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Motivation: Disease progression originates from the concept that an individual disease may go through different changes as it evolves, and such changes can cause new diseases. It is important to find a progression between diseases since knowing the prior-posterior relationship beforehand can prevent further complications or evolutions to other diseases. Furthermore, the series of progressions can be represented in the form of a chain, which enables us to readily infer successive influences from one disease to another after many passages through other diseases. Methods: In this paper, we propose a systematic approach for finding a disease progression chain from a source disease to a target one via exploring a disease network. The network is constructed based on various sets of biomedical data. To find the most influential progression chains, the k-shortest path search algorithm is employed. The most representative algorithms such as A*, Dijkstra, and Yen’s are incorporated into the proposed method. Results: A disease network consisting of 3,302 diseases was constructed based on four sources of biomedical data: disease-protein relations, biological pathways, clinical history, and biomedical literature information. The last three sets of data contain prior-posterior information, and they endow directionality on the edges of the network. The results were interesting and informative: for example, when colitis and respiratory insufficiency were set as a source disease and a target one, respectively, five progression chains were found within several seconds (when k = 5). Each chain was provided with a progression score, which indicates the strength of plausibility relative to others. Similarly, the proposed method can be expanded to any pair of source-target diseases in the network. This can be utilized as a preliminary tool for inferring complications or progressions between diseases. [ABSTRACT FROM AUTHOR]

High dimensional biomedical data contain tens of thousands of features, accurate and effective identification of the core features in these data can be used to assist diagnose related diseases. However, there are often a large number of irrelevant or redundant features in biomedical data, which seriously affect subsequent classification accuracy and machine learning efficiency. To solve this problem, a novel filter feature selection algorithm based on redundant removal (FSBRR) is proposed to classify high dimensional biomedical data in this paper. First of all, two redundant criteria are determined by vertical relevance (the relationship between feature and class attribute) and horizontal relevance (the relationship between feature and feature). Secondly, to quantify redundant criteria, an approximate redundancy feature framework based on mutual information (MI) is defined to remove redundant and irrelevant features. To evaluate the effectiveness of our proposed algorithm, controlled trials based on typical feature selection algorithm are conducted using three different classifiers, and the experimental results indicate that the FSBRR algorithm can effectively reduce the feature dimension and improve the classification accuracy. In addition, an experiment of small sample dataset is designed and conducted in the section of discussion and analysis to clarify the specific implementation process of FSBRR algorithm more clearly. [ABSTRACT FROM AUTHOR]

Feature selection and classification are the main topics in microarray data analysis. Although many feature selection methods have been proposed and developed in this field, SVM-RFE (Support Vector Machine based on Recursive Feature Elimination) is proved as one of the best feature selection methods, which ranks the features (genes) by training support vector machine classification model and selects key genes combining with recursive feature elimination strategy. The principal drawback of SVM-RFE is the huge time consumption. To overcome this limitation, we introduce a more efficient implementation of linear support vector machines and improve the recursive feature elimination strategy and then combine them together to select informative genes. Besides, we propose a simple resampling method to preprocess the datasets, which makes the information distribution of different kinds of samples balanced and the classification results more credible. Moreover, the applicability of four common classifiers is also studied in this paper. Extensive experiments are conducted on six most frequently used microarray datasets in this field, and the results show that the proposed methods have not only reduced the time consumption greatly but also obtained comparable classification performance. [ABSTRACT FROM AUTHOR]

Microarray technology is important to simultaneously express multiple genes over a number of time points. Multiple classifier models, such as sparse representation (SR)-based method, have been developed to classify microarray gene expression data. These methods allocate the gene data points to different clusters. In this paper, we propose a novel collaborative representation (CR)-based classification with regularized least square to classify gene data. First, the CR codes a testing sample as a sparse linear combination of all training samples and then classifies the testing sample by evaluating which class leads to the minimum representation error. This CR-based classification approach is remarkably less complex than traditional classification methods but leads to very competitive classification results. In addition, compressive sensing approach is adopted to project the high-dimensional gene expression dataset to a lower-dimensional space which nearly contains the whole information. This compression without loss is beneficial to reduce the computational load. Experiments to detect subtypes of diseases, such as leukemia and autism spectrum disorders, are performed by analyzing the gene expression. The results show that the proposed CR-based algorithm exhibits significantly higher stability and accuracy than the traditional classifiers, such as support vector machine algorithm. [ABSTRACT FROM AUTHOR]

With the recent technological developments a vast amount of high-throughput data has been profiled to understand the mechanism of complex diseases. The current bioinformatics challenge is to interpret the data and underlying biology, where efficient algorithms for analyzing heterogeneous high-throughput data using biological networks are becoming increasingly valuable. In this paper, we propose a software package based on the Prize-collecting Steiner Forest graph optimization approach. The PCSF package performs fast and user-friendly network analysis of high-throughput data by mapping the data onto a biological networks such as protein-protein interaction, gene-gene interaction or any other correlation or coexpression based networks. Using the interaction networks as a template, it determines high-confidence subnetworks relevant to the data, which potentially leads to predictions of functional units. It also interactively visualizes the resulting subnetwork with functional enrichment analysis. [ABSTRACT FROM AUTHOR]

