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Primary data collected during a research study is often shared and may be reused for new studies. To assess the extent of data sharing in favourable circumstances and whether data sharing checks can be automated, this article investigates summary statistics from primary human genome-wide association studies (GWAS). This type of data is highly suitable for sharing because it is a standard research output, is straightforward to use in future studies (e.g., for secondary analysis), and may be already stored in a standard format for internal sharing within multi-site research projects. Manual checks of 1799 articles from 2010 and 2017 matching a simple PubMed query for molecular epidemiology GWAS were used to identify 314 primary human GWAS papers. Of these, only 13% reported the location of a complete set of GWAS summary data, increasing from 3% in 2010 to 23% in 2017. Whilst information about whether data was shared was typically located clearly within a data availability statement, the exact nature of the shared data was usually unspecified. Thus, data sharing is the exception even in suitable research fields with relatively strong data sharing norms. Moreover, the lack of clear data descriptions within data sharing statements greatly complicates the task of automatically characterising shared data sets. [ABSTRACT FROM AUTHOR]

In this paper, a new modification of the Lomax distribution is considered named as Lomax exponential distribution (LE). The proposed distribution is quite flexible in modeling the lifetime data with both decreasing and increasing shapes (non-monotonic). We derive the explicit expressions for the incomplete moments, quantile function, the density function for the order statistics etc. The Renyi entropy for the proposed distribution is also obtained. Moreover, the paper discusses the estimates of the parameters by the usual maximum likelihood estimation method along with determining the information matrix. In addition, the potentiality of the proposed distribution is illustrated using two real data sets. To judge the performance of the model, the goodness of fit measures, AIC, CAIC, BIC, and HQIC are used. Form the results it is concluded that the proposed model performs better than the Lomax distribution, Weibull Lomax distribution, and exponential Lomax distribution. [ABSTRACT FROM AUTHOR]

In a recidivism prediction context, there is no consensus on which modeling strategy should be followed for obtaining an optimal prediction model. In previous papers, a range of statistical and machine learning techniques were benchmarked on recidivism data with a binary outcome. However, two important tree ensemble methods, namely gradient boosting and random forests were not extensively evaluated. In this paper, we further explore the modeling potential of these techniques in the binary outcome criminal prediction context. Additionally, we explore the predictive potential of classical statistical and machine learning methods for censored time-to-event data. A range of statistical manually specified statistical and (semi-)automatic machine learning models is fitted on Dutch recidivism data, both for the binary outcome case and censored outcome case. To enhance generalizability of results, the same models are applied to two historical American data sets, the North Carolina prison data. For all datasets, (semi-) automatic modeling in the binary case seems to provide no improvement over an appropriately manually specified traditional statistical model. There is however evidence of slightly improved performance of gradient boosting in survival data. Results on the reconviction data from two sources suggest that both statistical and machine learning should be tried out for obtaining an optimal model. Even if a flexible black-box model does not improve upon the predictions of a manually specified model, it can serve as a test whether important interactions are missing or other misspecification of the model are present and can thus provide more security in the modeling process. [ABSTRACT FROM AUTHOR]

Reversible Data Hiding (RDH) techniques have gained popularity over the last two decades, where data is embedded in an image in such a way that the original image can be restored. Earlier works on RDH was based on the Image Histogram Modification that uses the peak point to embed data in the image. More recent works focus on the Difference Image Histogram Modification that exploits the fact that the neighbouring pixels of an image are highly correlated and therefore the difference of image makes more space to embed large amount of data. In this paper we propose a framework to increase the embedding capacity of reversible data hiding techniques that use a difference of image to embed data. The main idea is that, instead of taking the difference of the neighboring pixels, we rearrange the columns (or rows) of the image in a way that enhances the smooth regions of an image. Any difference based technique to embed data can then be used in the transformed image. The proposed method is applied on different types of images including textures, patterns and publicly available images. Experimental results demonstrate that the proposed method not only increases the message embedding capacity of a given image by more than 50% but also the visual quality of the marked image containing the message is more than the visual quality obtained by existing state-of-the-art reversible data hiding technique. The proposed technique is also verified by Pixel Difference Histogram (PDH) Stegoanalysis and results demonstrate that marked images generated by proposed method is undetectable by PDH analysis. [ABSTRACT FROM AUTHOR]

Typically discretisation procedures are implemented as a part of initial pre-processing of data, before knowledge mining is employed. It means that conclusions and observations are based on reduced data, as usually by discretisation some information is discarded. The paper presents a different approach, with taking advantage of discretisation executed after data mining. In the described study firstly decision rules were induced from real-valued features. Secondly, data sets were discretised. Using categories found for attributes, in the third step conditions included in inferred rules were translated into discrete domain. The properties and performance of rule classifiers were tested in the domain of stylometric analysis of texts, where writing styles were defined through quantitative attributes of continuous nature. The performed experiments show that the proposed processing leads to sets of rules with significantly reduced sizes while maintaining quality of predictions, and allows to test many data discretisation methods at the acceptable computational costs. [ABSTRACT FROM AUTHOR]

Faced with limitations in data availability, funding, and time constraints, ecologists are often tasked with making predictions beyond the range of their data. In ecological studies, it is not always obvious when and where extrapolation occurs because of the multivariate nature of the data. Previous work on identifying extrapolation has focused on univariate response data, but these methods are not directly applicable to multivariate response data, which are common in ecological investigations. In this paper, we extend previous work that identified extrapolation by applying the predictive variance from the univariate setting to the multivariate case. We propose using the trace or determinant of the predictive variance matrix to obtain a scalar value measure that, when paired with a selected cutoff value, allows for delineation between prediction and extrapolation. We illustrate our approach through an analysis of jointly modeled lake nutrients and indicators of algal biomass and water clarity in over 7000 inland lakes from across the Northeast and Mid-west US. In addition, we outline novel exploratory approaches for identifying regions of covariate space where extrapolation is more likely to occur using classification and regression trees. The use of our Multivariate Predictive Variance (MVPV) measures and multiple cutoff values when exploring the validity of predictions made from multivariate statistical models can help guide ecological inferences. [ABSTRACT FROM AUTHOR]

Knowledge bases are largely developed and utilized in academic and industrial fields, such as DBPedia, VIAF, LoC, Getty, and which are published in the Linked Data format. However, if you want to view different resources on these knowledge bases, you have to switch between different web pages from these resources. Therefore, we proposed a decentralized data hub named SinoPedia, which consists of several linked data services and can re-publish these RDF data in one platform. Firstly, these different Linked Data services include: Linked Data Transformation Service (LDTS), Linked Data Query Service (LDQS), Linked Data Publishing Service (LDPS) and Linked Data Knowledge Service (LDKS). The resource URI is the basis and core of the linked data, thus we will focus on the resource forwarding mechanism in LDPS service which can rewrite resource URI using a global and standard format among knowledge bases. Some knowledge bases were configured in SinoPedia platform in this paper. In addition to the above services, Linked Data Reasoning Service (LDRS) and Linked Data Intelligence Service (LDIS) will be added to the platform in the future. In short, all of these Linked Data Services will form the core framework in order to providing a good linked data application ecosystem. [ABSTRACT FROM AUTHOR]

