Search

Cooperation among kin is common in animal societies. Kin groups may form by individuals directly discriminating relatives based on kin recognition cues, or form passively through natal philopatry and limited dispersal. We describe the genetic landscape for a primitively eusocial wasp, Polistes dominula, and ask whether individuals choose cooperative partners that are nearby and/or that are genetic relatives. Firstly, we genotyped an entire sub-population of 1361 wasps and found genetic structuring on an extremely fine scale: the probability of finding genetic relatives decreases exponentially within just a few meters of an individual’s nest. At the same time, however, we found a lack of genetic structuring between natural nest aggregations within the population. Secondly, in a separate dataset where ~2000 wasps were genotyped, we show that wasps forced experimentally to make a new nest choice tended to choose new nests near to their original nests, and that these nests tended to contain some full sisters. However, a significant fraction of wasps chose nests that did not contain sisters, despite sisters being present in nearby nests. Although we cannot rule out a role for direct kin recognition or natal nest-mate recognition, our data suggest that kin groups may form via a philopatric rule-of-thumb, whereby wasps simply select groups and nesting sites that are nearby. The result is that most subordinate helpers obtain indirect fitness benefits by breeding cooperatively. [ABSTRACT FROM AUTHOR]

Introduction: In this paper we perform a replication analysis of “Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial” by Sarah Baird and others published in “The Lancet” in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13–22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. Methods: We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. Results: The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. Conclusions: The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution. [ABSTRACT FROM AUTHOR]

This paper investigates a well-known complex combinatorial problem known as the vehicle routing problem with time windows (VRPTW). Unlike the standard vehicle routing problem, each customer in the VRPTW is served within a given time constraint. This paper solves the VRPTW using an improved artificial bee colony (IABC) algorithm. The performance of this algorithm is improved by a local optimization based on a crossover operation and a scanning strategy. Finally, the effectiveness of the IABC is evaluated on some well-known benchmarks. The results demonstrate the power of IABC algorithm in solving the VRPTW. [ABSTRACT FROM AUTHOR]

Classical null hypothesis significance tests are not appropriate in corpus linguistics, because the randomness assumption underlying these testing procedures is not fulfilled. Nevertheless, there are numerous scenarios where it would be beneficial to have some kind of test in order to judge the relevance of a result (e.g. a difference between two corpora) by answering the question whether the attribute of interest is pronounced enough to warrant the conclusion that it is substantial and not due to chance. In this paper, I outline such a test. [ABSTRACT FROM AUTHOR]

In this paper we investigate the changes in the functional connectivity intensity, and some related properties, in healthy people, across the life span and at resting state. For the explicit computation of the functional connectivity we exploit a recently proposed model, that bases not only on the correlations data provided by the acquisition equipment, but also on different parameters, such as the anatomical distances between nodes and their degrees. The leading purpose of the paper is to show that the proposed approach is able to recover the main aspects of resting state condition known from the available literature, as well as to suggest new insights, perspectives and speculations from a neurobiological point of view. Our study involves 133 subjects, both males and females of different ages, with no evidence of neurological diseases or systemic disorders. First, we show how the model applies to the sample, where the subjects are grouped into 28 different groups (14 of males and 14 of females), according to their age. This leads to the construction of two graphs (one for males and one for females), that can be realistically interpreted as representative of the neural network during the resting state. Second, following the idea that the brain network is better understood by focusing on specific nodes having a kind of centrality, we refine the two output graphs by introducing a new metric that favours the selection of nodes having higher degrees. As a third step, we extensively comment and discuss the obtained results. In particular, it is remarkable that, despite a great overlapping exists between the outcomes concerning males and females, some intriguing differences appear. This motivates a deeper local investigation, which represents the fourth part of the paper, carried out through a thorough statistical analysis. As a result, we are enabled to support that, for two special age groups, a few links contribute in differentiating the behaviour of males and females. In addition, we performed an average-based comparison between the proposed model and the traditional statistical correlation-based approach, then discussing and commenting the main outlined discrepancies. [ABSTRACT FROM AUTHOR]

The problem of finding an optimum within a set of possibilities that represent the varying successfulness of numerous subjects competing with one another is highly relevant in the field of ecosystem interactions. We propose a method for solving this problem by the application of the Nash equilibrium concept, which is frequently used in ecology. The proposed model is based on the transformation of the initial payoff vectors of subjects that interact in different situations into a statistical set of symmetrical game matrices that consist of permutations of payoff values. The equilibrium solution is expressed as values of the probability of Nash equilibrium occurrence with uniform distribution over all possible permutations based on uncertainty of positions of payoff values in the matrix. We assume that this equilibrium solution provides information on the distribution of the degree of stability among individual situations and interacting subjects. In this paper, we validate this assumption and demonstrate its application to a dataset that represents interspecies interactions in plant ecology. We propose that the use of the Nash equilibrium in the analysis of datasets formalized according to the Pareto optimality scheme is applicable in numerous other contexts. [ABSTRACT FROM AUTHOR]

Two critical tasks in multi-criteria group decision making (MCGDM) are to describe criterion values and to aggregate the described information to generate a ranking of alternatives. A flexible and superior tool for the first task is q-rung orthopair fuzzy number (qROFN) and an effective tool for the second task is aggregation operator. So far, nearly thirty different aggregation operators of qROFNs have been presented. Each operator has its distinctive characteristics and can work well for specific purpose. However, there is not yet an operator which can provide desirable generality and flexibility in aggregating criterion values, dealing with the heterogeneous interrelationships among criteria, and reducing the influence of extreme criterion values. To provide such an aggregation operator, Muirhead mean operator, power average operator, partitioned average operator, and Archimedean T-norm and T-conorm operations are concurrently introduced into q-rung orthopair fuzzy sets, and an Archimedean power partitioned Muirhead mean operator of qROFNs and its weighted form are presented and a MCGDM method based on the weighted operator is proposed in this paper. The generalised expressions of the two operators are firstly defined. Their properties are explored and proved and their specific expressions are constructed. On the basis of the specific expressions, a method for solving the MCGDM problems based on qROFNs is then designed. Finally, the feasibility and effectiveness of the method is demonstrated via a numerical example, a set of experiments, and qualitative and quantitative comparisons. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) affects millions of people and is a major rising problem in health care worldwide. Recent research suggests that AD could have different subtypes, presenting differences in how the disease develops. Characterizing those subtypes could be key to deepen the understanding of this complex disease. In this paper, we used a multivariate, non-supervised clustering method over blood-based markers to find subgroups of patients defined by distinctive blood marker profiles. Our analysis on ADNI database identified 4 possible subgroups, each with a different blood profile. More importantly, we show that subgroups with different profiles have a different relationship between brain phenotypes detected in magnetic resonance imaging and disease condition. [ABSTRACT FROM AUTHOR]

