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The ensemble method random forests has become a popular classification tool in bioinformatics and related fields. The out-of-bag error is an error estimation technique often used to evaluate the accuracy of a random forest and to select appropriate values for tuning parameters, such as the number of candidate predictors that are randomly drawn for a split, referred to as mtry. However, for binary classification problems with metric predictors it has been shown that the out-of-bag error can overestimate the true prediction error depending on the choices of random forests parameters. Based on simulated and real data this paper aims to identify settings for which this overestimation is likely. It is, moreover, questionable whether the out-of-bag error can be used in classification tasks for selecting tuning parameters like mtry, because the overestimation is seen to depend on the parameter mtry. The simulation-based and real-data based studies with metric predictor variables performed in this paper show that the overestimation is largest in balanced settings and in settings with few observations, a large number of predictor variables, small correlations between predictors and weak effects. There was hardly any impact of the overestimation on tuning parameter selection. However, although the prediction performance of random forests was not substantially affected when using the out-of-bag error for tuning parameter selection in the present studies, one cannot be sure that this applies to all future data. For settings with metric predictor variables it is therefore strongly recommended to use stratified subsampling with sampling fractions that are proportional to the class sizes for both tuning parameter selection and error estimation in random forests. This yielded less biased estimates of the true prediction error. In unbalanced settings, in which there is a strong interest in predicting observations from the smaller classes well, sampling the same number of observations from each class is a promising alternative. [ABSTRACT FROM AUTHOR]

The process of Nuclei detection in high-grade breast cancer images is quite challenging in the case of image processing techniques due to certain heterogeneous characteristics of cancer nuclei such as enlarged and irregularly shaped nuclei, highly coarse chromatin marginalized to the nuclei periphery and visible nucleoli. Recent reviews state that existing techniques show appreciable segmentation accuracy on breast histopathology images whose nuclei are dispersed and regular in texture and shape; however, typical cancer nuclei are often clustered and have irregular texture and shape properties. This paper proposes a novel segmentation algorithm for detecting individual nuclei from Hematoxylin and Eosin (H&E) stained breast histopathology images. This detection framework estimates a nuclei saliency map using tensor voting followed by boundary extraction of the nuclei on the saliency map using a Loopy Back Propagation (LBP) algorithm on a Markov Random Field (MRF). The method was tested on both whole-slide images and frames of breast cancer histopathology images. Experimental results demonstrate high segmentation performance with efficient precision, recall and dice-coefficient rates, upon testing high-grade breast cancer images containing several thousand nuclei. In addition to the optimal performance on the highly complex images presented in this paper, this method also gave appreciable results in comparison with two recently published methods—Wienert et al. (2012) and Veta et al. (2013), which were tested using their own datasets. [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]

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]

Recent research has demonstrated that characteristic gene selection based on gene expression data remains faced with considerable challenges. This is primarily because gene expression data are typically high dimensional, negative, non-sparse and noisy. However, existing methods for data analysis are able to cope with only some of these challenges. In this paper, we address all of these challenges with a unified method: nonnegative matrix factorization via the L2,1-norm (NMF-L2,1). While L2,1-norm minimization is applied to both the error function and the regularization term, our method is robust to outliers and noise in the data and generates sparse results. The application of our method to plant and tumor gene expression data demonstrates that NMF-L2,1 can extract more characteristic genes than other existing state-of-the-art methods. [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]

Cancer classification and feature (gene) selection plays an important role in knowledge discovery in genomic data. Although logistic regression is one of the most popular classification methods, it does not induce feature selection. In this paper, we presented a new hybrid L1/2 +2 regularization (HLR) function, a linear combination of L1/2 and L2 penalties, to select the relevant gene in the logistic regression. The HLR approach inherits some fascinating characteristics from L1/2 (sparsity) and L2 (grouping effect where highly correlated variables are in or out a model together) penalties. We also proposed a novel univariate HLR thresholding approach to update the estimated coefficients and developed the coordinate descent algorithm for the HLR penalized logistic regression model. The empirical results and simulations indicate that the proposed method is highly competitive amongst several state-of-the-art methods. [ABSTRACT FROM AUTHOR]

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]

For studying cancer and genetic diseases, the issue of identifying high correlation genes from high-dimensional data is an important problem. It is a great challenge to select relevant biomarkers from gene expression data that contains some important correlation structures, and some of the genes can be divided into different groups with a common biological function, chromosomal location or regulation. In this paper, we propose a penalized accelerated failure time model CHR-DE using a non-convex regularization (local search) with differential evolution (global search) in a wrapper-embedded memetic framework. The complex harmonic regularization (CHR) can approximate to the combination and ℓq (1 ≤ q < 2) for selecting biomarkers in group. And differential evolution (DE) is utilized to globally optimize the CHR’s hyperparameters, which make CHR-DE achieve strong capability of selecting groups of genes in high-dimensional biological data. We also developed an efficient path seeking algorithm to optimize this penalized model. The proposed method is evaluated on synthetic and three gene expression datasets: breast cancer, hepatocellular carcinoma and colorectal cancer. The experimental results demonstrate that CHR-DE is a more effective tool for feature selection and learning prediction. [ABSTRACT FROM AUTHOR]

