles of data for five cancers on The Cancer Genome Atlas (TCGA). Then, we construct three similarity kernels for all patients of the same cancer by gene expression, miRNA expression and isoform expression data. We also propose a novel unsupervised multiple kernel fusion method, Similarity Kernel Fusion (SKF), in order to integrate three similarity kernels into one combined kernel. Finally, we make use of spectral clustering on the integrated kernel to predict cancer subtypes. In the experimental results, the P-values from the Cox regression model and survival curve analysis can be used to evaluate the performance of predicted subtypes on three datasets. Our kernel fusion method, SKF, has outstanding performance compared with single kernel and other multiple kernel fusion strategies. It demonstrates that our method can accurately identify more accurate subtypes on various kinds of cancers. Our cancer subtype prediction method can identify essential genes and biomarkers for disease diagnosis and prognosis, and we also discuss the possible side effects of therapies and treatment