The clustering of time series has attracted growing research interest in recent years. The most popular clustering methods assume that the time series are only linearly dependent but this assumption usually fails in practice. To overcome this limitation, in this paper, we study clustering methods applicable to time series with a general and dependent structure. We propose a copula-based distance to measure dissimilarity among time series and consider an estimator for it, where the strong consistency of the estimator is guaranteed. Once the pairwise distance matrix for time series has been obtained, we apply a hierarchical clustering algorithm to cluster the time series and ensure its consistency. Numerical studies, including a large number of simulations and analysis of practical data, show that our method performs well. [ABSTRACT FROM AUTHOR]

This paper introduces a new method for acquiring and interpreting data on cognitive (or perceptual) networks. The proposed method involves the collection of multiple reports on randomly chosen pairs of individuals, and statistical means for aggregating these reports into data of conventional sociometric form. We refer to the method as “perceptual tomography” to emphasize that it aggregates multiple 3rd-party data on the perceived presence or absence of individual properties and pairwise relationships. Key features of the method include its low respondent burden, flexible interpretation, as well as its ability to find “robust intransitive” ties in the form of perceived non-edges. This latter feature, in turn, allows for the application of conventional balance clustering routines to perceptual tomography data. In what follows, we will describe both the method and an example of the implementation of the method from a recent community study among Alaska Natives. Interview data from 170 community residents is used to ascribe 4446 perceived relationships (2146 perceived edges, 2300 perceived non-edges) among 393 community members, and to assert the perceived presence (or absence) of 16 community-oriented helping behaviors to each individual in the community. Using balance theory-based partitioning of the perceptual network, we show that people in the community perceive distinct helping roles as structural associations among community members. The fact that role classes can be detected in network renderings of “tomographic” perceptual information lends support to the suggestion that this method is capable of producing meaningful new kinds of data about perceptual networks. [ABSTRACT FROM AUTHOR]

In spacecraft electrical signal characteristic data, there exists a large amount of data with high-dimensional features, a high computational complexity degree, and a low rate of identification problems, which causes great difficulty in fault diagnosis of spacecraft electronic load systems. This paper proposes a feature extraction method that is based on deep belief networks (DBN) and a classification method that is based on the random forest (RF) algorithm; The proposed algorithm mainly employs a multi-layer neural network to reduce the dimension of the original data, and then, classification is applied. Firstly, we use the method of wavelet denoising, which was used to pre-process the data. Secondly, the deep belief network is used to reduce the feature dimension and improve the rate of classification for the electrical characteristics data. Finally, we used the random forest algorithm to classify the data and comparing it with other algorithms. The experimental results show that compared with other algorithms, the proposed method shows excellent performance in terms of accuracy, computational efficiency, and stability in addressing spacecraft electrical signal data. [ABSTRACT FROM AUTHOR]

We show that occupancy models are more difficult to fit than is generally appreciated because the estimating equations often have multiple solutions, including boundary estimates which produce fitted probabilities of zero or one. The estimates are unstable when the data are sparse, making them difficult to interpret, and, even in ideal situations, highly variable. As a consequence, making accurate inference is difficult. When abundance varies over sites (which is the general rule in ecology because we expect spatial variance in abundance) and detection depends on abundance, the standard analysis suffers bias (attenuation in detection, biased estimates of occupancy and potentially finding misleading relationships between occupancy and other covariates), asymmetric sampling distributions, and slow convergence of the sampling distributions to normality. The key result of this paper is that the biases are of similar magnitude to those obtained when we ignore nondetection entirely. The fact that abundance is subject to detection error and hence is not directly observable, means that we cannot tell when bias is present (or, equivalently, how large it is) and we cannot adjust for it. This implies that we cannot tell which fit is better: the fit from the occupancy model or the fit ignoring the possibility of detection error. Therefore trying to adjust occupancy models for non-detection can be as misleading as ignoring non-detection completely. Ignoring nondetection can actually be better than trying to adjust for it. [ABSTRACT FROM AUTHOR]

Traditional k-means and most k-means variants are still computationally expensive for large datasets, such as microarray data, which have large datasets with large dimension size d. In k-means clustering, we are given a set of n data points in d-dimensional space Rd and an integer k. The problem is to determine a set of k points in Rd, called centers, so as to minimize the mean squared distance from each data point to its nearest center. In this work, we develop a novel k-means algorithm, which is simple but more efficient than the traditional k-means and the recent enhanced k-means. Our new algorithm is based on the recently established relationship between principal component analysis and the k-means clustering. We provided the correctness proof for this algorithm. Results obtained from testing the algorithm on three biological data and six non-biological data (three of these data are real, while the other three are simulated) also indicate that our algorithm is empirically faster than other known k-means algorithms. We assessed the quality of our algorithm clusters against the clusters of a known structure using the Hubert-Arabie Adjusted Rand index (ARIHA). We found that when k is close to d, the quality is good (ARIHA>0.8) and when k is not close to d, the quality of our new k-means algorithm is excellent (ARIHA>0.9). In this paper, emphases are on the reduction of the time requirement of the k-means algorithm and its application to microarray data due to the desire to create a tool for clustering and malaria research. However, the new clustering algorithm can be used for other clustering needs as long as an appropriate measure of distance between the centroids and the members is used. This has been demonstrated in this work on six non-biological data. [ABSTRACT FROM AUTHOR]

Background A laboratory-free test for assessing recovery from pulmonary tuberculosis (TB) would be extremely beneficial in regions of the world where laboratory facilities are lacking. Our hypothesis is that analysis of cough sound recordings may provide such a test. In the current paper, we present validation of a cough analysis tool. Methodology/Principal Findings Cough data was collected from a cohort of TB patients in Lima, Peru and 25.5 hours of recordings were manually annotated by clinical staff. Analysis software was developed and validated by comparison to manual scoring. Because many patients cough in bursts, coughing was characterized in terms of cough epochs. Our software correctly detects 75.5% of cough episodes with a specificity of 99.6% (comparable to past results using the same definition) and a median false positive rate of 4 false positives/hour, due to the noisy, real-world nature of our dataset. We then manually review detected coughs to eliminate false positives, in effect using the algorithm as a pre-screening tool that reduces reviewing time to roughly 5% of the recording length. This cough analysis approach provides a foundation to support larger-scale studies of coughing rates over time for TB patients undergoing treatment. [ABSTRACT FROM AUTHOR]