Several modern genomic technologies, such as DNA-Methylation arrays, measure spatially registered probes that number in the hundreds of thousands across multiple chromosomes. The measured probes are by themselves less interesting scientifically; instead scientists seek to discover biologically interpretable genomic regions comprised of contiguous groups of probes which may act as biomarkers of disease or serve as a dimension-reducing pre-processing step for downstream analyses. In this paper, we introduce an unsupervised feature learning technique which maps technological units (probes) to biological units (genomic regions) that are common across all subjects. We use ideas from fusion penalties and convex clustering to introduce a method for Spatial Convex Clustering, or SpaCC. Our method is specifically tailored to detecting multi-subject regions of methylation, but we also test our approach on the well-studied problem of detecting segments of copy number variation. We formulate our method as a convex optimization problem, develop a massively parallelizable algorithm to find its solution, and introduce automated approaches for handling missing values and determining tuning parameters. Through simulation studies based on real methylation and copy number variation data, we show that SpaCC exhibits significant performance gains relative to existing methods. Finally, we illustrate SpaCC’s advantages as a pre-processing technique that reduces large-scale genomics data into a smaller number of genomic regions through several cancer epigenetics case studies on subtype discovery, network estimation, and epigenetic-wide association. [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]

Integrative clustering is used to identify groups of samples by jointly analysing multiple datasets describing the same set of biological samples, such as gene expression, copy number, methylation etc. Most existing algorithms for integrative clustering assume that there is a shared consistent set of clusters across all datasets, and most of the data samples follow this structure. However in practice, the structure across heterogeneous datasets can be more varied, with clusters being joined in some datasets and separated in others. In this paper, we present a probabilistic clustering method to identify groups across datasets that do not share the same cluster structure. The proposed algorithm, Clusternomics, identifies groups of samples that share their global behaviour across heterogeneous datasets. The algorithm models clusters on the level of individual datasets, while also extracting global structure that arises from the local cluster assignments. Clusters on both the local and the global level are modelled using a hierarchical Dirichlet mixture model to identify structure on both levels. We evaluated the model both on simulated and on real-world datasets. The simulated data exemplifies datasets with varying degrees of common structure. In such a setting Clusternomics outperforms existing algorithms for integrative and consensus clustering. In a real-world application, we used the algorithm for cancer subtyping, identifying subtypes of cancer from heterogeneous datasets. We applied the algorithm to TCGA breast cancer dataset, integrating gene expression, miRNA expression, DNA methylation and proteomics. The algorithm extracted clinically meaningful clusters with significantly different survival probabilities. We also evaluated the algorithm on lung and kidney cancer TCGA datasets with high dimensionality, again showing clinically significant results and scalability of the 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]

Blood oxygenation mapping by the means of optical oximetry is of significant importance in clinical trials. This paper uses hyperspectral imaging technology to obtain in vivo images for blood oxygenation detection. The experiment involves dorsal skin fold window chamber preparation which was built on adult (8–10 weeks of age) female BALB/c nu/nu mice and in vivo image acquisition which was performed by hyperspectral imaging system. To get the accurate spatial and spectral information of targets, an automatic registration scheme is proposed. An adaptive feature detection method which combines the local threshold method and the level-set filter is presented to extract target vessels. A reliable feature matching algorithm with the correlative information inherent in hyperspectral images is used to kick out the outliers. Then, the registration images are used for blood oxygenation mapping. Registration evaluation results show that most of the false matches are removed and the smooth and concentrated spectra are obtained. This intensity invariant feature detection with outliers-removing feature matching proves to be effective in hyperspectral vessel image registration. Therefore, in vivo hyperspectral imaging system by the assistance of the proposed registration scheme provides a technique for blood oxygenation research. [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]

Gene expression data analysis has paramount implications for gene treatments, cancer diagnosis and other domains. Clustering is an important and promising tool to analyze gene expression data. Gene expression data is often characterized by a large amount of genes but with limited samples, thus various projective clustering techniques and ensemble techniques have been suggested to combat with these challenges. However, it is rather challenging to synergy these two kinds of techniques together to avoid the curse of dimensionality problem and to boost the performance of gene expression data clustering. In this paper, we employ a projective clustering ensemble (PCE) to integrate the advantages of projective clustering and ensemble clustering, and to avoid the dilemma of combining multiple projective clusterings. Our experimental results on publicly available cancer gene expression data show PCE can improve the quality of clustering gene expression data by at least 4.5% (on average) than other related techniques, including dimensionality reduction based single clustering and ensemble approaches. The empirical study demonstrates that, to further boost the performance of clustering cancer gene expression data, it is necessary and promising to synergy projective clustering with ensemble clustering. PCE can serve as an effective alternative technique for clustering gene expression data. [ABSTRACT FROM AUTHOR]

Spatial scan statistics with circular or elliptic scanning windows are commonly used for cluster detection in various applications, such as the identification of geographical disease clusters from epidemiological data. It has been pointed out that the method may have difficulty in correctly identifying non-compact, arbitrarily shaped clusters. In this paper, we evaluated the Gini coefficient for detecting irregularly shaped clusters through a simulation study. The Gini coefficient, the use of which in spatial scan statistics was recently proposed, is a criterion measure for optimizing the maximum reported cluster size. Our simulation study results showed that using the Gini coefficient works better than the original spatial scan statistic for identifying irregularly shaped clusters, by reporting an optimized and refined collection of clusters rather than a single larger cluster. We have provided a real data example that seems to support the simulation results. We think that using the Gini coefficient in spatial scan statistics can be helpful for the detection of irregularly shaped clusters. [ABSTRACT FROM AUTHOR]