Objectives: Professional sporting organisations invest considerable resources collecting and analysing data in order to better understand the factors that influence performance. Recent advances in non-invasive technologies, such as global positioning systems (GPS), mean that large volumes of data are now readily available to coaches and sport scientists. However analysing such data can be challenging, particularly when sample sizes are small and data sets contain multiple highly correlated variables, as is often the case in a sporting context. Multicollinearity in particular, if not treated appropriately, can be problematic and might lead to erroneous conclusions. In this paper we present a novel ‘leave one variable out’ (LOVO) partial least squares correlation analysis (PLSCA) methodology, designed to overcome the problem of multicollinearity, and show how this can be used to identify the training load (TL) variables that influence most ‘end fitness’ in young rugby league players. Methods: The accumulated TL of sixteen male professional youth rugby league players (17.7 ± 0.9 years) was quantified via GPS, a micro-electrical-mechanical-system (MEMS), and players’ session-rating-of-perceived-exertion (sRPE) over a 6-week pre-season training period. Immediately prior to and following this training period, participants undertook a 30–15 intermittent fitness test (30-15IFT), which was used to determine a players ‘starting fitness’ and ‘end fitness’. In total twelve TL variables were collected, and these along with ‘starting fitness’ as a covariate were regressed against ‘end fitness’. However, considerable multicollinearity in the data (VIF >1000 for nine variables) meant that the multiple linear regression (MLR) process was unstable and so we developed a novel LOVO PLSCA adaptation to quantify the relative importance of the predictor variables and thus minimise multicollinearity issues. As such, the LOVO PLSCA was used as a tool to inform and refine the MLR process. Results: The LOVO PLSCA identified the distance accumulated at very-high speed (>7 m·s-1) as being the most important TL variable to influence improvement in player fitness, with this variable causing the largest decrease in singular value inertia (5.93). When included in a refined linear regression model, this variable, along with ‘starting fitness’ as a covariate, explained 73% of the variance in v30-15IFT ‘end fitness’ (p<0.001) and eliminated completely any multicollinearity issues. Conclusions: The LOVO PLSCA technique appears to be a useful tool for evaluating the relative importance of predictor variables in data sets that exhibit considerable multicollinearity. When used as a filtering tool, LOVO PLSCA produced a MLR model that demonstrated a significant relationship between ‘end fitness’ and the predictor variable ‘accumulated distance at very-high speed’ when ‘starting fitness’ was included as a covariate. As such, LOVO PLSCA may be a useful tool for sport scientists and coaches seeking to analyse data sets obtained using GPS and MEMS technologies. [ABSTRACT FROM AUTHOR]

This paper considers the DCSK system under jamming environment. We consider both fast and slow switching pulse jamming (PJ). We derive approximations of the system bit error rates (BERs) in analytic expressions containing only well-known special functions, from which we show that for both jamming cases increasing the spreading factor can enhance the BER. In addition, we reveal that under the fast switching PJ, the BER does not depend on the jamming duty cycle ρ when ρ ≤ 0.5, however when ρ > 0.5, increasing its value degrades the BER. Moreover, we find out that under the slow switching PJ, increasing ρ may either enhance or degrade the BER. [ABSTRACT FROM AUTHOR]

In this paper, a unique and more distinctive encryption algorithm is proposed. This is based on the complexity of highly nonlinear S box in Flesnelet domain. The nonlinear pattern is transformed further to enhance the confusion in the dummy data using Fresnelet technique. The security level of the encrypted image boosts using the algebra of Galois field in Fresnelet domain. At first level, the Fresnelet transform is used to propagate the given information with desired wavelength at specified distance. It decomposes given secret data into four complex subbands. These complex sub-bands are separated into two components of real subband data and imaginary subband data. At second level, the net subband data, produced at the first level, is deteriorated to non-linear diffused pattern using the unique S-box defined on the Galois field . In the diffusion process, the permuted image is substituted via dynamic algebraic S-box substitution. We prove through various analysis techniques that the proposed scheme enhances the cipher security level, extensively. [ABSTRACT FROM AUTHOR]

Managing the biodiversity extinction crisis requires wise decision-making processes able to account for the limited resources available. In most decision problems in conservation biology, several conflicting objectives have to be taken into account. Most methods used in conservation either provide suboptimal solutions or use strong assumptions about the decision-maker’s preferences. Our paper reviews some of the existing approaches to solve multi-objective decision problems and presents new multi-objective linear programming formulations of two multi-objective optimization problems in conservation, allowing the use of a reference point approach. Reference point approaches solve multi-objective optimization problems by interactively representing the preferences of the decision-maker with a point in the criteria (objectives) space, called the reference point. We modelled and solved the following two problems in conservation: a dynamic multi-species management problem under uncertainty and a spatial allocation resource management problem. Results show that the reference point method outperforms classic methods while illustrating the use of an interactive methodology for solving combinatorial problems with multiple objectives. The method is general and can be adapted to a wide range of ecological combinatorial problems. [ABSTRACT FROM AUTHOR]

The 3D orientation of clasts within a deposit are known to be informative on processes that formed that deposit. In archaeological sites, a portion of the clasts in the deposit are introduced by non-geological processes, and these are typically systematically recorded in archaeological excavations with total stations. By recording a second point on elongated clasts it is possible to quickly and precisely capture their orientation. The statistical and graphical techniques for analyzing these data are well published, and there is a growing set of actualistic and archaeological comparative data to help with the interpretation of the documented patterns. This paper advances this area of research in presenting methods to address some shortcomings in current methodologies. First, a method for calculating confidence intervals on orientation statistics is presented to help address the question of how many objects are needed to assess the formation of a deposit based on orientations. Second, a method for assessing the probability that two assemblages have different orientations is presented based on permutations testing. This method differs from existing ones in that it considers three-dimensional orientations rather than working separately with the two-dimensional bearing and plunge components. Third, a method is presented to examine spatial variability in orientations based on a moving windows approach. The raw data plus the R code to build this document and to implement these methods plus those already described by McPherron are included to help further their use in assessing archaeological site formation processes. [ABSTRACT FROM AUTHOR]