Background: Consortia of microorganisms, commonly known as biofilms, are attracting much attention from the scientific community due to their impact in human activity. As biofilm research grows to be a data-intensive discipline, the need for suitable bioinformatics approaches becomes compelling to manage and validate individual experiments, and also execute inter-laboratory large-scale comparisons. However, biofilm data is widespread across ad hoc, non-standardized individual files and, thus, data interchange among researchers, or any attempt of cross-laboratory experimentation or analysis, is hardly possible or even attempted. Methodology/Principal Findings: This paper presents BiofOmics, the first publicly accessible Web platform specialized in the management and analysis of data derived from biofilm high-throughput studies. The aim is to promote data interchange across laboratories, implementing collaborative experiments, and enable the development of bioinformatics tools in support of the processing and analysis of the increasing volumes of experimental biofilm data that are being generated. BiofOmics' data deposition facility enforces data structuring and standardization, supported by controlled vocabulary. Researchers are responsible for the description of the experiments, their results and conclusions. BiofOmics' curators interact with submitters only to enforce data structuring and the use of controlled vocabulary. Then, BiofOmics' search facility makes publicly available the profile and data associated with a submitted study so that any researcher can profit from these standardization efforts to compare similar studies, generate new hypotheses to be tested or even extend the conditions experimented in the study. Significance: BiofOmics' novelty lies in its support to standardized data deposition, the availability of computerizable data files and the free-of-charge dissemination of biofilm studies across the community. Hopefully, this will open promising research possibilities, namely the comparison of results between different laboratories, the reproducibility of methods within and between laboratories, and the development of guidelines and standardized protocols for biofilm formation operating procedures and analytical methods. [ABSTRACT FROM AUTHOR]

In Positron Emission Tomography (PET), an optimal estimate of the radioactivity concentration is obtained from the measured emission data under certain criteria. So far, all the well-known statistical reconstruction algorithms require exactly known system probability matrix a priori, and the quality of such system model largely determines the quality of the reconstructed images. In this paper, we propose an algorithm for PET image reconstruction for the real world case where the PET system model is subject to uncertainties. The method counts PET reconstruction as a regularization problem and the image estimation is achieved by means of an uncertainty weighted least squares framework. The performance of our work is evaluated with the Shepp-Logan simulated and real phantom data, which demonstrates significant improvements in image quality over the least squares reconstruction efforts. [ABSTRACT FROM AUTHOR]

Motivation: The identification of robust lists of molecular biomarkers related to a disease is a fundamental step for early diagnosis and treatment. However, methodologies for the discovery of biomarkers using microarray data often provide results with limited overlap. These differences are imputable to 1) dataset size (few subjects with respect to the number of features); 2) heterogeneity of the disease; 3) heterogeneity of experimental protocols and computational pipelines employed in the analysis. In this paper, we focus on the first two issues and assess, both on simulated (through an in silico regulation network model) and real clinical datasets, the consistency of candidate biomarkers provided by a number of different methods. Methods: We extensively simulated the effect of heterogeneity characteristic of complex diseases on different sets of microarray data. Heterogeneity was reproduced by simulating both intrinsic variability of the population and the alteration of regulatory mechanisms. Population variability was simulated by modeling evolution of a pool of subjects; then, a subset of them underwent alterations in regulatory mechanisms so as to mimic the disease state. Results: The simulated data allowed us to outline advantages and drawbacks of different methods across multiple studies and varying number of samples and to evaluate precision of feature selection on a benchmark with known biomarkers. Although comparable classification accuracy was reached by different methods, the use of external cross-validation loops is helpful in finding features with a higher degree of precision and stability. Application to real data confirmed these results. [ABSTRACT FROM AUTHOR]

Meta-analyses play an important role in synthesizing evidence from diverse studies and datasets that address similar questions. A major obstacle for meta-analyses arises from biases in reporting. In particular, it is speculated that findings which do not achieve formal statistical significance are less likely reported than statistically significant findings. Moreover, the patterns of bias can be complex and may also depend on the timing of the research results and their relationship with previously published work. In this paper, we present an approach that is specifically designed to analyze large-scale datasets on published results. Such datasets are currently emerging in diverse research fields, particularly in molecular medicine. We use our approach to investigate a dataset on Alzheimer's disease (AD) that covers 1167 results from case-control studies on 102 genetic markers. We observe that initial studies on a genetic marker tend to be substantially more biased than subsequent replications. The chances for initial, statistically non-significant results to be published are estimated to be about 44% (95% CI, 32% to 63%) relative to statistically significant results, while statistically non-significant replications have almost the same chance to be published as statistically significant replications (84%; 95% CI, 66% to 107%). Early replications tend to be biased against initial findings, an observation previously termed Proteus phenomenon: The chances for nonsignificant studies going in the same direction as the initial result are estimated to be lower than the chances for nonsignificant studies opposing the initial result (73%; 95% CI, 55% to 96%). Such dynamic patters in bias are difficult to capture by conventional methods, where typically simple publication bias is assumed to operate. Our approach captures and corrects for complex dynamic patterns of bias, and thereby helps generating conclusions from published results that are more robust against the presence of different coexisting types of selective reporting. [ABSTRACT FROM AUTHOR]

Background: Many journals now require authors share their data with other investigators, either by depositing the data in a public repository or making it freely available upon request. These policies are explicit, but remain largely untested. We sought to determine how well authors comply with such policies by requesting data from authors who had published in one of two journals with clear data sharing policies. Methods and Findings: We requested data from ten investigators who had published in either PLoS Medicine or PLoS Clinical Trials. All responses were carefully documented. In the event that we were refused data, we reminded authors of the journal's data sharing guidelines. If we did not receive a response to our initial request, a second request was made. Following the ten requests for raw data, three investigators did not respond, four authors responded and refused to share their data, two email addresses were no longer valid, and one author requested further details. A reminder of PLoS's explicit requirement that authors share data did not change the reply from the four authors who initially refused. Only one author sent an original data set. Conclusions: We received only one of ten raw data sets requested. This suggests that journal policies requiring data sharing do not lead to authors making their data sets available to independent investigators. [ABSTRACT FROM AUTHOR]

Social network analysis has long been an untiring topic of sociology. However, until the era of information technology, the availability of data, mainly collected by the traditional method of personal survey, was highly limited and prevented large scale analysis. Recently, the exploding amount of automatically generated data has completely changed the pattern of research. For instance, the enormous amount of data from so-called high-throughput biological experiments has introduced a systematic or network viewpoint to traditional biology. Then, is ''high-throughput'' sociological data generation possible? Google, which has become one of the most influential symbols of the new Internet paradigm within the last ten years, might provide torrents of data sources for such study in this (now and forthcoming) digital era. We investigate social networks between people by extracting information on the Web and introduce new tools of analysis of such networks in the context of statistical physics of complex systems or socio-physics. As a concrete and illustrative example, the members of the 109th United States Senate are analyzed and it is demonstrated that the methods of construction and analysis are applicable to various other weighted networks. [ABSTRACT FROM AUTHOR]

