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Many complex physical systems exhibit a rich variety of discrete behavioural modes. Often, the system complexity limits the applicability of standard modelling tools. Hence, understanding the underlying physics of different behaviours and distinguishing between them is challenging. Although traditional machine learning techniques could predict and classify behaviour well, typically they do not provide any meaningful insight into the underlying physics of the system. In this paper we present a novel method for extracting physically meaningful clusters of discrete behaviour from limited experimental observations. This method obtains a set of physically plausible functions that both facilitate behavioural clustering and aid in system understanding. We demonstrate the approach on the V-shaped falling paper system, a new falling paper type system that exhibits four distinct behavioural modes depending on a few morphological parameters. Using just 49 experimental observations, the method discovered a set of candidate functions that distinguish behaviours with an error of 2.04%, while also aiding insight into the physical phenomena driving each behaviour. © 2019 Howison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

We give an overview of our critiques of "proofs" of security and a guide to our papers on the subject that have appeared over the past decade and a half. We also provide numerous additional examples and a few updates and errata.

This discussion provides our reaction to the article by Greven and Scheipl. It contains an overview of their article and a description of the many areas of research that remain open and could benefit from further methodological and computational development.

The mission of theoretical cryptography is to define and construct provably secure cryptographic protocols and schemes. Without proofs of security, cryptographic constructs offer no guarantees whatsoever and no basis for evaluation and comparison. As most security proofs necessarily come in the form of a reduction between the security claim and an intractability assumption, such proofs are ultimately only as good as the assumptions they are based on. Thus, the complexity implications of every assumption we utilize should be of significant substance, and serve as the yard stick for the value of our proposals. Lately, the field of cryptography has seen a sharp increase in the number of new assumptions that are often complex to define and difficult to interpret. At times, these assumptions are hard to untangle from the constructions which utilize them. We believe that the lack of standards of what is accepted as a reasonable cryptographic assumption can be harmful to the credibility of our field. Therefore, there is a great need for measures according to which we classify and compare assumptions, as to which are safe and which are not. In this paper, we propose such a classification and review recently suggested assumptions in this light. This follows the footsteps of Naor Crypto 2003. Our governing principle is relying on hardness assumptions that are independent of the cryptographic constructions.

This paper puts across the various approaches and methods that have been proposed in the context of Fuzzy Mathematical Morphology. The underlying principles of Dilation & Erosion, the structuring elements used in various techniques, the unique variations put forth by researchers, new applications in spatial relationships, decision making, segmentation of medical images have been discussed.

In a recent paper (Computer Aided Geometric Design 23 (3), 243-260), Yang presented a novel kind of nonlinear and geometry driven subdivision scheme for curve interpolation. The author declared that this scheme was shape preserving when all free parameters were explicitly selected by some specific rules. In this note, we demonstrate that the author (a) ignored the consistency of the definition to straight edges, and also (b) did not give a perfect scheme and proof for the shape preserving subdivision.

In this paper we present a new semantics, called Local Models Semantics, and use it to provide a foundation to reasoning with contexts. This semantics captures and makes precise the two main intuitions underlying contextual reasoning: (i) reasoning is mainly local and uses only part of what is potentially available (e.g., what is known, the available inference procedures), this part is what we call context (of reasoning); however (ii) there is compatibility among the reasoning performed in different contexts. We validate our semantics by formalizing two important forms of contextual reasoning: reasoning with viewpoints and reasoning about belief.

Summary: The Big Five factors structure is currently the benchmark for personality dimensions. In the domain of adjectives, various instruments have been developed to measure the Big Five. In this contribution we propose a methodology to find a simple factorial structure and we apply this methodology to the domain of Big Five as measured by adjectives. Using data collected on a sample of 337 subjects, we propose a five-factor benchmark structure derived from the 50 best marker adjectives selected among the adjectives contained in three instruments specifically developed to measure the Big Five (i.e., Goldberg 's 100 adjectives list, IASR-B5, and SACBIF). We use this common factor structure (or benchmark structure) to investigate the differences and the similarities between the three operationalizations of the Big Five, and to investigate the placements of the full set of adjectives contained in the three instruments. The main features of the proposed methodology and the generalizability of the obtained results are discussed.

Based on fuzzy clustering, a new ensemble method of Bagging F-Bagging is proposed in this paper. Firstly the training data are clustered using fuzzy clustering, and then according to the matrix, dividing the training samples into subset intersect, at last each subset of the data are trained, and proper weighted method is used to base learners. As each subset contains different categories and different training data, thus the members of the classifier are diverse. The number of subsets determines the number of the base learners. Experimental results show that this approach can achieve good results.