Fuzzy co-clustering extends co-clustering by assigning membership functions to both the objects and the features, and is helpful to improve clustering accurarcy of biomedical data. In this paper, we introduce a new fuzzy co-clustering algorithm based on information bottleneck named ibFCC. The ibFCC formulates an objective function which includes a distance function that employs information bottleneck theory to measure the distance between feature data point and the feature cluster centroid. Many experiments were conducted on five biomedical datasets, and the ibFCC was compared with such prominent fuzzy (co-)clustering algorithms as FCM, FCCM, RFCC and FCCI. Experimental results showed that ibFCC could yield high quality clusters and was better than all these methods in terms of accuracy. [ABSTRACT FROM AUTHOR]

Breast cancer is an all too common disease in women, making how to effectively predict it an active research problem. A number of statistical and machine learning techniques have been employed to develop various breast cancer prediction models. Among them, support vector machines (SVM) have been shown to outperform many related techniques. To construct the SVM classifier, it is first necessary to decide the kernel function, and different kernel functions can result in different prediction performance. However, there have been very few studies focused on examining the prediction performances of SVM based on different kernel functions. Moreover, it is unknown whether SVM classifier ensembles which have been proposed to improve the performance of single classifiers can outperform single SVM classifiers in terms of breast cancer prediction. Therefore, the aim of this paper is to fully assess the prediction performance of SVM and SVM ensembles over small and large scale breast cancer datasets. The classification accuracy, ROC, F-measure, and computational times of training SVM and SVM ensembles are compared. The experimental results show that linear kernel based SVM ensembles based on the bagging method and RBF kernel based SVM ensembles with the boosting method can be the better choices for a small scale dataset, where feature selection should be performed in the data pre-processing stage. For a large scale dataset, RBF kernel based SVM ensembles based on boosting perform better than the other classifiers. [ABSTRACT FROM AUTHOR]

One of fundamental challenges in cancer studies is that varying molecular characteristics of different tumor types may lead to resistance to certain drugs. As a result, the same drug can lead to significantly different results in different types of cancer thus emphasizing the need for individualized medicine. Individual prediction of drug response has great potential to aid in improving the clinical outcome and reduce the financial costs associated with prescribing chemotherapy drugs to which the patient’s tumor might be resistant. In this paper we develop a network based classifier (NBC) method for predicting sensitivity of cell lines to anticancer drugs from transcriptome data. In the literature, this strategy has been used for predicting cancer types. Here, we extend it to estimate sensitivity of cells from different tumor types to various anticancer drugs. Furthermore, we incorporate domain specific knowledge such as the use of apoptotic gene list and clinical dose information in our method to impart biological significance to the prediction. Our experimental results suggest that our network based classifier (NBC) method outperforms existing classifiers in estimating sensitivity of cell lines for different drugs. [ABSTRACT FROM AUTHOR]

Identification of disease-causing genes is a fundamental challenge for human health studies. The phenotypic similarity among diseases may reflect the interactions at the molecular level, and phenotype comparison can be used to predict disease candidate genes. Online Mendelian Inheritance in Man (OMIM) is a database of human genetic diseases and related genes that has become an authoritative source of disease phenotypes. However, disease phenotypes have been described by free text; thus, standardization of phenotypic descriptions is needed before diseases can be compared. Several disease phenotype networks have been established in OMIM using different standardization methods. Two of these networks are important for phenotypic similarity analysis: the first and most commonly used network (mimMiner) is standardized by medical subject heading, and the other network (resnikHPO) is the first to be standardized by human phenotype ontology. This paper comprehensively evaluates for the first time the accuracy of these two networks in gene prioritization based on protein–protein interactions using large-scale, leave-one-out cross-validation experiments. The results show that both networks can effectively prioritize disease-causing genes, and the approach that relates two diseases using a logistic function improves prioritization performance. Tanimoto, one of four methods for normalizing resnikHPO, generates a symmetric network and it performs similarly to mimMiner. Furthermore, an integration of these two networks outperforms either network alone in gene prioritization, indicating that these two disease networks are complementary. [ABSTRACT FROM AUTHOR]

The identification of a subset of genes having the ability to capture the necessary information to distinguish classes of patients is crucial in bioinformatics applications. Ensemble and bagging methods have been shown to work effectively in the process of gene selection and classification. Testament to that is random forest which combines random decision trees with bagging to improve overall feature selection and classification accuracy. Surprisingly, the adoption of these methods in support vector machines has only recently received attention but mostly on classification not gene selection. This paper introduces an ensemble SVM-Recursive Feature Elimination (ESVM-RFE) for gene selection that follows the concepts of ensemble and bagging used in random forest but adopts the backward elimination strategy which is the rationale of RFE algorithm. The rationale behind this is, building ensemble SVM models using randomly drawn bootstrap samples from the training set, will produce different feature rankings which will be subsequently aggregated as one feature ranking. As a result, the decision for elimination of features is based upon the ranking of multiple SVM models instead of choosing one particular model. Moreover, this approach will address the problem of imbalanced datasets by constructing a nearly balanced bootstrap sample. Our experiments show that ESVM-RFE for gene selection substantially increased the classification performance on five microarray datasets compared to state-of-the-art methods. Experiments on the childhood leukaemia dataset show that an average 9% better accuracy is achieved by ESVM-RFE over SVM-RFE, and 5% over random forest based approach. The selected genes by the ESVM-RFE algorithm were further explored with Singular Value Decomposition (SVD) which reveals significant clusters with the selected data. [ABSTRACT FROM AUTHOR]