Both sharing and using open research data have the revolutionary potentials for forwarding scientific advancement. Although previous research gives insight into researchers' drivers and inhibitors for sharing and using open research data, both these drivers and inhibitors have not yet been integrated via a thematic analysis and a theoretical argument is lacking. This study's purpose is to systematically review the literature on individual researchers' drivers and inhibitors for sharing and using open research data. This study systematically analyzed 32 open data studies (published between 2004 and 2019 inclusively) and elicited drivers plus inhibitors for both open research data sharing and use in eleven categories total that are: 'the researcher's background', 'requirements and formal obligations', 'personal drivers and intrinsic motivations', 'facilitating conditions', 'trust', 'expected performance', 'social influence and affiliation', 'effort', 'the researcher's experience and skills', 'legislation and regulation', and 'data characteristics.' This study extensively discusses these categories, along with argues how such categories and factors are connected using a thematic analysis. Also, this study discusses several opportunities for altogether applying, extending, using, and testing theories in open research data studies. With such discussions, an overview of identified categories and factors can be further applied to examine both researchers' drivers and inhibitors in different research disciplines, such as those with low rates of data sharing and use versus disciplines with high rates of data sharing plus use. What's more, this study serves as a first vital step towards developing effective incentives for both open data sharing and use behavior. [ABSTRACT FROM AUTHOR]

Background: Funding agencies and research journals are increasingly demanding that researchers share their data in public repositories. Despite these requirements, researchers still withhold data, refuse to share, and deposit data that lacks annotation. We conducted a meta-synthesis to examine the views, perspectives, and experiences of academic researchers on data sharing and reuse of research data. Methods: We searched the published and unpublished literature for studies on data sharing by researchers in academic institutions. Two independent reviewers screened citations and abstracts, then full-text articles. Data abstraction was performed independently by two investigators. The abstracted data was read and reread in order to generate codes. Key concepts were identified and thematic analysis was used for data synthesis. Results: We reviewed 2005 records and included 45 studies along with 3 companion reports. The studies were published between 2003 and 2018 and most were conducted in North America (60%) or Europe (17%). The four major themes that emerged were data integrity, responsible conduct of research, feasibility of sharing data, and value of sharing data. Researchers lack time, resources, and skills to effectively share their data in public repositories. Data quality is affected by this, along with subjective decisions around what is considered to be worth sharing. Deficits in infrastructure also impede the availability of research data. Incentives for sharing data are lacking. Conclusion: Researchers lack skills to share data in a manner that is efficient and effective. Improved infrastructure support would allow them to make data available quickly and seamlessly. The lack of incentives for sharing research data with regards to academic appointment, promotion, recognition, and rewards need to be addressed. [ABSTRACT FROM AUTHOR]

Determining intrinsic number of clusters in a multidimensional dataset is a commonly encountered problem in exploratory data analysis. Unsupervised clustering algorithms often rely on specification of cluster number as an input parameter. However, this is typically not known a priori. Many methods have been proposed to estimate cluster number, including statistical and information-theoretic approaches such as the gap statistic, but these methods are not always reliable when applied to non-normally distributed datasets containing outliers or noise. In this study, I propose a novel method called hierarchical linkage regression, which uses regression to estimate the intrinsic number of clusters in a multidimensional dataset. The method operates on the hypothesis that the organization of data into clusters can be inferred from the hierarchy generated by partitioning the dataset, and therefore does not directly depend on the specific values of the data or their distribution, but on their relative ranking within the partitioned set. Moreover, the technique does not require empirical data to train on, but can use synthetic data generated from random distributions to fit regression coefficients. The trained hierarchical linkage regression model is able to infer cluster number in test datasets of varying complexity and differing distributions, for image, text and numeric data, using the same regression model without retraining. The method performs favourably against other cluster number estimation techniques, and is also robust to parameter changes, as demonstrated by sensitivity analysis. The apparent robustness and generalizability of hierarchical linkage regression make it a promising tool for unsupervised exploratory data analysis and discovery. [ABSTRACT FROM AUTHOR]

Introduction: The digitalization of medicine has led to a considerable growth of heterogeneous health datasets, which could improve healthcare research if integrated into the clinical life cycle. This process requires, amongst other things, the harmonization of these datasets, which is a prerequisite to improve their quality, re-usability and interoperability. However, there is a wide range of factors that either hinder or favor the harmonized collection, sharing and linkage of health data. Objective: This systematic review aims to identify barriers and facilitators to health data harmonization—including data sharing and linkage—by a comparative analysis of studies from Denmark and Switzerland. Methods: Publications from PubMed, Web of Science, EMBASE and CINAHL involving cross-institutional or cross-border collection, sharing or linkage of health data from Denmark or Switzerland were searched to identify the reported barriers and facilitators to data harmonization. Results: Of the 345 projects included, 240 were single-country and 105 were multinational studies. Regarding national projects, a Swiss study reported on average more barriers and facilitators than a Danish study. Barriers and facilitators of a technical nature were most frequently reported. Conclusion: This systematic review gathered evidence from Denmark and Switzerland on barriers and facilitators concerning data harmonization, sharing and linkage. Barriers and facilitators were strictly interrelated with the national context where projects were carried out. Structural changes, such as legislation implemented at the national level, were mirrored in the projects. This underlines the impact of national strategies in the field of health data. Our findings also suggest that more openness and clarity in the reporting of both barriers and facilitators to data harmonization constitute a key element to promote the successful management of new projects using health data and the implementation of proper policies in this field. Our study findings are thus meaningful beyond these two countries. [ABSTRACT FROM AUTHOR]

Trust is praised by many social scientists as the foundation of functioning social systems owing to its assumed connection to cooperative behavior. The existence of such a link is still subject to debate. In the present study, we first highlight important conceptual issues within this debate. Second, we examine previous evidence, highlighting several issues. Third, we present findings from an original experiment, in which we tried to identify a “real” situation that allowed us to measure both trust and cooperation. People’s expectations and behavior when they decide to share (or not) their data represents such a situation, and we make use of corresponding data. We found that there is no relationship between trust and cooperation. This non-relationship may be rationalized in different ways which, in turn, provides important lessons for the study of the trust—behavior nexus beyond the particular situation we study empirically. [ABSTRACT FROM AUTHOR]