Stain colour estimation is a prominent factor of the analysis pipeline in most of histology image processing algorithms. Providing a reliable and efficient stain colour deconvolution approach is fundamental for robust algorithm. In this paper, we propose a novel method for stain colour deconvolution of histology images. This approach statistically analyses the multi-resolutional representation of the image to separate the independent observations out of the correlated ones. We then estimate the stain mixing matrix using filtered uncorrelated data. We conducted an extensive set of experiments to compare the proposed method to the recent state of the art methods and demonstrate the robustness of this approach using three different datasets of scanned slides, prepared in different labs using different scanners. [ABSTRACT FROM AUTHOR]

In this paper, a total variation (TV) minimization strategy is proposed to overcome the problem of sparse spatial resolution and large amounts of noise in low dose positron emission tomography (PET) imaging reconstruction. Two types of objective function were established based on two statistical models of measured PET data, least-square (LS) TV for the Gaussian distribution and Poisson-TV for the Poisson distribution. To efficiently obtain high quality reconstructed images, the alternating direction method (ADM) is used to solve these objective functions. As compared with the iterative shrinkage/thresholding (IST) based algorithms, the proposed ADM can make full use of the TV constraint and its convergence rate is faster. The performance of the proposed approach is validated through comparisons with the expectation-maximization (EM) method using synthetic and experimental biological data. In the comparisons, the results of both LS-TV and Poisson-TV are taken into consideration to find which models are more suitable for PET imaging, in particular low-dose PET. To evaluate the results quantitatively, we computed bias, variance, and the contrast recovery coefficient (CRC) and drew profiles of the reconstructed images produced by the different methods. The results show that both Poisson-TV and LS-TV can provide a high visual quality at a low dose level. The bias and variance of the proposed LS-TV and Poisson-TV methods are 20% to 74% less at all counting levels than those of the EM method. Poisson-TV gives the best performance in terms of high-accuracy reconstruction with the lowest bias and variance as compared to the ground truth (14.3% less bias and 21.9% less variance). In contrast, LS-TV gives the best performance in terms of the high contrast of the reconstruction with the highest CRC. [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 maximal information coefficient (MIC) captures dependences between paired variables, including both functional and non-functional relationships. In this paper, we develop a new method, ChiMIC, to calculate the MIC values. The ChiMIC algorithm uses the chi-square test to terminate grid optimization and then removes the restriction of maximal grid size limitation of original ApproxMaxMI algorithm. Computational experiments show that ChiMIC algorithm can maintain same MIC values for noiseless functional relationships, but gives much smaller MIC values for independent variables. For noise functional relationship, the ChiMIC algorithm can reach the optimal partition much faster. Furthermore, the MCN values based on MIC calculated by ChiMIC can capture the complexity of functional relationships in a better way, and the statistical powers of MIC calculated by ChiMIC are higher than those calculated by ApproxMaxMI. Moreover, the computational costs of ChiMIC are much less than those of ApproxMaxMI. We apply the MIC values tofeature selection and obtain better classification accuracy using features selected by the MIC values from ChiMIC. [ABSTRACT FROM AUTHOR]

Lung 4D computed tomography (4D-CT) plays an important role in high-precision radiotherapy because it characterizes respiratory motion, which is crucial for accurate target definition. However, the manual segmentation of a lung tumor is a heavy workload for doctors because of the large number of lung 4D-CT data slices. Meanwhile, tumor segmentation is still a notoriously challenging problem in computer-aided diagnosis. In this paper, we propose a new method based on an improved graph cut algorithm with context information constraint to find a convenient and robust approach of lung 4D-CT tumor segmentation. We combine all phases of the lung 4D-CT into a global graph, and construct a global energy function accordingly. The sub-graph is first constructed for each phase. A context cost term is enforced to achieve segmentation results in every phase by adding a context constraint between neighboring phases. A global energy function is finally constructed by combining all cost terms. The optimization is achieved by solving a max-flow/min-cut problem, which leads to simultaneous and robust segmentation of the tumor in all the lung 4D-CT phases. The effectiveness of our approach is validated through experiments on 10 different lung 4D-CT cases. The comparison with the graph cut without context constraint, the level set method and the graph cut with star shape prior demonstrates that the proposed method obtains more accurate and robust segmentation results. [ABSTRACT FROM AUTHOR]