Background: DSC is used to determine thermally-induced conformational changes of biomolecules within a blood plasma sample. Recent research has indicated that DSC curves (or thermograms) may have different characteristics based on disease status and, thus, may be useful as a monitoring and diagnostic tool for some diseases. Since thermograms are curves measured over a range of temperature values, they are considered functional data. In this paper we apply functional data analysis techniques to analyze differential scanning calorimetry (DSC) data from individuals from the Lupus Family Registry and Repository (LFRR). The aim was to assess the effect of lupus disease status as well as additional covariates on the thermogram profiles, and use FD analysis methods to create models for classifying lupus vs. control patients on the basis of the thermogram curves. Methods: Thermograms were collected for 300 lupus patients and 300 controls without lupus who were matched with diseased individuals based on sex, race, and age. First, functional regression with a functional response (DSC) and categorical predictor (disease status) was used to determine how thermogram curve structure varied according to disease status and other covariates including sex, race, and year of birth. Next, functional logistic regression with disease status as the response and functional principal component analysis (FPCA) scores as the predictors was used to model the effect of thermogram structure on disease status prediction. The prediction accuracy for patients with Osteoarthritis and Rheumatoid Arthritis but without Lupus was also calculated to determine the ability of the classifier to differentiate between Lupus and other diseases. Data were divided 1000 times into separate 2/3 training and 1/3 test data for evaluation of predictions. Finally, derivatives of thermogram curves were included in the models to determine whether they aided in prediction of disease status. Results: Functional regression with thermogram as a functional response and disease status as predictor showed a clear separation in thermogram curve structure between cases and controls. The logistic regression model with FPCA scores as the predictors gave the most accurate results with a mean 79.22% correct classification rate with a mean sensitivity = 79.70%, and specificity = 81.48%. The model correctly classified OA and RA patients without Lupus as controls at a rate of 75.92% on average with a mean sensitivity = 79.70% and specificity = 77.6%. Regression models including FPCA scores for derivative curves did not perform as well, nor did regression models including covariates. Conclusion: Changes in thermograms observed in the disease state likely reflect covalent modifications of plasma proteins or changes in large protein-protein interacting networks resulting in the stabilization of plasma proteins towards thermal denaturation. By relating functional principal components from thermograms to disease status, our Functional Principal Component Analysis model provides results that are more easily interpretable compared to prior studies. Further, the model could also potentially be coupled with other biomarkers to improve diagnostic classification for lupus. [ABSTRACT FROM AUTHOR]

Code-based cryptography is one of few alternatives supposed to be secure in a post-quantum world. Meanwhile, identity-based identification and signature (IBI/IBS) schemes are two of the most fundamental cryptographic primitives, so several code-based IBI/IBS schemes have been proposed. However, with increasingly profound researches on coding theory, the security reduction and efficiency of such schemes have been invalidated and challenged. In this paper, we construct provably secure IBI/IBS schemes from code assumptions against impersonation under active and concurrent attacks through a provably secure code-based signature technique proposed by Preetha, Vasant and Rangan (PVR signature), and a security enhancement Or-proof technique. We also present the parallel-PVR technique to decrease parameter values while maintaining the standard security level. Compared to other code-based IBI/IBS schemes, our schemes achieve not only preferable public parameter size, private key size, communication cost and signature length due to better parameter choices, but also provably secure. [ABSTRACT FROM AUTHOR]

Muirhead mean (MM) is a well-known aggregation operator which can consider interrelationships among any number of arguments assigned by a variable vector. Besides, it is a universal operator since it can contain other general operators by assigning some special parameter values. However, the MM can only process the crisp numbers. Inspired by the MM’ advantages, the aim of this paper is to extend MM to process the intuitionistic fuzzy numbers (IFNs) and then to solve the multi-attribute group decision making (MAGDM) problems. Firstly, we develop some intuitionistic fuzzy Muirhead mean (IFMM) operators by extending MM to intuitionistic fuzzy information. Then, we prove some properties and discuss some special cases with respect to the parameter vector. Moreover, we present two new methods to deal with MAGDM problems with the intuitionistic fuzzy information based on the proposed MM operators. Finally, we verify the validity and reliability of our methods by using an application example, and analyze the advantages of our methods by comparing with other existing methods. [ABSTRACT FROM AUTHOR]

In a general (k, n) scalable secret image sharing (SSIS) scheme, the secret image is shared by n participants and any k or more than k participants have the ability to reconstruct it. The scalability means that the amount of information in the reconstructed image scales in proportion to the number of the participants. In most existing SSIS schemes, the size of each image shadow is relatively large and the dealer does not has a flexible control strategy to adjust it to meet the demand of differen applications. Besides, almost all existing SSIS schemes are not applicable under noise circumstances. To address these deficiencies, in this paper we present a novel SSIS scheme based on a brand-new technique, called compressed sensing, which has been widely used in many fields such as image processing, wireless communication and medical imaging. Our scheme has the property of flexibility, which means that the dealer can achieve a compromise between the size of each shadow and the quality of the reconstructed image. In addition, our scheme has many other advantages, including smooth scalability, noise-resilient capability, and high security. The experimental results and the comparison with similar works demonstrate the feasibility and superiority of our scheme. [ABSTRACT FROM AUTHOR]

In this paper we present a three-dimensional (3D) morphometrical assessment of human tibia sexual dimorphism based on whole bone digital representation. To detect shape–size and shape differences between sexes, we used geometric morphometric tools and colour-coded surface deviation maps. The surface-based methodology enabled analysis of sexually dimorphic features throughout the shaft and articular ends of the tibia. The overall study dataset consisted of 183 3D models of adult tibiae from three Czech population subsets, dating to the early medieval (9–10th century) (N = 65), early 20th century (N = 61) and 21st-century (N = 57). The time gap between the chronologically most distant and contemporary datasets was more than 1200 years. The results showed that, in all three datasets, sexual dimorphism was pronounced. There were some sex-dimorphic characteristics common to all three samples, such as tuberosity protrusion, anteriorly bowed shaft and relatively larger articular ends in males. Diachronic comparisons also revealed substantial shape variation related to the most dimorphic area. Male/female distinctions showed a consistent temporal trend regarding the location of dimorphic areas (shifting distally with time), while the maximal deviation between male and female digitized surfaces fluctuated and reached the lowest level in the 21st-century sample. Sex determination on a whole-surface basis yielded the lowest return of correct sex assignment in the 20th-century group, which represented the lowest socioeconomic status. The temporal variation could be attributed to changes in living conditions, the decreasing lower limb loading/labour division in the last 12 centuries having the greatest effect. Overall, the results showed that a surface-based approach is successful for analysing complex long bone geometry. [ABSTRACT FROM AUTHOR]