Road traffic congestion continues to manifest and propagate in cities around the world. The recent technological advancements in intelligent traveler information have a strong influence on the route choice behavior of drivers by enabling them to be more flexible in selecting their routes. Measuring traffic congestion in a city, understanding its spatial dispersion, and investigating whether the congestion patterns are stable (temporally, such as on a day-to-day basis) are critical to developing effective traffic management strategies. In this study, with the help of Google Maps API, we gather traffic speed data of 29 cities across the world over a 40-day period. We present generalized congestion and network stability metrics to compare congestion levels between these cities. We find that (a) traffic congestion is related to macroeconomic characteristics such as per capita income and population density of these cities, (b) congestion patterns are mostly stable on a day-to-day basis, and (c) the rate of spatial dispersion of congestion is smaller in congested cities, i.e. the spatial heterogeneity is less sensitive to increase in delays. This study compares the traffic conditions across global cities on a common datum using crowdsourced data which is becoming readily available for research purposes. This information can potentially assist practitioners to tailor macroscopic network congestion and reliability management policies. The comparison of different cities can also lead to benchmarking and standardization of the policies that have been used to date. [ABSTRACT FROM AUTHOR]

Health management information system (HMIS) data are important for guiding the attainment of health targets in low- and middle-income countries. However, the quality of HMIS data is often poor. High-quality information is especially important for populations experiencing high burdens of disease and mortality, such as pregnant women, newborns, and children. The purpose of this study was to assess the quality of maternal and child health (MCH) data collected through the Ethiopian Ministry of Health’s HMIS in three districts of Jimma Zone, Oromiya Region, Ethiopia over a 12-month period from July 2014 to June 2015. Considering data quality constructs from the World Health Organization’s data quality report card, we appraised the completeness, timeliness, and internal consistency of eight key MCH indicators collected for all the primary health care units (PHCUs) located within three districts of Jimma Zone (Gomma, Kersa and Seka Chekorsa). We further evaluated the agreement between MCH service coverage estimates from the HMIS and estimates obtained from a population-based cross-sectional survey conducted with 3,784 women who were pregnant in the year preceding the survey, using Pearson correlation coefficients, intraclass correlation coefficients (ICC), and Bland-Altman plots. We found that the completeness and timeliness of facility reporting were highest in Gomma (75% and 70%, respectively) and lowest in Kersa (34% and 32%, respectively), and observed very few zero/missing values and moderate/extreme outliers for each MCH indicator. We found that the reporting of MCH indicators improved over time for all PHCUs, however the internal consistency between MCH indicators was low for several PHCUs. We found poor agreement between MCH estimates obtained from the HMIS and the survey, indicating that the HMIS may over-report the coverage of key MCH services, namely, antenatal care, skilled birth attendance and postnatal care. The quality of MCH data within the HMIS at the zonal level in Jimma, Ethiopia, could be improved to inform MCH research and programmatic efforts. [ABSTRACT FROM AUTHOR]

The McGurk effect is a classic audiovisual speech illusion in which discrepant auditory and visual syllables can lead to a fused percept (e.g., an auditory /bɑ/ paired with a visual /gɑ/ often leads to the perception of /dɑ/). The McGurk effect is robust and easily replicated in pooled group data, but there is tremendous variability in the extent to which individual participants are susceptible to it. In some studies, the rate at which individuals report fusion responses ranges from 0% to 100%. Despite its widespread use in the audiovisual speech perception literature, the roots of the wide variability in McGurk susceptibility are largely unknown. This study evaluated whether several perceptual and cognitive traits are related to McGurk susceptibility through correlational analyses and mixed effects modeling. We found that an individual’s susceptibility to the McGurk effect was related to their ability to extract place of articulation information from the visual signal (i.e., a more fine-grained analysis of lipreading ability), but not to scores on tasks measuring attentional control, processing speed, working memory capacity, or auditory perceptual gradiency. These results provide support for the claim that a small amount of the variability in susceptibility to the McGurk effect is attributable to lipreading skill. In contrast, cognitive and perceptual abilities that are commonly used predictors in individual differences studies do not appear to underlie susceptibility to the McGurk effect. [ABSTRACT FROM AUTHOR]

Background: Many national cardiovascular disease (CVD) risk factor management guidelines now recommend that drug treatment decisions should be informed primarily by patients’ multi-variable predicted risk of CVD, rather than on the basis of single risk factor thresholds. To investigate the potential impact of treatment guidelines based on CVD risk thresholds at a national level requires individual level data representing the multi-variable CVD risk factor profiles for a country’s total adult population. As these data are seldom, if ever, available, we aimed to create a synthetic population, representing the joint CVD risk factor distributions of the adult New Zealand population. Methods and results: A synthetic population of 2,451,278 individuals, representing the actual age, gender, ethnicity and social deprivation composition of people aged 30–84 years who completed the 2013 New Zealand census was generated using Monte Carlo sampling. Each ‘synthetic’ person was then probabilistically assigned values of the remaining cardiovascular disease (CVD) risk factors required for predicting their CVD risk, based on data from the national census national hospitalisation and drug dispensing databases and a large regional cohort study, using Monte Carlo sampling and multiple imputation. Where possible, the synthetic population CVD risk distributions for each non-demographic risk factor were validated against independent New Zealand data sources. Conclusions: We were able to develop a synthetic national population with realistic multi-variable CVD risk characteristics. The construction of this population is the first step in the development of a micro-simulation model intended to investigate the likely impact of a range of national CVD risk management strategies that will inform CVD risk management guideline updates in New Zealand and elsewhere. [ABSTRACT FROM AUTHOR]

Utilizing data from published tuberculosis (TB) genome-wide association studies (GWAS), we use a bioinformatics pipeline to detect all polymorphisms in linkage disequilibrium (LD) with variants previously implicated in TB disease susceptibility. The probability that these variants had a predicted regulatory function was estimated using RegulomeDB and Ensembl’s Variant Effect Predictor. Subsequent genotyping of these 133 predicted regulatory polymorphisms was performed in 400 admixed South African TB cases and 366 healthy controls in a population-based case-control association study to fine-map the causal variant. We detected associations between tuberculosis susceptibility and six intronic polymorphisms located in MARCO, IFNGR2, ASHAS2, ACACA, NISCH and TLR10. Our post-GWAS approach demonstrates the feasibility of combining multiple TB GWAS datasets with linkage information to identify regulatory variants associated with this infectious disease. [ABSTRACT FROM AUTHOR]

Proteogenomic approaches have gained increasing popularity, however it is still difficult to integrate mass spectrometry identifications with genomic data due to differing data formats. To address this difficulty, we introduce iPiG as a tool for the integration of peptide identifications from mass spectrometry experiments into existing genome browser visualizations. Thereby, the concurrent analysis of proteomic and genomic data is simplified and proteomic results can directly be compared to genomic data. iPiG is freely available from https://sourceforge.net/projects/ipig/. It is implemented in Java and can be run as a stand-alone tool with a graphical user-interface or integrated into existing workflows. Supplementary data are available at PLOS ONE online. [ABSTRACT FROM AUTHOR]