miRNAs are small non-coding RNAs that regulate gene expression by binding to the 3′-UTR of genes. Many recent studies have reported that miRNAs play important biological roles by regulating specific mRNAs or genes. Many sequence-based target prediction algorithms have been developed to predict miRNA targets. However, these methods are not designed for condition-specific target predictions and produce many false positives; thus, expression-based target prediction algorithms have been developed for condition-specific target predictions. A typical strategy to utilize expression data is to leverage the negative control roles of miRNAs on genes. To control false positives, a stringent cutoff value is typically set, but in this case, these methods tend to reject many true target relationships, i.e., false negatives. To overcome these limitations, additional information should be utilized. The literature is probably the best resource that we can utilize. Recent literature mining systems compile millions of articles with experiments designed for specific biological questions, and the systems provide a function to search for specific information. To utilize the literature information, we used a literature mining system, BEST, that automatically extracts information from the literature in PubMed and that allows the user to perform searches of the literature with any English words. By integrating omics data analysis methods and BEST, we developed Context-MMIA, a miRNA-mRNA target prediction method that combines expression data analysis results and the literature information extracted based on the user-specified context. In the pathway enrichment analysis using genes included in the top 200 miRNA-targets, Context-MMIA outperformed the four existing target prediction methods that we tested. In another test on whether prediction methods can re-produce experimentally validated target relationships, Context-MMIA outperformed the four existing target prediction methods. In summary, Context-MMIA allows the user to specify a context of the experimental data to predict miRNA targets, and we believe that Context-MMIA is very useful for predicting condition-specific miRNA targets. [ABSTRACT FROM AUTHOR]

We apply the Google matrix algorithms for analysis of interactions and influence of 37 cancer types, 203 cancer drugs and 195 world countries using the network of 5 416 537 English Wikipedia articles with all their directed hyperlinks. The PageRank algorithm provides a ranking of cancers which has 60% and 70% overlaps with the top 10 deadliest cancers extracted from World Health Organization GLOBOCAN 2018 and Global Burden of Diseases Study 2017, respectively. The recently developed reduced Google matrix algorithm gives networks of interactions between cancers, drugs and countries taking into account all direct and indirect links between these selected 435 entities. These reduced networks allow to obtain sensitivity of countries to specific cancers and drugs. The strongest links between cancers and drugs are in good agreement with the approved medical prescriptions of specific drugs to specific cancers. We argue that this analysis of knowledge accumulated in Wikipedia provides useful complementary global information about interdependencies between cancers, drugs and world countries. [ABSTRACT FROM AUTHOR]

In transcriptomics, micro RNAs (miRNAs) has gained much interest especially as potential disease indicators. However, apart from holding a great promise related to their clinical application, a lot of inconsistent results have been published. Our aim was to compare the miRNA expression levels in ovarian cancer and healthy subjects using the Bayesian multilevel model and to assess their potential usefulness in diagnosis. We have analyzed a case-control observational data on expression profiling of 49 preselected miRNA-based ovarian cancer indicators in 119 controls and 59 patients. A Bayesian multilevel model was used to characterize the effect of disease on miRNA levels controlling for differences in age and body weight. The difference between the miRNA level and health status of the patient on the scale of the data variability were discussed in the context of their potential usefulness in diagnosis. Additionally, the cross-validated area under the ROC curve (AUC) was used to assess the expected out-of-sample discrimination index of a different sets of miRNAs. The proposed model allowed us to describe the set of miRNA levels in patients and controls. Three highly correlated miRNAs: miR-101-3p, miR-142-5p, miR-148a-3p rank the highest with almost identical effect sizes that ranges from 0.45 to 1.0. For those miRNAs the credible interval for AUC ranged from 0.63 to 0.67 indicating their limited discrimination potential. A little benefit in adding information from other miRNAs was observed. There were several miRNAs in the dataset (miR-604, hsa-miR-221-5p) for which inferences were uncertain. For those miRNAs more experimental effort is needed to fully assess their effect in the context of new hits discovery and usefulness as disease indicators. The proposed multilevel Bayesian model can be used to characterize the panel of miRNA profile and to assess the difference in expression levels between healthy and cancer individuals. [ABSTRACT FROM AUTHOR]

Spatial scan statistics are widely used for cluster detection analysis in geographical disease surveillance. While this method has been developed for various types of data such as binary, count, and continuous data, spatial scan statistics for matched case-control data, which often arise in spatial epidemiology, have not been considered. We propose spatial scan statistics for matched case-control data. The proposed test statistics consider the correlations between matched pairs. We evaluate the statistical power and cluster detection accuracy of the proposed methods through simulations compared to the Bernoulli-based method. We illustrate the proposed methods using a real data example. The simulation study clearly revealed that the proposed methods had higher power and higher accuracy for detecting spatial clusters for matched case-control data than the Bernoulli-based spatial scan statistic. The cluster detection result of the real data example also appeared to reflect a higher power of the proposed methods. The proposed methods are very useful for spatial cluster detection for matched case-control data. [ABSTRACT FROM AUTHOR]

Acute Promyelocytic Leukemia (APL) is a rare and potentially lethal condition in which risk-based therapy often leads to better outcomes. Because of its rarity and relatively high overall survival rate, prospective randomized trials to investigate alternative APL treatment schedules are challenging. Mathematical models may provide useful information in this regard. We collected clinical data from 38 patients treated for APL under the International Consortium on Acute Leukemia (ICAL) protocol and laboratory data during induction therapy. We propose a mathematical model that represents the dynamics of leukocytes in peripheral blood and the effect of ICAL treatment on the disease’s dynamics. We observe that our cohort presents demographic characteristics and clinical outcomes similar to previous clinical trials on APL. Over a follow-up period of 41.8 months, the relapse-free survival and overall survival at two years are both found to be 78.7%. For two selected patients, the model produces a good fit to the clinical data. Information such as the response to treatment and risk of relapse can be derived from the model, and this may assist in clinical practice and the design of clinical trials. [ABSTRACT FROM AUTHOR]