Data analysis and model-data comparisons in the environmental sciences require diagnostic measures that quantify time series dynamics and structure, and are robust to noise in observational data. This paper investigates the temporal dynamics of environmental time series using measures quantifying their information content and complexity. The measures are used to classify natural processes on one hand, and to compare models with observations on the other. The present analysis focuses on the global carbon cycle as an area of research in which model-data integration and comparisons are key to improving our understanding of natural phenomena. We investigate the dynamics of observed and simulated time series of Gross Primary Productivity (GPP), a key variable in terrestrial ecosystems that quantifies ecosystem carbon uptake. However, the dynamics, patterns and magnitudes of GPP time series, both observed and simulated, vary substantially on different temporal and spatial scales. We demonstrate here that information content and complexity, or Information Theory Quantifiers (ITQ) for short, serve as robust and efficient data-analytical and model benchmarking tools for evaluating the temporal structure and dynamical properties of simulated or observed time series at various spatial scales. At continental scale, we compare GPP time series simulated with two models and an observations-based product. This analysis reveals qualitative differences between model evaluation based on ITQ compared to traditional model performance metrics, indicating that good model performance in terms of absolute or relative error does not imply that the dynamics of the observations is captured well. Furthermore, we show, using an ensemble of site-scale measurements obtained from the FLUXNET archive in the Mediterranean, that model-data or model-model mismatches as indicated by ITQ can be attributed to and interpreted as differences in the temporal structure of the respective ecological time series. At global scale, our understanding of C fluxes relies on the use of consistently applied land models. Here, we use ITQ to evaluate model structure: The measures are largely insensitive to climatic scenarios, land use and atmospheric gas concentrations used to drive them, but clearly separate the structure of 13 different land models taken from the CMIP5 archive and an observations-based product. In conclusion, diagnostic measures of this kind provide data-analytical tools that distinguish different types of natural processes based solely on their dynamics, and are thus highly suitable for environmental science applications such as model structural diagnostics. [ABSTRACT FROM AUTHOR]

Identifying causal relations from time series is the first step to understanding the behavior of complex systems. Although many methods have been proposed, few papers have applied multiple methods together to detect causal relations based on time series generated from coupled nonlinear systems with some unobserved parts. Here we propose the combined use of three methods and a majority vote to infer causality under such circumstances. Two of these methods are proposed here for the first time, and all of the three methods can be applied even if the underlying dynamics is nonlinear and there are hidden common causes. We test our methods with coupled logistic maps, coupled Rössler models, and coupled Lorenz models. In addition, we show from ice core data how the causal relations among the temperature, the CH4 level, and the CO2 level in the atmosphere changed in the last 800,000 years, a conclusion also supported by irregularly sampled data analysis. Moreover, these methods show how three regions of the brain interact with each other during the visually cued, two-choice arm reaching task. Especially, we demonstrate that this is due to bottom up influences at the beginning of the task, while there exist mutual influences between the posterior medial prefrontal cortex and the presupplementary motor area. Based on our results, we conclude that identifying causality with an appropriate ensemble of multiple methods ensures the validity of the obtained results more firmly. [ABSTRACT FROM AUTHOR]

The joint analysis of multiple traits has recently become popular since it can increase statistical power to detect genetic variants and there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Currently, most of existing methods use all of the traits for testing the association between multiple traits and a single variant. However, those methods for association studies may lose power in the presence of a large number of noise traits. In this paper, we propose an “optimal” maximum heritability test (MHT-O) to test the association between multiple traits and a single variant. MHT-O includes a procedure of deleting traits that have weak or no association with the variant. Using extensive simulation studies, we compare the performance of MHT-O with MHT, Trait-based Association Test uses Extended Simes procedure (TATES), SUM_SCORE and MANOVA. Our results show that, in all of the simulation scenarios, MHT-O is either the most powerful test or comparable to the most powerful test among the five tests we compared. [ABSTRACT FROM AUTHOR]

Graphlets are small subgraphs, usually containing up to five vertices, that can be found in a larger graph. Identification of the graphlets that a vertex in an explored graph touches can provide useful information about the local structure of the graph around that vertex. Actually finding all graphlets in a large graph can be time-consuming, however. As the graphlets grow in size, more different graphlets emerge and the time needed to find each graphlet also scales up. If it is not needed to find each instance of each graphlet, but knowing the number of graphlets touching each node of the graph suffices, the problem is less hard. Previous research shows a way to simplify counting the graphlets: instead of looking for the graphlets needed, smaller graphlets are searched, as well as the number of common neighbors of vertices. Solving a system of equations then gives the number of times a vertex is part of each graphlet of the desired size. However, until now, equations only exist to count graphlets with 4 or 5 nodes. In this paper, two new techniques are presented. The first allows to generate the equations needed in an automatic way. This eliminates the tedious work needed to do so manually each time an extra node is added to the graphlets. The technique is independent on the number of nodes in the graphlets and can thus be used to count larger graphlets than previously possible. The second technique gives all graphlets a unique ordering which is easily extended to name graphlets of any size. Both techniques were used to generate equations to count graphlets with 4, 5 and 6 vertices, which extends all previous results. Code can be found at and . [ABSTRACT FROM AUTHOR]

The evolutionary history of certain species such as polyploids are modeled by a generalization of phylogenetic trees called multi-labeled phylogenetic trees, or MUL trees for short. One problem that relates to inferring a MUL tree is how to construct the smallest possible MUL tree that is consistent with a given set of rooted triplets, or SMRT problem for short. This problem is NP-hard. There is one algorithm for the SMRT problem which is exact and runs in time, where is the number of taxa. In this paper, we show that the SMRT does not seem to be an appropriate solution from the biological point of view. Indeed, we present a heuristic algorithm named MTRT for this problem and execute it on some real and simulated datasets. The results of MTRT show that triplets alone cannot provide enough information to infer the true MUL tree. So, it is inappropriate to infer a MUL tree using triplet information alone and considering the minimum number of duplications. Finally, we introduce some new problems which are more suitable from the biological point of view. [ABSTRACT FROM AUTHOR]