Increasing public interest in science information in a digital and 2.0 science era promotes a dramatically, rapid and deep change in science itself. The emergence and expansion of new technologies and internet-based tools is leading to new means to improve scientific methodology and communication, assessment, promotion and certification. It allows methods of acquisition, manipulation and storage, generating vast quantities of data that can further facilitate the research process. It also improves access to scientific results through information sharing and discussion. Content previously restricted only to specialists is now available to a wider audience. This context requires new management systems to make scientific knowledge more accessible and useable, including new measures to evaluate the reach of scientific information. The new science and research quality measures are strongly related to the new online technologies and services based in social media. Tools such as blogs, social bookmarks and online reference managers, Twitter and others offer alternative, transparent and more comprehensive information about the active interest, usage and reach of scientific publications. Another of these new filters is the Research Blogging platform, which was created in 2007 and now has over 1,230 active blogs, with over 26,960 entries posted about peer-reviewed research on subjects ranging from Anthropology to Zoology. This study takes a closer look at RB, in order to get insights into its contribution to the rapidly changing landscape of scientific communication. [ABSTRACT FROM AUTHOR]

A motif in a network is a connected graph that occurs significantly more frequently as an induced subgraph than would be expected in a similar randomized network. By virtue of being atypical, it is thought that motifs might play a more important role than arbitrary subgraphs. Recently, a flurry of advances in the study of network motifs has created demand for faster computational means for identifying motifs in increasingly larger networks. Motif detection is typically performed by enumerating subgraphs in an input network and in an ensemble of comparison networks; this poses a significant computational problem. Classifying the subgraphs encountered, for instance, is typically performed using a graph canonical labeling package, such as Nauty, and will typically be called billions of times. In this article, we describe an implementation of a network motif detection package, which we call NetMODE. NetMODE can only perform motif detection for k-node subgraphs when k⩽6, but does so without the use of Nauty. To avoid using Nauty, NetMODE has an initial pretreatment phase, where k-node graph data is stored in memory (k⩽5). For k=6 we take a novel approach, which relates to the Reconstruction Conjecture for directed graphs. We find that NetMODE can perform up to around 30 times faster than its predecessors when k⩽5 and up to around 20 times faster when k=6 (the exact improvement varies considerably). NetMODE also (a) includes a method for generating comparison graphs uniformly at random, (b) can interface with external packages (e.g. R), and (c) can utilize multi-core architectures. NetMODE is available from netmode.sf.net. [ABSTRACT FROM AUTHOR]

Background: The emergence of next generation sequencing (NGS) has provided the means for rapid and high throughput sequencing and data generation at low cost, while concomitantly creating a new set of challenges. The number of available assembled microbial genomes continues to grow rapidly and their quality reflects the quality of the sequencing technology used, but also of the analysis software employed for assembly and annotation. Methodology/Principal Findings: In this work, we have explored the quality of the microbial draft genomes across various sequencing technologies. We have compared the draft and finished assemblies of 133 microbial genomes sequenced at the Department of Energy-Joint Genome Institute and finished at the Los Alamos National Laboratory using a variety of combinations of sequencing technologies, reflecting the transition of the institute from Sanger-based sequencing platforms to NGS platforms. The quality of the public assemblies and of the associated gene annotations was evaluated using various metrics. Results obtained with the different sequencing technologies, as well as their effects on downstream processes, were analyzed. Our results demonstrate that the Illumina HiSeq 2000 sequencing system, the primary sequencing technology currently used for de novo genome sequencing and assembly at JGI, has various advantages in terms of total sequence throughput and cost, but it also introduces challenges for the downstream analyses. In all cases assembly results although on average are of high quality, need to be viewed critically and consider sources of errors in them prior to analysis. Conclusion: These data follow the evolution of microbial sequencing and downstream processing at the JGI from draft genome sequences with large gaps corresponding to missing genes of significant biological role to assemblies with multiple small gaps (Illumina) and finally to assemblies that generate almost complete genomes (Illumina+PacBio) [ABSTRACT FROM AUTHOR]

Sequence-specific RNA binding proteins can induce the degradation of mRNAs through their ability to recruit proteins that trigger transcript destabilization. For example, Vts1p, the S. cerevisiae member of the Smaug family of RNA binding proteins, is thought to induce transcript decay by recruiting the Ccr4p-Pop2p-Not deadenylase complex to target mRNAs. The resulting deadenylation triggers transcript decapping followed by 5'-to-3' exonucleolytic decay. Here we show that the eIF4E-binding protein, Eap1p, is required for efficient degradation of Vts1p target transcripts and that this role involves the ability of Eap1p to interact with eIF4E. Eap1p does not stimulate deadenylation of Vts1p target transcripts but is instead involved in decapping. Eap1p interacts with Vts1p and mediates an indirect interaction between Vts1p and eIF4E. Taken together these data suggest a model whereby the interaction of Vts1p with Eap1p at target mRNAs stimulates decapping. [ABSTRACT FROM AUTHOR]

Background: The interaction between loci to affect phenotype is called epistasis. It is strict epistasis if no proper subset of the interacting loci exhibits a marginal effect. For many diseases, it is likely that unknown epistatic interactions affect disease susceptibility. A difficulty when mining epistatic interactions from high-dimensional datasets concerns the curse of dimensionality. There are too many combinations of SNPs to perform an exhaustive search. A method that could locate strict epistasis without an exhaustive search can be considered the brass ring of methods for analyzing high-dimensional datasets. Methodology/Findings: A SNP pattern is a Bayesian network representing SNP-disease relationships. The Bayesian score for a SNP pattern is the probability of the data given the pattern, and has been used to learn SNP patterns. We identified a bound for the score of a SNP pattern. The bound provides an upper limit on the Bayesian score of any pattern that could be obtained by expanding a given pattern. We felt that the bound might enable the data to say something about the promise of expanding a 1-SNP pattern even when there are no marginal effects. We tested the bound using simulated datasets and semi-synthetic high-dimensional datasets obtained from GWAS datasets. We found that the bound was able to dramatically reduce the search time for strict epistasis. Using an Alzheimer's dataset, we showed that it is possible to discover an interaction involving the APOE gene based on its score because of its large marginal effect, but that the bound is most effective at discovering interactions without marginal effects. Conclusions/Significance: We conclude that the bound appears to ameliorate the curse of dimensionality in high- dimensional datasets. This is a very consequential result and could be pivotal in our efforts to reveal the dark matter of genetic disease risk from high-dimensional datasets. [ABSTRACT FROM AUTHOR]

Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets. [ABSTRACT FROM AUTHOR]