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the lower limit of detection (i.e., a measurable lesion) and confounding variables, such as tumor microenvironment, and immune responses may cause and mask deviations from exponential growth models. In this work, we present alternative growth models to investigate the presence of an Allee effect in cancer cells seeded at low cell densities in a controlled in vitro setting. We propose a stochastic modeling framework to disentangle expected deviations due to small population size stochastic effects from cooperative growth and use the moment approach for stochastic parameter estimation to calibrate the observed growth trajectories. We validate the framework on simulated data and apply this approach to longitudinal cell proliferation data of BT-474 luminal B breast cancer cells. We find that cell population growth kinetics are best described by a model structure that considers the Allee effect, in that the birth rate of tumor cells increases with cell number in the regime of small population size. This indicates a potentially critical role of cooperative behavior among tumor cells at low cell densities with relevance to early stage growth patterns of emerging and relapsed tumors. [ABSTRACT FROM AUTHOR]

Quantification of the effect of spatial tumour sampling on the patterns of mutations detected in next-generation sequencing data is largely lacking. Here we use a spatial stochastic cellular automaton model of tumour growth that accounts for somatic mutations, selection, drift and spatial constraints, to simulate multi-region sequencing data derived from spatial sampling of a neoplasm. We show that the spatial structure of a solid cancer has a major impact on the detection of clonal selection and genetic drift from both bulk and single-cell sequencing data. Our results indicate that spatial constrains can introduce significant sampling biases when performing multi-region bulk sampling and that such bias becomes a major confounding factor for the measurement of the evolutionary dynamics of human tumours. We also propose a statistical inference framework that incorporates spatial effects within a growing tumour and so represents a further step forwards in the inference evolutionary dynamics from genomic data. Our analysis shows that measuring cancer evolution using next-generation sequencing while accounting for the numerous confounding factors remains challenging. However, mechanistic model-based approaches have the potential to capture the sources of noise and better interpret the data. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian tumors are the most common diagnostic challenge for gynecologists and ultrasound examination has become the main technique for assessment of ovarian pathology and for preoperative distinction between malignant and benign ovarian tumors. However, ultrasonography is highly examiner-dependent and there may be an important variability between two different specialists when examining the same case. The objective of this work is the evaluation of different well-known Machine Learning (ML) systems to perform the automatic categorization of ovarian tumors from ultrasound images. Methods: We have used a real patient database whose input features have been extracted from 348 images, from the IOTA tumor images database, holding together with the class labels of the images. For each patient case and ultrasound image, its input features have been previously extracted using Fourier descriptors computed on the Region Of Interest (ROI). Then, four ML techniques are considered for performing the classification stage: K-Nearest Neighbors (KNN), Linear Discriminant (LD), Support Vector Machine (SVM) and Extreme Learning Machine (ELM). Results: According to our obtained results, the KNN classifier provides inaccurate predictions (less than 60% of accuracy) independently of the size of the local approximation, whereas the classifiers based on LD, SVM and ELM are robust in this biomedical classification (more than 85% of accuracy). Conclusions: ML methods can be efficiently used for developing the classification stage in computer-aided diagnosis systems of ovarian tumor from ultrasound images. These approaches are able to provide automatic classification with a high rate of accuracy. Future work should aim at enhancing the classifier design using ensemble techniques. Another ongoing work is to exploit different kind of features extracted from ultrasound images. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors. Methods: A patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients’ baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted. Results: Drug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX. Conclusions: TNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option. [ABSTRACT FROM AUTHOR]

We investigate the personalisation and prediction accuracy of mathematical models for white blood cell (WBC) count dynamics during consolidation treatment using intermediate or high-dose cytarabine (Ara-C) in acute myeloid leukaemia (AML). Ara-C is the clinically most relevant cytotoxic agent for AML treatment. We extend a mathematical model of myelosuppression and a pharmacokinetic model of Ara-C with different hypotheses of Ara-C’s pharmacodynamic effects. We cross-validate the 12 model variations using dense WBC count measurements from 23 AML patients. Surprisingly, the prediction accuracy remains satisfactory in each of the models despite different modelling hypotheses. Therefore, we compare average clinical and calculated WBC recovery times for different Ara-C schedules as a successful methodology for model discrimination. As a result, a new hypothesis of a secondary pharmacodynamic effect on the proliferation rate seems plausible. Furthermore, we demonstrate the impact of treatment timing on subsequent nadir values based on personalised predictions as a possibility for influencing/controlling myelosuppression. [ABSTRACT FROM AUTHOR]