The reconcilability of actions and beliefs in inter-country relationships, either in business or politics, is of vital importance as incorrect beliefs on foreigners’ behavior can have serious implications. We study a typical inter-country interaction by means of a controlled laboratory investment game experiment in Germany, Israel and Palestine involving 400 student participants in total. An investor has to take a risky decision in a foreign country that involves transferring money to an investee/allocator. We found a notable constellation of calibrated and un-calibrated beliefs. Within each country, transfer standards exist, which investees correctly anticipate within their country. However, across countries these standards differ. By attributing the standard of their own environment to the other countries investees are remarkably bad in predicting foreign investors’ behavior. The tendency to ignore this potential difference can be a source of misinterpreting motives in cross-country interaction. Foreigners might perceive behavior as unfavorable or favorable differentiation, even though—unknown to them—investors actually treat fellow-country people and foreigners alike. [ABSTRACT FROM AUTHOR]

The bioaccumulation of Potentially Toxic Elements (PTEs) by benthic invertebrates in estuarine sediments is poorly understood. We sampled and analysed PTEs in sediments and benthic invertebrates from five sites in the Skeena Estuary (British Columbia, Canada), including sites adjacent to an abandoned cannery and a decommissioned papermill. Our aim was to elucidate baseline levels of PTE concentrations at sites that may be recovering from disturbance associated with prior industrial development and identify organisms that could be used to biomonitor the impact of future industrial developments. There was no indication that sediments of the salmon cannery were polluted, but acidic sediments adjacent to the papermill contained elevated concentrations of Cd, Cr, Hg and Pb. Benthic invertebrate community assemblages confirm that sediments have mostly recovered from prior industrial development associated with discharge of papermill sludge. Overall, we did not observe any relationship between PTE concentrations in the sediment and PTE concentrations in invertebrate tissues. However, we did observe a negative relationship between sediment pH and the Biota-Sediment Accumulation Factor (BSAF) of most PTEs for Oregon pill bugs (Gnorimosphaeroma oregonensis). G. oregonensis, observed at all sites, feeds on the fibers associated with the papermill discharge. Thus, G. oregonensis is a useful biomonitors for quantifying the impact of the decommissioned papermill, and are candidate biomonitors for assessing the impact of similar industrial development projects on intertidal ecosystems. [ABSTRACT FROM AUTHOR]

Downscaled climate projections need to be linked to downscaled projections of population and economic growth to fully develop implications for land, natural resources, and ecosystems for future scenarios. We develop an empirical spatiotemporal approach for jointly projecting population and income at the county scale in the United States that is consistent with neoclassical economic growth theory and overlapping labor markets and that accounts for labor migration and spatial spillovers. Downscaled projections generated for the five Shared Socioeconomic Pathways used to support global scenario analysis generally show growth focused around relatively few centers especially in the southeast and western regions, with some areas in the Midwest and northeast experiencing population declines. Results are consistent with economic growth theory and with historical trends in population change and convergence of per capita personal income across US counties. [ABSTRACT FROM AUTHOR]

In primates, both the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (dlPFC) are key regions of the frontoparietal cognitive control network. To study the role of the dACC and its communication with the dlPFC in cognitive control, we recorded local field potentials (LFPs) from the dlPFC before and during the reversible deactivation of the dACC, in macaque monkeys engaging in uncued switches between 2 stimulus-response rules, namely prosaccade and antisaccade. Cryogenic dACC deactivation impaired response accuracy during maintenance of—but not the initial switching to—the cognitively demanding antisaccade rule, which coincided with a reduction in task-related theta activity and the correct-error (C-E) difference in dlPFC beta-band power. During both rule switching and maintenance, dACC deactivation prolonged the animals’ reaction time and reduced task-related alpha power in the dlPFC. Our findings support a role of the dACC in prefrontal oscillatory activities that are involved the maintenance of a new, challenging task rule. [ABSTRACT FROM AUTHOR]

The Complexity-entropy causality plane (CECP) is a parsimonious representation space for time series. It has only two dimensions: normalized permutation entropy () and Jensen-Shannon complexity () of a time series. This two-dimensional representation allows for detection of slow or rapid drifts in the condition of mechanical components monitored through sensor measurements. The CECP representation can be used for both predictive analytics and visual monitoring of changes in component condition. This method requires minimal pre-processing of raw signals. Furthermore, it is insensitive to noise, stationarity, and trends. These desirable properties make CECP a good candidate for machine condition monitoring and fault diagnostics. In this work we study the effectiveness of CECP on three rotary component condition assessment applications. We use CECP representation of vibration signals to differentiate various machine component health conditions for rotary machine components, namely roller bearing and gears. The results confirm that the CECP representation is able to detect, with high accuracy, changes in underlying dynamics of machine component degradation states. From class separability perspective, the CECP representation is able to generate linearly separable classes for the classification of different fault states. This classification performance improves with increasing signal length. For signal length of 16,384 data points, the fault classification accuracy varies from 90% to 100% for bearing applications, and from 85% to 100% for gear applications. We observed that the optimum parameter for CECP representatino depends on the application. For bearing applications we found that embedding dimension D = 4, 5, 6, and embedding delay τ = 1, 2, 3 are suitable for good fault classification. For gear applications we find that embedding dimension D = 4, 5, and embedding delay τ = 1, 5 are suitable for fault classification. [ABSTRACT FROM AUTHOR]

Despite intensive study, most of the specific genetic factors that contribute to variation in human height remain undiscovered. We conducted a family-based linkage study of height in a unique cohort of very large nuclear families from a founder (Jewish) population. This design allowed for increased power to detect linkage, compared to previous family-based studies. Loci we identified in discovery families could explain an estimated lower bound of 6% of the variance in height in validation families. We showed that these loci are not tagging known common variants associated with height. Rather, we suggest that the observed signals arise from variants with large effects that are rare globally but elevated in frequency in the Jewish population. [ABSTRACT FROM AUTHOR]

Humans and other animals are able to discover underlying statistical structure in their environments and exploit it to achieve efficient and effective performance. However, such structure is often difficult to learn and use because it is obscure, involving long-range temporal dependencies. Here, we analysed behavioural data from an extended experiment with rats, showing that the subjects learned the underlying statistical structure, albeit suffering at times from immediate inferential imperfections as to their current state within it. We accounted for their behaviour using a Hidden Markov Model, in which recent observations are integrated with evidence from the past. We found that over the course of training, subjects came to track their progress through the task more accurately, a change that our model largely attributed to improved integration of past evidence. This learning reflected the structure of the task, decreasing reliance on recent observations, which were potentially misleading. [ABSTRACT FROM AUTHOR]