Many important questions in biology are, fundamentally, comparative, and this extends to our analysis of a growing number of sequenced genomes. Existing genomic analysis tools are often organized around literal views of genomes as linear strings. Even when information is highly condensed, these views grow cumbersome as larger numbers of genomes are added. Data aggregation and summarization methods from the field of visual analytics can provide abstracted comparative views, suitable for sifting large multi-genome datasets to identify critical similarities and differences. We introduce a software system for visual analysis of comparative genomics data. The system automates the process of data integration, and provides the analysis platform to identify and explore features of interest within these large datasets. GenoSets borrows techniques from business intelligence and visual analytics to provide a rich interface of interactive visualizations supported by a multi-dimensional data warehouse. In GenoSets, visual analytic approaches are used to enable querying based on orthology, functional assignment, and taxonomic or user-defined groupings of genomes. GenoSets links this information together with coordinated, interactive visualizations for both detailed and high-level categorical analysis of summarized data. GenoSets has been designed to simplify the exploration of multiple genome datasets and to facilitate reasoning about genomic comparisons. Case examples are included showing the use of this system in the analysis of 12 Brucella genomes. GenoSets software and the case study dataset are freely available at http://genosets.uncc.edu. We demonstrate that the integration of genomic data using a coordinated multiple view approach can simplify the exploration of large comparative genomic data sets, and facilitate reasoning about comparisons and features of interest. [ABSTRACT FROM AUTHOR]

Spectral content in a physiological dataset of finite size has the potential to produce spurious measures of coherence. This is especially true for electroencephalography (EEG) during general anesthesia because of the significant alteration of the power spectrum. In this study we quantitatively evaluated the genuine and spurious phase synchronization strength (PSS) of EEG during consciousness, general anesthesia, and recovery. A computational approach based on the randomized data method was used for evaluating genuine and spurious PSS. The validity of the method was tested with a simulated dataset. We applied this method to the EEG of normal subjects undergoing general anesthesia and investigated the finite size effects of EEG references, data length and spectral content on phase synchronization. The most influential factor for genuine PSS was the type of EEG reference; the most influential factor for spurious PSS was the spectral content. Genuine and spurious PSS showed characteristic temporal patterns for each frequency band across consciousness and anesthesia. Simultaneous measurement of both genuine and spurious PSS during general anesthesia is necessary in order to avoid incorrect interpretations regarding states of consciousness. [ABSTRACT FROM AUTHOR]

The common approach to SNP genotyping is to use (model-based) clustering per individual SNP, on a set of arrays. Genotyping all SNPs on a single array is much more attractive, in terms of flexibility, stability and applicability, when developing new chips. A new semi-parametric method, named SCALA, is proposed. It is based on a mixture model using semi-parametric log-concave densities. Instead of using the raw data, the mixture is fitted on a two-dimensional histogram, thereby making computation time almost independent of the number of SNPs. Furthermore, the algorithm is effective in low-MAF situations. Comparisons between SCALA and CRLMM on HapMap genotypes show very reliable calling of single arrays. Some heterozygous genotypes from HapMap are called homozygous by SCALA and to lesser extent by CRLMM too. Furthermore, HapMap's NoCalls (NN) could be genotyped by SCALA, mostly with high probability. The software is available as R scripts from the website www.math.leidenuniv.nl/~rrippe. [ABSTRACT FROM AUTHOR]

Background: There are several types of tobacco control interventions/policies which can change future smoking exposure. The most basic intervention types are 1) smoking cessation interventions 2) preventing smoking initiation and 3) implementation of a nationwide policy affecting quitters and starters simultaneously. The possibility for dynamic quantification of such different interventions is key for comparing the timing and size of their effects. Methods and Results: We developed a software tool, DYNAMO-HIA, which allows for a quantitative comparison of the health impact of different policy scenarios. We illustrate the outcomes of the tool for the three typical types of tobacco control interventions if these were applied in the Netherlands. The tool was used to model the effects of different types of smoking interventions on future smoking prevalence and on health outcomes, comparing these three scenarios with the business-as-usual scenario. The necessary data input was obtained from the DYNAMO-HIA database which was assembled as part of this project. All smoking interventions will be effective in the long run. The population-wide strategy will be most effective in both the short and long term. The smoking cessation scenario will be second-most effective in the short run, though in the long run the smoking initiation scenario will become almost as effective. Interventions aimed at preventing the initiation of smoking need a long time horizon to become manifest in terms of health effects. The outcomes strongly depend on the groups targeted by the intervention. Conclusion: We calculated how much more effective the population-wide strategy is, in both the short and long term, compared to quit smoking interventions and measures aimed at preventing the initiation of smoking. By allowing a great variety of user-specified choices, the DYNAMO-HIA tool is a powerful instrument by which the consequences of different tobacco control policies and interventions can be assessed. [ABSTRACT FROM AUTHOR]

The ability to generate whole genome data is rapidly becoming commoditized. For example, a mammalian sized genome (∼3Gb) can now be sequenced using approximately ten lanes on an Illumina HiSeq 2000. Since lanes from different runs are often combined, verifying that each lane in a genome's build is from the same sample is an important quality control. We sought to address this issue in a post hoc bioinformatic manner, instead of using upstream sample or ''barcode'' modifications. We rely on the inherent small differences between any two individuals to show that genotype concordance rates can be effectively used to test if any two lanes of HiSeq 2000 data are from the same sample. As proof of principle, we use recent data from three different human samples generated on this platform. We show that the distributions of concordance rates are non-overlapping when comparing lanes from the same sample versus lanes from different samples. Our method proves to be robust even when different numbers of reads are analyzed. Finally, we provide a straightforward method for determining the gender of any given sample. Our results suggest that examining the concordance of detected genotypes from lanes purported to be from the same sample is a relatively simple approach for confirming that combined lanes of data are of the same identity and quality. [ABSTRACT FROM AUTHOR]

Introduction: Difficulties with visual perception (VP) are often described in children with neurological or developmental problems. However, there are few data regarding the range of visual perceptual abilities in populations of normal children, or on the impact of these abilities on children's day-to-day functioning. Methods: Data were obtained for 4512 participants in an ongoing birth cohort study (Avon Longitudinal Study of Parents and Children; ALSPAC). The children's mothers responded to questions designed to elicit indications of visual perceptual difficulties or immaturity, when their children were aged 13 years. We examined associations with standardised school test results in reading and in mathematics at age 13-14 years (SATS-KS3), accounting for potential confounders including IQ. Results: Three underlying factors explained half the variance in the VP question responses. These correlated best with questions on interpreting cluttered scenes; guidance of movement and face recognition. The adjusted parameter estimates (95% CI) for the cluttered-scenes factor (0.05; 0.02 to 0.08; p<0.001) suggested positive associations with the reading test results whilst that for the guidance-of-movement factor (0.03; 0.00 to 0.06; p = 0.026) suggested positive association with the mathematics results. The raw scores were associated with both test results. Discussion: VP abilities were widely distributed in this sample of 13-year old children. Lower levels of VP function were associated with under-achievement in reading and in mathematics. Simple interventions can help children with VP difficulties, so research is needed into practicable, cost-effective strategies for identification and assessment, so that support can be targeted appropriately. [ABSTRACT FROM AUTHOR]