Background: Gene shaving (GS) is an essential and challenging tools for biomedical researchers due to the large number of genes in human genome and the complex nature of biological networks. Most GS methods are not applicable to non-linear and multi-view data sets. While the kernel based methods can overcome these problems, a well-founded positive definite kernel based GS method has yet to be proposed for biomedical data analysis. Methods and findings: Since the kernel based methods on genomic information can improve the prediction of diseases, here we proposed a noble method, “kernel based gene shaving” which is based on the influence function of kernel canonical correlation analysis. To investigate the performance of the proposed method in comparison to state-of-the-art-method in gene saving, we analyzed extensive simulated and real microarray gene expression data set. The performance metrics including true positive rate, true negative rate, false positive rate, false negative rate, misclassification error rate, the false discovery rate and area under curves were computed for each methods. In colon cancer data analysis, the proposed method identified a significant subsets of 210 genes out of 2000 genes and suggestive superior performance compared with other methods. The proposed method can be applied to the study of other disease process where two view data is a common task. Conclusions: We addressed the challenge of finding unique kernel based GS methods by using the influence function of kernel canonical correlation analysis. The proposed method has shown to have better performance than state-of-the-art-methods in gene saving and has identified many more significant gene interactions, suggesting that genes function in a concerted effort in colon cancer. In similar biomedical data analysis, kernel based methods could be applied to select a potential subset of genes. The positive definite kernel based methods can overcome the non-linearity problem and improve the prediction process. [ABSTRACT FROM AUTHOR]

Estimating and selecting risk factors with extremely low prevalences of exposure for a binary outcome is a challenge because classical standard techniques, markedly logistic regression, often fail to provide meaningful results in such settings. While penalized regression methods are widely used in high-dimensional settings, we were able to show their usefulness in low-dimensional settings as well. Specifically, we demonstrate that Firth correction, ridge, the lasso and boosting all improve the estimation for low-prevalence risk factors. While the methods themselves are well-established, comparison studies are needed to assess their potential benefits in this context. This is done here using the dataset of a large unmatched case-control study from France (2005-2008) about the relationship between prescription medicines and road traffic accidents and an accompanying simulation study. Results show that the estimation of risk factors with prevalences below 0.1% can be drastically improved by using Firth correction and boosting in particular, especially for ultra-low prevalences. When a moderate number of low prevalence exposures is available, we recommend the use of penalized techniques. [ABSTRACT FROM AUTHOR]

The inherent capacity of somatic cells to switch their phenotypic status in response to damage stimuli in vivo might have a pivotal role in ageing and cancer. However, how the entry-exit mechanisms of phenotype reprogramming are established remains poorly understood. In an attempt to elucidate such mechanisms, we herein introduce a stochastic model of combined epigenetic regulation (ER)-gene regulatory network (GRN) to study the plastic phenotypic behaviours driven by ER heterogeneity. To deal with such complex system, we additionally formulate a multiscale asymptotic method for stochastic model reduction, from which we derive an efficient hybrid simulation scheme. Our analysis of the coupled system reveals a regime of tristability in which pluripotent stem-like and differentiated steady-states coexist with a third indecisive state, with ER driving transitions between these states. Crucially, ER heterogeneity of differentiation genes is for the most part responsible for conferring abnormal robustness to pluripotent stem-like states. We formulate epigenetic heterogeneity-based strategies capable of unlocking and facilitating the transit from differentiation-refractory (stem-like) to differentiation-primed epistates. The application of the hybrid numerical method validates the likelihood of such switching involving solely kinetic changes in epigenetic factors. Our results suggest that epigenetic heterogeneity regulates the mechanisms and kinetics of phenotypic robustness of cell fate reprogramming. The occurrence of tunable switches capable of modifying the nature of cell fate reprogramming might pave the way for new therapeutic strategies to regulate reparative reprogramming in ageing and cancer. [ABSTRACT FROM AUTHOR]

MiRNAs and proteins play important roles in different stages of breast tumor development and serve as biomarkers for the early diagnosis of breast cancer. A new algorithm that combines machine learning algorithms and multilayer complex network analysis is hereby proposed to explore the potential diagnostic values of miRNAs and proteins. XGBoost and random forest algorithms were employed to screen the most important miRNAs and proteins. Maximal information coefficient was applied to assess intralayer and interlayer connection. A multilayer complex network was constructed to identify miRNAs and proteins that could serve as biomarkers for breast cancer. Proteins and miRNAs that are nodes in the network were subsequently categorized into two network layers considering their distinct functions. The betweenness centrality was used as the first measurement of the importance of the nodes within each single layer. The degree of the nodes was chosen as the second measurement to map their signalling pathways. By combining these two measurements into one score and comparing the difference of the same candidate between normal tissue and cancer tissue, this novel multilayer network analysis could be applied to successfully identify molecules associated with breast cancer. [ABSTRACT FROM AUTHOR]