While prediction errors (PE) have been established to drive learning through adaptation of internal models, the role of model-compliant events in predictive processing is less clear. Checkpoints (CP) were recently introduced as points in time where expected sensory input resolved ambiguity regarding the validity of the internal model. Conceivably, these events serve as on-line reference points for model evaluation, particularly in uncertain contexts. Evidence from fMRI has shown functional similarities of CP and PE to be independent of event-related surprise, raising the important question of how these event classes relate to one another. Consequently, the aim of the present study was to characterise the functional relationship of checkpoints and prediction errors in a serial pattern detection task using electroencephalography (EEG). Specifically, we first hypothesised a joint P3b component of both event classes to index recourse to the internal model (compared to non-informative standards, STD). Second, we assumed the mismatch signal of PE to be reflected in an N400 component when compared to CP. Event-related findings supported these hypotheses. We suggest that while model adaptation is instigated by prediction errors, checkpoints are similarly used for model evaluation. Intriguingly, behavioural subgroup analyses showed that the exploitation of potentially informative reference points may depend on initial cue learning: Strict reliance on cue-based predictions may result in less attentive processing of these reference points, thus impeding upregulation of response gain that would prompt flexible model adaptation. Overall, present results highlight the role of checkpoints as model-compliant, informative reference points and stimulate important research questions about their processing as function of learning und uncertainty. [ABSTRACT FROM AUTHOR]

Several recent studies have shown that neural activity in vivo tends to be constrained to a low-dimensional manifold. Such activity does not arise in simulated neural networks with homogeneous connectivity and it has been suggested that it is indicative of some other connectivity pattern in neuronal networks. In particular, this connectivity pattern appears to be constraining learning so that only neural activity patterns falling within the intrinsic manifold can be learned and elicited. Here, we use three different models of spiking neural networks (FORCE learning, the Neural Engineering Framework and Efficient Coding) to demonstrate how the intrinsic manifold can be made a direct consequence of the circuit connectivity. Using this relationship between the circuit connectivity and the intrinsic manifold, we show that learning patterns outside the intrinsic manifold corresponds to much larger changes in synaptic weights than learning patterns within the intrinsic manifold. Assuming larger changes to synaptic weights requires extensive learning, this observation provides an explanation of why learning is easier when it does not require the neural activity to leave its intrinsic manifold. [ABSTRACT FROM AUTHOR]

Recent large cancer studies have measured somatic alterations in an unprecedented number of tumours. These large datasets allow the identification of cancer-related sets of genetic alterations by identifying relevant combinatorial patterns. Among such patterns, mutual exclusivity has been employed by several recent methods that have shown its effectiveness in characterizing gene sets associated to cancer. Mutual exclusivity arises because of the complementarity, at the functional level, of alterations in genes which are part of a group (e.g., a pathway) performing a given function. The availability of quantitative target profiles, from genetic perturbations or from clinical phenotypes, provides additional information that can be leveraged to improve the identification of cancer related gene sets by discovering groups with complementary functional associations with such targets. In this work we study the problem of finding groups of mutually exclusive alterations associated with a quantitative (functional) target. We propose a combinatorial formulation for the problem, and prove that the associated computational problem is computationally hard. We design two algorithms to solve the problem and implement them in our tool UNCOVER. We provide analytic evidence of the effectiveness of UNCOVER in finding high-quality solutions and show experimentally that UNCOVER finds sets of alterations significantly associated with functional targets in a variety of scenarios. In particular, we show that our algorithms find sets which are better than the ones obtained by the state-of-the-art method, even when sets are evaluated using the statistical score employed by the latter. In addition, our algorithms are much faster than the state-of-the-art, allowing the analysis of large datasets of thousands of target profiles from cancer cell lines. We show that on two such datasets, one from project Achilles and one from the Genomics of Drug Sensitivity in Cancer project, UNCOVER identifies several significant gene sets with complementary functional associations with targets. Software available at: . [ABSTRACT FROM AUTHOR]

In this note we present a robust bootstrap test with good Type I error control for testing the general hypothesis H0: ρ = ρ0. In order to carry out this test we use what is termed a surrogate bootstrap distribution. The test was inspired by the studentized permutation for testing H0: ρ = 0, which was proven to be exact in certain scenarios and asymptotically correct overall. We show that the bootstrap based test is robust to a variety of distributional scenarios in terms of proper Type I error control. [ABSTRACT FROM AUTHOR]

Triatomine vectors transmit Trypanosoma cruzi, the etiological agent of Chagas disease in humans. Transmission to humans typically occurs when contaminated triatomine feces come in contact with the bite site or mucosal membranes. In the Southern Cone of South America, where the highest burden of disease exists, Triatoma infestans is the principal vector for T. cruzi. Recent studies of other vector-borne illnesses have shown that arthropod microbiota influences the ability of infectious agents to colonize the insect vector and transmit to the human host. This has garnered attention as a potential control strategy against T. cruzi, as vector control is the main tool of Chagas disease prevention. Here we characterized the microbiota in T. infestans feces of both wild-caught and laboratory-reared insects and examined the relationship between microbial composition and T. cruzi infection using highly sensitive high-throughput sequencing technology to sequence the V3-V4 region of the 16S ribosomal RNA gene on the MiSeq Illumina platform. We collected 59 wild (9 with T. cruzi infection) and 10 lab-reared T. infestans (4 with T. cruzi infection) from the endemic area of Arequipa, Perú. Wild T. infestans had greater hindgut bacterial diversity than laboratory-reared bugs. Microbiota of lab insects comprised a subset of those identified in their wild counterparts, with 96 of the total 124 genera also observed in laboratory-reared insects. Among wild insects, variation in bacterial composition was observed, but time and location of collection and development stage did not explain this variation. T. cruzi infection in lab insects did not affect α- or β-diversity; however, we did find that the β-diversity of wild insects differed if they were infected with T. cruzi and identified 10 specific taxa that had significantly different relative abundances in infected vs. uninfected wild T. infestans (Bosea, Mesorhizobium, Dietzia, and Cupriavidus were underrepresented in infected bugs; Sporosarcina, an unclassified genus of Porphyromonadaceae, Nestenrenkonia, Alkalibacterium, Peptoniphilus, Marinilactibacillus were overrepresented in infected bugs). Our findings suggest that T. cruzi infection is associated with the microbiota of T. infestans and that inferring the microbiota of wild T. infestans may not be possible through sampling of T. infestans reared in the insectary. [ABSTRACT FROM AUTHOR]