The present study reports timed norms for 435 object pictures in Mandarin Chinese. These data include naming latency, name agreement, concept agreement, word length, and age of acquisition (AoA) based on children's naming and adult ratings, and several other adult ratings of concept familiarity, subjective word frequency, image agreement, image variability, and visual complexity. Furthermore, we examined factors that influence the naming latencies of the pictures. The results show that concept familiarity, AoA, concept agreement, name agreement, and image agreement are significant predictors of naming latencies, whereas subjective word frequency is not a reliable determinant. These results are discussed in light of picture naming data in other languages. An item-based index for the norms is provided in the Table S1. [ABSTRACT FROM AUTHOR]

Background: The diagnostic approach to dizzy, older patients is not straightforward as many organ systems can be involved and evidence for diagnostic strategies is lacking. A first differentiation in diagnostic subtypes or profiles may guide the diagnostic process of dizziness and can serve as a classification system in future research. In the literature this has been done, but based on pathophysiological reasoning only. Objective: To establish a classification of diagnostic profiles of dizziness based on empirical data. Design: Cross-sectional study. Participants and Setting: 417 consecutive patients of 65 years and older presenting with dizziness to 45 primary care physicians in the Netherlands from July 2006 to January 2008. Methods: We performed tests, including patient history, and physical and additional examination, previously selected by an international expert panel and based on an earlier systematic review. We used the results of these tests in a principal component analysis for exploration, data-reduction and finally differentiation into diagnostic dizziness profiles. Results: Demographic data and the results of the tests yielded 221 variables, of which 49 contributed to the classification of dizziness into six diagnostic profiles, that may be named as follows: ''frailty'', ''psychological'', ''cardiovascular'', ''presyncope'', ''non-specific dizziness'' and ''ENT''. These explained 32% of the variance. Conclusions: Empirically identified components classify dizziness into six profiles. This classification takes into account the heterogeneity and multicausality of dizziness and may serve as starting point for research on diagnostic strategies and can be a first step in an evidence based diagnostic approach of dizzy older patients. [ABSTRACT FROM AUTHOR]

Background: How to extract useful information from complex biological networks is a major goal in many fields, especially in genomics and proteomics. We have shown in several works that iterative hierarchical clustering, as implemented in the UVCluster program, is a powerful tool to analyze many of those networks. However, the amount of computation time required to perform UVCluster analyses imposed significant limitations to its use. Methodology/Principal Findings: We describe the suite Jerarca, designed to efficiently convert networks of interacting units into dendrograms by means of iterative hierarchical clustering. Jerarca is divided into three main sections. First, weighted distances among units are computed using up to three different approaches: a more efficient version of UVCluster and two new, related algorithms called RCluster and SCluster. Second, Jerarca builds dendrograms based on those distances, using well-known phylogenetic algorithms, such as UPGMA or Neighbor-Joining. Finally, Jerarca provides optimal partitions of the trees using statistical criteria based on the distribution of intra- and intercluster connections. Outputs compatible with the phylogenetic software MEGA and the Cytoscape package are generated, allowing the results to be easily visualized. Conclusions/Significance: The four main advantages of Jerarca in respect to UVCluster are: 1) Improved speed of a novel UVCluster algorithm; 2) Additional, alternative strategies to perform iterative hierarchical clustering; 3) Automatic evaluation of the hierarchical trees to obtain optimal partitions; and, 4) Outputs compatible with popular software such as MEGA and Cytoscape. [ABSTRACT FROM AUTHOR]

Successful predictions of peptide MHC binding typically require a large set of binding data for the specific MHC molecule that is examined. Structure based prediction methods promise to circumvent this requirement by evaluating the physical contacts a peptide can make with an MHC molecule based on the highly conserved 3D structure of peptide:MHC complexes. While several such methods have been described before, most are not publicly available and have not been independently tested for their performance. We here implemented and evaluated three prediction methods for MHC class II molecules: statistical potentials derived from the analysis of known protein structures; energetic evaluation of different peptide snapshots in a molecular dynamics simulation; and direct analysis of contacts made in known 3D structures of peptide:MHC complexes. These methods are ab initio in that they require structural data of the MHC molecule examined, but no specific peptide:MHC binding data. Moreover, these methods retain the ability to make predictions in a sufficiently short time scale to be useful in a real world application, such as screening a whole proteome for candidate binding peptides. A rigorous evaluation of each methods prediction performance showed that these are significantly better than random, but still substantially lower than the best performing sequence based class II prediction methods available. While the approaches presented here were developed independently, we have chosen to present our results together in order to support the notion that generating structure based predictions of peptide:MHC binding without using binding data is unlikely to give satisfactory results. [ABSTRACT FROM AUTHOR]

Background: The growth of sequencing-based Chromatin Immuno-Precipitation studies call for a more in-depth understanding of the nature of the technology and of the resultant data to reduce false positives and false negatives. Control libraries are typically constructed to complement such studies in order to mitigate the effect of systematic biases that might be present in the data. In this study, we explored multiple control libraries to obtain better understanding of what they truly represent. Methodology: First, we analyzed the genome-wide profiles of various sequencing-based libraries at a low resolution of 1 Mbp, and compared them with each other as well as against aCGH data. We found that copy number plays a major influence in both ChIP-enriched as well as control libraries. Following that, we inspected the repeat regions to assess the extent of mapping bias. Next, significantly tag-rich 5 kbp regions were identified and they were associated with various genomic landmarks. For instance, we discovered that gene boundaries were surprisingly enriched with sequenced tags. Further, profiles between different cell types were noticeably distinct although the cell types were somewhat related and similar. Conclusions: We found that control libraries bear traces of systematic biases. The biases can be attributed to genomic copy number, inherent sequencing bias, plausible mapping ambiguity, and cell-type specific chromatin structure. Our results suggest careful analysis of control libraries can reveal promising biological insights. [ABSTRACT FROM AUTHOR]

Allometric equations are widely used in many branches of biological science. The potential information content of the normalization constant b in allometric equations of the form Y=bXa has, however, remained largely neglected. To demonstrate the potential for utilizing this information, I generated a large number of artificial datasets that resembled those that are frequently encountered in biological studies, i.e., relatively small samples including measurement error or uncontrolled variation. The value of X was allowed to vary randomly within the limits describing different data ranges, and a was set to a fixed theoretical value. The constant b was set to a range of values describing the effect of a continuous environmental variable. In addition, a normally distributed random error was added to the values of both X and Y. Two different approaches were then used to model the data. The traditional approach estimated both a and b using a regression model, whereas an alternative approach set the exponent a at its theoretical value and only estimated the value of b. Both approaches produced virtually the same model fit with less than 0.3% difference in the coefficient of determination. Only the alternative approach was able to precisely reproduce the effect of the environmental variable, which was largely lost among noise variation when using the traditional approach. The results show how the value of b can be used as a source of valuable biological information if an appropriate regression model is selected. [ABSTRACT FROM AUTHOR]