Increasing evidence has indicated that microRNAs(miRNAs) play vital roles in various pathological processes and thus are closely related with many complex human diseases. The identification of potential disease-related miRNAs offers new opportunities to understand disease etiology and pathogenesis. Although there have been numerous computational methods proposed to predict reliable miRNA-disease associations, they suffer from various limitations that affect the prediction accuracy and their applicability. In this study, we develop a novel method to discover disease-related candidate miRNAs based on Adaptive Multi-View Multi-Label learning(AMVML). Specifically, considering the inherent noise existed in the current dataset, we propose to learn a new affinity graph adaptively for both diseases and miRNAs from multiple similarity profiles. We then simultaneously update the miRNA-disease association predicted from both spaces based on multi-label learning. In particular, we prove the convergence of AMVML theoretically and the corresponding analysis indicates that it has a fast convergence rate. To comprehensively illustrate the prediction performance of our method, we compared AMVML with four state-of-the-art methods under different validation frameworks. As a result, our method achieves comparable performance under various evaluation metrics, which suggests that our method is capable of discovering greater number of true miRNA-disease associations. The case study conducted on thyroid neoplasms further identified a potential diagnostic biomarker. Together, the experimental results confirms the utility of our method and we anticipate that our method could serve as a reliable and efficient tool for uncovering novel disease-related miRNAs. [ABSTRACT FROM AUTHOR]

Since their inception, several tools have been developed for cluster analysis and heatmap construction. The application of such tools to the number and types of genome-wide data available from next generation sequencing (NGS) technologies requires the adaptation of statistical concepts, such as in defining a most variable gene set, and more intricate cluster analyses method to address multiple omic data types. Additionally, the growing number of publicly available datasets has created the desire to estimate the statistical significance of a gene signature derived from one dataset to similarly group samples based on another dataset. The currently available number of tools and their combined use for generating heatmaps, along with the several adaptations of statistical concepts for addressing the higher dimensionality of genome-wide NGS-derived data, has created a further challenge in the ability to replicate heatmap results. We introduce NOJAH (NOt Just Another Heatmap), an interactive tool that defines and implements a workflow for genome-wide cluster analysis and heatmap construction by creating and combining several tools into a single user interface. NOJAH includes several newly developed scripts for techniques that though frequently applied are not sufficiently documented to allow for replicability of results. These techniques include: defining a most variable gene set (a.k.a., ‘core genes’), estimating the statistical significance of a gene signature to separate samples into clusters, and performing a result merging integrated cluster analysis. With only a user uploaded dataset, NOJAH provides as output, among other things, the minimum documentation required for replicating heatmap results. Additionally, NOJAH contains five different existing R packages that are connected in the interface by their functionality as part of a defined workflow for genome-wide cluster analysis. The NOJAH application tool is available at with corresponding source code available at . [ABSTRACT FROM AUTHOR]

In more recent years, a significant increase in the number of available biological experiments has taken place due to the widespread use of massive sequencing data. Furthermore, the continuous developments in the machine learning and in the high performance computing areas, are allowing a faster and more efficient analysis and processing of this type of data. However, biological information about a certain disease is normally widespread due to the use of different sequencing technologies and different manufacturers, in different experiments along the years around the world. Thus, nowadays it is of paramount importance to attain a correct integration of biologically-related data in order to achieve genuine benefits from them. For this purpose, this work presents an integration of multiple Microarray and RNA-seq platforms, which has led to the design of a multiclass study by collecting samples from the main four types of leukemia, quantified at gene expression. Subsequently, in order to find a set of differentially expressed genes with the highest discernment capability among different types of leukemia, an innovative parameter referred to as coverage is presented here. This parameter allows assessing the number of different pathologies that a certain gen is able to discern. It has been evaluated together with other widely known parameters under assessment of an ANOVA statistical test which corroborated its filtering power when the identified genes are subjected to a machine learning process at multiclass level. The optimal tuning of gene extraction evaluated parameters by means of this statistical test led to the selection of 42 highly relevant expressed genes. By the use of minimum-Redundancy Maximum-Relevance (mRMR) feature selection algorithm, these genes were reordered and assessed under the operation of four different classification techniques. Outstanding results were achieved by taking exclusively the first ten genes of the ranking into consideration. Finally, specific literature was consulted on this last subset of genes, revealing the occurrence of practically all of them with biological processes related to leukemia. At sight of these results, this study underlines the relevance of considering a new parameter which facilitates the identification of highly valid expressed genes for simultaneously discerning multiple types of leukemia. [ABSTRACT FROM AUTHOR]

Tumors are heterogeneous in the sense that they consist of multiple subpopulations of cells, referred to as subclones, each of which is characterized by a distinct profile of genomic variations such as somatic mutations. Inferring the underlying clonal landscape has become an important topic in that it can help in understanding cancer development and progression, and thereby help in improving treatment. We describe a novel state-space model, based on the feature allocation framework and an efficient sequential Monte Carlo (SMC) algorithm, using the somatic mutation data obtained from tumor samples to estimate the number of subclones, as well as their characterization. Our approach, by design, is capable of handling any number of mutations. Via extensive simulations, our method exhibits high accuracy, in most cases, and compares favorably with existing methods. Moreover, we demonstrated the validity of our method through analyzing real tumor samples from patients from multiple cancer types (breast, prostate, and lung). Our results reveal driver mutation events specific to cancer types, and indicate clonal expansion by manual phylogenetic analysis. MATLAB code and datasets are available to download at: . [ABSTRACT FROM AUTHOR]