Despite ongoing large-scale population-based whole-genome sequencing (WGS) projects such as the NIH NHLBI TOPMed program and the NHGRI Genome Sequencing Program, WGS-based association analysis of complex traits remains a tremendous challenge due to the large number of rare variants, many of which are non-trait-associated neutral variants. External biological knowledge, such as functional annotations based on the ENCODE, Epigenomics Roadmap and GTEx projects, may be helpful in distinguishing causal rare variants from neutral ones; however, each functional annotation can only provide certain aspects of the biological functions. Our knowledge for selecting informative annotations a priori is limited, and incorporating non-informative annotations will introduce noise and lose power. We propose FunSPU, a versatile and adaptive test that incorporates multiple biological annotations and is adaptive at both the annotation and variant levels and thus maintains high power even in the presence of noninformative annotations. In addition to extensive simulations, we illustrate our proposed test using the TWINSUK cohort (n = 1,752) of UK10K WGS data based on six functional annotations: CADD, RegulomeDB, FunSeq, Funseq2, GERP++, and GenoSkyline. We identified genome-wide significant genetic loci on chromosome 19 near gene TOMM40 and APOC4-APOC2 associated with low-density lipoprotein (LDL), which are replicated in the UK10K ALSPAC cohort (n = 1,497). These replicated LDL-associated loci were missed by existing rare variant association tests that either ignore external biological information or rely on a single source of biological knowledge. We have implemented the proposed test in an R package “FunSPU”. [ABSTRACT FROM AUTHOR]

China's rapid urbanization and high traffic accident frequency have received many researchers’ attention. It is important to reveal how urban infrastructures and other risk factors affects the traffic accident frequency. A growing amount of research has examined the local risk factors impact on traffic accident frequency at certain time. Some studies considered these spatial influences but overlooked the temporal correlation/heterogeneity of traffic accidents and related risk factors. This study explores risk factors’ influence on urban traffic accidents frequency while considering both the spatial and temporal correlation/heterogeneity of traffic accidents. The study area is split into 100 equally sized rectangle traffic analysis zones (TAZs), and the urban traffic accident frequency and attributes in each TAZ are extracted. The linear regression model, spatial lag model (SLM), spatial error model (SEM) and time-fixed effects error model (T-FEEM) are established and compared respectively. The proposed methodologies are illustrated using ten-month traffic accident data from the urban area of Guiyang City, China. The results reveal that the time-fixed effects error model, which considers both spatial and temporal correlation/heterogeneity of traffic accidents, is superior to other models. More traffic accidents will happen in those TAZs that have more hospitals or schools. Moreover, hospitals have a greater influence on traffic accidents than schools. Because of the location in the margin of the city, those TAZs that have passenger stations have more traffic accidents. This study provides policy makers with more detailed characterization about the impact of related risk factors on traffic accident frequencies, and it is suggested that not only the spatial correlation/heterogeneity but also the temporal correlation/heterogeneity should be taken into account in guiding traffic accident control of urban area. [ABSTRACT FROM AUTHOR]

Synchronized oscillatory gamma-band activity (30-100Hz) has been suggested to constitute a key mechanism to dynamically orchestrate sensory information integration across multiple spatio-temporal scales. We here tested whether interhemispheric functional connectivity and ensuing auditory perception can selectively be modulated by high-density transcranial alternating current stimulation (HD-tACS). For this purpose, we applied multi-site HD-tACS at 40Hz bilaterally with a phase lag of 180° and recorded a 64-channel EEG to study the oscillatory phase dynamics at the source-space level during a dichotic listening (DL) task in twenty-six healthy participants. In this study, we revealed an oscillatory phase signature at 40Hz which reflects different temporal profiles of the phase asymmetries during left and right ear percept. Here we report that 180°-tACS did not affect the right ear advantage during DL at group level. However, a follow-up analysis revealed that the intrinsic phase asymmetries during sham-tACS determined the directionality of the behavioral modulations: While a shift to left ear percept was associated with augmented interhemispheric asymmetry (closer to 180°), a shift to right ear processing was elicited in subjects with lower asymmetry (closer to 0°). Crucially, the modulation of the interhemispheric network dynamics depended on the deviation of the tACS-induced phase-lag from the intrinsic phase asymmetry. Our characterization of the oscillatory network trends is giving rise to the importance of phase-specific gamma-band coupling during ambiguous auditory perception, and emphasizes the necessity to address the inter-individual variability of phase asymmetries in future studies by tailored stimulation protocols. [ABSTRACT FROM AUTHOR]

Small sample sizes combined with high person-to-person variability can make it difficult to detect significant gene expression changes from transcriptional profiling studies. Subtle, but coordinated, gene expression changes may be detected using gene set analysis approaches. Meta-analysis is another approach to increase the power to detect biologically relevant changes by integrating information from multiple studies. Here, we present a framework that combines both approaches and allows for meta-analysis of gene sets. QuSAGE meta-analysis extends our previously published QuSAGE framework, which offers several advantages for gene set analysis, including fully accounting for gene-gene correlations and quantifying gene set activity as a full probability density function. Application of QuSAGE meta-analysis to influenza vaccination response shows it can detect significant activity that is not apparent in individual studies. [ABSTRACT FROM AUTHOR]

Commercial surrogacy in emerging countries such as India is often associated with exploitation of vulnerable women, the assumption being that it is performed by poor and uneducated women for rich intended parents. However, the hypothesis that surrogates are poor women has rarely been confronted with field data. The objective was to compare the socioeconomic characteristics of Indian surrogates interviewed in social studies with those of Indian women in the general population in order to provide preliminary data on whether surrogates have a specific profile and are indeed disadvantaged compared with their counterparts. The study analyzes the data from four cross-sectional studies carried out in India among surrogates between 2006 and 2014. Surrogates were recruited through clinics, agencies and agents. Data were collected during face-to-face interviews. The resulting convenience sample included 96 Indian surrogates. Their sociodemographic characteristics were compared with those of the general population extracted from Indian national surveys. The surrogates interviewed had their first child at a younger age than women in the general population, but they tended to have a smaller family. Their social situation tended to be better than that of the general population in terms of education, employment and family income. These results provide first empirical evidence moderating the common assumption that Indian surrogates are the poorest and least educated women. This does not mean, however, that exploitation does not exist. More studies are needed to confirm these results and to explore the issue in new international destinations for surrogacy. [ABSTRACT FROM AUTHOR]

We present CoPhosK to predict kinase-substrate associations for phosphopeptide substrates detected by mass spectrometry (MS). The tool utilizes a Naïve Bayes framework with priors of known kinase-substrate associations (KSAs) to generate its predictions. Through the mining of MS data for the collective dynamic signatures of the kinases’ substrates revealed by correlation analysis of phosphopeptide intensity data, the tool infers KSAs in the data for the considerable body of substrates lacking such annotations. We benchmarked the tool against existing approaches for predicting KSAs that rely on static information (e.g. sequences, structures and interactions) using publically available MS data, including breast, colon, and ovarian cancer models. The benchmarking reveals that co-phosphorylation analysis can significantly improve prediction performance when static information is available (about 35% of sites) while providing reliable predictions for the remainder, thus tripling the KSAs available from the experimental MS data providing to a comprehensive and reliable characterization of the landscape of kinase-substrate interactions well beyond current limitations. [ABSTRACT FROM AUTHOR]

New approaches to lineage tracking have allowed the study of differentiation in multicellular organisms over many generations of cells. Understanding the phenotypic variability observed in these lineage trees requires new statistical methods. Whereas an invariant cell lineage, such as that for the nematode Caenorhabditis elegans, can be described by a lineage map, defined as the pattern of phenotypes overlaid onto the binary tree, a traditional lineage map is static and does not describe the variability inherent in the cell lineages of higher organisms. Here, we introduce lineage variability maps which describe the pattern of second-order variation in lineage trees. These maps can be undirected graphs of the partial correlations between every lineal position, or directed graphs showing the dynamics of bifurcated patterns in each subtree. We show how to infer these graphical models for lineages of any depth from sample sizes of only a few pedigrees. This required developing the generalized spectral analysis for a binary tree, the natural framework for describing tree-structured variation. When tested on pedigrees from C. elegans expressing a marker for pharyngeal differentiation potential, the variability maps recover essential features of the known lineage map. When applied to highly-variable pedigrees monitoring cell size in T lymphocytes, the maps show that most of the phenotype is set by the founder naive T cell. Lineage variability maps thus elevate the concept of the lineage map to the population level, addressing questions about the potency and dynamics of cell lineages and providing a way to quantify the progressive restriction of cell fate with increasing depth in the tree. [ABSTRACT FROM AUTHOR]

We propose a set of family-based burden and kernel tests for censored traits (FamBAC and FamKAC). Here, censored traits refer to time-to-event outcomes, for instance, age-at-onset of a disease. To model censored traits in family-based designs, we used the frailty model, which incorporated not only fixed genetic effects of rare variants in a region of interest but also random polygenic effects shared within families. We first partitioned genotype scores of rare variants into orthogonal between- and within-family components, and then derived their corresponding efficient score statistics from the frailty model. Finally, FamBAC and FamKAC were constructed by aggregating the weighted efficient scores of the within-family components across rare variants and subjects. FamBAC collapsed rare variants within subject first to form a burden test that followed a chi-squared distribution; whereas FamKAC was a variant component test following a mixture of chi-squared distributions. For FamKAC, p-values can be computed by permutation tests or for computational efficiency by approximation methods. Through simulation studies, we showed that type I error was correctly controlled by FamBAC for various variant weighting schemes (0.0371 to 0.0527). However, FamKAC type I error rates based on approximation methods were deflated (max 0.0376) but improved by permutation tests. Our simulations also demonstrated that burden test FamBAC had higher power than kernel test FamKAC when high proportion (e.g. ≥ 80%) of causal variants had effects in the same direction. In contrast, when the effects of causal variants on the censored trait were in mixed directions, FamKAC outperformed FamBAC and had comparable or higher power than an existing method, RVFam. Our proposed framework has the flexibility to accommodate general nuclear families, and can be used to analyze sequence data for censored traits such as age-at-onset of a complex disease of interest. [ABSTRACT FROM AUTHOR]

Metabolomics is a powerful approach for discovering biomarkers and for characterizing the biochemical consequences of genetic variation. While untargeted metabolite profiling can measure thousands of signals in a single experiment, many biologically meaningful signals cannot be readily identified as known metabolites nor compared across datasets, making it difficult to infer biology and to conduct well-powered meta-analyses across studies. To overcome these challenges, we developed a suite of computational methods, PAIRUP-MS, to match metabolite signals across mass spectrometry-based profiling datasets and to generate metabolic pathway annotations for these signals. To pair up signals measured in different datasets, where retention times (RT) are often not comparable or even available, we implemented an imputation-based approach that only requires mass-to-charge ratios (m/z). As validation, we treated each shared known metabolite as an unmatched signal and showed that PAIRUP-MS correctly matched 70–88% of these metabolites from among thousands of signals, equaling or outperforming a standard m/z- and RT-based approach. We performed further validation using genetic data: the most stringent set of matched signals and shared knowns showed comparable consistency of genetic associations across datasets. Next, we developed a pathway reconstitution method to annotate unknown signals using curated metabolic pathways containing known metabolites. We performed genetic validation for the generated annotations, showing that annotated signals associated with gene variants were more likely to be enriched for pathways functionally related to the genes compared to random expectation. Finally, we applied PAIRUP-MS to study associations between metabolites and genetic variants or body mass index (BMI) across multiple datasets, identifying up to ~6 times more significant signals and many more BMI-associated pathways compared to the standard practice of only analyzing known metabolites. These results demonstrate that PAIRUP-MS enables analysis of unknown signals in a robust, biologically meaningful manner and provides a path to more comprehensive, well-powered studies of untargeted metabolomics data. [ABSTRACT FROM AUTHOR]

We used an ensemble of statistical methods to build a model that predicts kidney transplant survival and identifies important predictive variables. The proposed model achieved better performance, measured by Harrell’s concordance index, than the Estimated Post Transplant Survival model used in the kidney allocation system in the U.S., and other models published recently in the literature. The model has a five-year concordance index of 0.724 (in comparison, the concordance index is 0.697 for the Estimated Post Transplant Survival model, the state of the art currently in use). It combines predictions from random survival forests with a Cox proportional hazards model. The rankings of importance for the model’s variables differ by transplant recipient age. Better survival predictions could eventually lead to more efficient allocation of kidneys and improve patient outcomes. [ABSTRACT FROM AUTHOR]