The current research study is concerned with the automated differentiation between histopathological slides from colon tissues with respect to four classes (healthy tissue and cancerous of grades 1, 2 or 3) through an optimized ensemble of predictors. Six distinct classifiers with prediction accuracies ranging from 87% to 95% are considered for the task. The proposed method of combining them takes into account the probabilities of the individual classifiers for each sample to be assigned to any of the four classes, optimizes weights for each technique by differential evolution and attains an accuracy that is significantly better than the individual results. Moreover, a degree of confidence is defined that would allow the pathologists to separate the data into two distinct sets, one that is correctly classified with a high level of confidence and the rest that would need their further attention. The tandem is also validated on other benchmark data sets. The proposed methodology proves to be efficient in improving the classification accuracy of each algorithm taken separately and performs reasonably well on other data sets, even with default weights. In addition, by establishing a degree of confidence the method becomes more viable for use by actual practitioners. [ABSTRACT FROM AUTHOR]

Different performance measures are used to assess the behaviour, and to carry out the comparison, of classifiers in Machine Learning. Many measures have been defined on the literature, and among them, a measure inspired by Shannon’s entropy named the Confusion Entropy (CEN). In this work we introduce a new measure, MCEN, by modifying CEN to avoid its unwanted behaviour in the binary case, that disables it as a suitable performance measure in classification. We compare MCEN with CEN and other performance measures, presenting analytical results in some particularly interesting cases, as well as some heuristic computational experimentation. [ABSTRACT FROM AUTHOR]

Introduction: Surveys indicate that patients, particularly those suffering from chronic conditions, strongly benefit from the information found in social networks and online forums. One challenge in accessing online health information is to differentiate between factual and more subjective information. In this work, we evaluate the feasibility of exploiting lexical, syntactic, semantic, network-based and emotional properties of texts to automatically classify patient-generated contents into three types: “experiences”, “facts” and “opinions”, using machine learning algorithms. In this context, our goal is to develop automatic methods that will make online health information more easily accessible and useful for patients, professionals and researchers. Material and methods: We work with a set of 3000 posts to online health forums in breast cancer, morbus crohn and different allergies. Each sentence in a post is manually labeled as “experience”, “fact” or “opinion”. Using this data, we train a support vector machine algorithm to perform classification. The results are evaluated in a 10-fold cross validation procedure. Results: Overall, we find that it is possible to predict the type of information contained in a forum post with a very high accuracy (over 80 percent) using simple text representations such as word embeddings and bags of words. We also analyze more complex features such as those based on the network properties, the polarity of words and the verbal tense of the sentences and show that, when combined with the previous ones, they can boost the results. [ABSTRACT FROM AUTHOR]

Chromosomal aberrations, such as micronuclei (MN), have served as biomarkers of genotoxic exposure and cancer risk. Guidelines for the process of scoring MN have been presented by the HUman MicroNucleus (HUMN) project. However, these guidelines were developed for assay performance but do not address how to statistically analyze the data generated by the assay. This has led to the application of various statistical methods that may render different interpretations and conclusions. By combining MN with data from other high-throughput genomic technologies such as gene expression microarray data, we may elucidate molecular features involved in micronucleation. Traditional methods that can model discrete (synonymously, count) data, such as MN frequency, require that the number of explanatory variables (P) is less than the number of samples (N). Due to this limitation, penalized models have been developed to enable model fitting for such over-parameterized datasets. Because penalized models in the discrete response setting are lacking, particularly when the count outcome is over-dispersed, herein we present our penalized negative binomial regression model that can be fit when P > N. Using simulation studies we demonstrate the performance of our method in comparison to commonly used penalized Poisson models when the outcome is over-dispersed and applied it to MN frequency and gene expression data collected as part of the Norwegian Mother and Child Cohort Study. Our R package is available for download from the Comprehensive R Archive Network and can be applied to datasets having a discrete outcome that is either Poisson or negative binomial distributed and a high-dimensional covariate space. [ABSTRACT FROM AUTHOR]

Purpose: In dynamic contrast enhanced (DCE) MRI, separation of signal contributions from perfusion and leakage requires robust estimation of parameters in a pharmacokinetic model. We present and quantify the performance of a method to compute tissue hemodynamic parameters from DCE data using established pharmacokinetic models. Methods: We propose a Bayesian scheme to obtain perfusion metrics from DCE MRI data. Initial performance is assessed through digital phantoms of the extended Tofts model (ETM) and the two-compartment exchange model (2CXM), comparing the Bayesian scheme to the standard Levenberg-Marquardt (LM) algorithm. Digital phantoms are also invoked to identify limitations in the pharmacokinetic models related to measurement conditions. Using computed maps of the extra vascular volume (ve) from 19 glioma patients, we analyze differences in the number of un-physiological high-intensity ve values for both ETM and 2CXM, using a one-tailed paired t-test assuming un-equal variance. Results: The Bayesian parameter estimation scheme demonstrated superior performance over the LM technique in the digital phantom simulations. In addition, we identified limitations in parameter reliability in relation to scan duration for the 2CXM. DCE data for glioma and cervical cancer patients was analyzed with both algorithms and demonstrated improvement in image readability for the Bayesian method. The Bayesian method demonstrated significantly fewer non-physiological high-intensity ve values for the ETM (p<0.0001) and the 2CXM (p<0.0001). Conclusion: We have demonstrated substantial improvement of the perceptive quality of pharmacokinetic parameters from advanced compartment models using the Bayesian parameter estimation scheme as compared to the LM technique. [ABSTRACT FROM AUTHOR]