The notion of boosting originated in the Machine Learning literature in the 1980's [VALIANT, L.G. (1984). A theory of the learnable. In Proc. 16th Annual ACM Symposium on Theory of Computing 436-445. ACM Press, New York]. The goal of boosting is to improve the generalization performance of weak (or base) learning algorithms by combining them in a certain way. The first algorithm of this type was discovered by Schapire [SCHAPIRE, R.E. (1990). The strength of weak learnability. Machine Learning 5 197-227] and then the second one by Freund [FREUND, Y. (1995). Boosting a weak learning algorithm by majority. Inform. and Comput. 121 256-285]. Schapire and Freund [FREUND, Y. and Schapire. R.E. (1997). A decision-theoretic generalization of on-line learning and an application to boosting. J. Comput. System. Sci. 55 119-139] came up with the idea of a more practical version of boosting and invented the algorithm called AdaBoost that combines simple classification rules into much more powerful and precise classification algorithms. For a fixed number of iterations, AdaBoost runs the weak (or base) learning algorithm on resampled original data sets in a sequential manner and then combines the resulting learning algorithms through a weighted summation at the end of the iteration. Gradually, it became clear that AdaBoost is a special case of a more general statistical methodology of combining simple estimates in classification or regression into more complex and more precise ones. The study of statistical properties of these methods has been conducted in several directions since then in both the machine learning and statistics communities. ¶ The problem of consistency of AdaBoost is posed by Leo Breiman in the first paper in this issue of The Annals of Statistics. Breiman studies one ingredient needed to prove the consistency, the convergence properties of AdaBoost as a numerical method in the population case. This paper has been circulated for a couple of years as a preprint and its results were also covered in the Wald Lectures delivered by Breiman at the IMS Annual Meeting in 2002 in Banff, Canada. The papers by Jiang, Lugosi and Vayatis, and Zhang, published below with discussions, consider various versions of boosting and give answers to the consistency question posed by Breiman.

Secondary 5 students from four schools in Hong Kong were required to classify 18 paper and pencil physics problems in terms of whether the problems contain necessary and sufficient, missing or irrelevant information for their solution. Students' ability to denote missing information correlated rather highly with the solution rates of the problems. In another test, students were asked to classify whether the problems in each of six pairs were similar to or different from each other according to students' self-determined criteria. Students who used a deep structure (i.e. used the underlying physics principles) to classify the problems have significantly higher scores in detecting missing and irrelevant information and in the solution rates than those who used surface structure or features for classification. It is argued that a student who is able to identify what information is sufficient, missing or irrelevant for solving a problem understands the problem structure and so is better able to solve it. Such a student is likely to adopt a deep structure in categorizing physics problems. This latter result corroborates with the findings of the expert-novice research paradigm.

Publisher Summary This chapter focuses on dynamic interpretation, negation, and VP-anaphora. It discusses the Dynamic Montague Grammar formalism (DMG), and its semantic representation language into the analysis of VP-Ellipsis in Catalan language, following Gardent's version and to adapt this approach to those elliptical constructs that interact with the Negative Polarity Operator (NPO). It is generally accepted that VP-Ellipsis is a kind of anaphora. This means that it is necessary to identify those parameters leading to the retrieval of a previously uttered entity because of which the anaphor is interpretable. As for VP-Ellipsis, the process consists of the suppression of the verb and its complements in the ellipsis, leaving no other evidence in the ellipsis clause than an auxiliary verb—in English—and adverbial modifiers—in Catalan. The antecedent clause (a-clause) will in this way modify the interpretation of the ellipsis clause (e-clause); at the same time, the a-clause interpretation will be possible with the help of a property or relationship that seems to be identical to the property or relationship expressed in the e-clause.

The program for the 2008 Joint Mathematics Meetings in San Diego contains a contributed papers session Cryptology for Undergraduates on the morning of Wednesday, January 9, 2008. The session is bei...

Machine learning (ML) has pervaded most areas of protein engineering, including stability and stereoselectivity. Using limonene epoxide hydrolase as the model enzyme and innov'SAR as the ML platform, comprising a digital signal process, we achieved high protein robustness that can resist unfolding with concomitant detrimental aggregation. Fourier transform (FT) allows us to take into account the order of the protein sequence and the nonlinear interactions between positions, and thus to grasp epistatic phenomena. The innov'SAR approach is interpolative, extrapolative and makes outside‐the‐box, predictions not found in other state‐of‐the‐art ML or deep learning approaches. Equally significant is the finding that our approach to ML in the present context, flanked by advanced molecular dynamics simulations, uncovers the connection between epistatic mutational interactions and protein robustness., A quick learner: Machine learning based on the innov'SAR algorithm leads to efficient selection of highly robust limonene epoxide hydrolase mutants with enhanced unfolding stability and resistance to aggregation by recognizing epistatic mutational interactions.

In drug development decision-making is often supported through model-based methods, such as physiologically-based pharmacokinetics (PBPK). Global sensitivity analysis (GSA) is gaining use for quality assessment of model-informed inference. However, the inclusion and interpretation of correlated factors in GSA has proven an issue. Here we developed and evaluated a latent variable approach for dealing with correlated factors in GSA. An approach was developed that describes the correlation between two model inputs through the causal relationship of three independent factors: the latent variable and the unique variances of the two correlated parameters. The latent variable approach was applied to a set of algebraic models and a case from PBPK. Then, this method was compared to Sobol’s GSA assuming no correlations, Sobol’s GSA with groups and the Kucherenko approach. For the latent variable approach, GSA was performed with Sobol’s method. By using the latent variable approach, it is possible to devise a unique and easy interpretation of the sensitivity indices while maintaining the correlation between the factors. Compared methods either consider the parameters independent, group the dependent variables into one unique factor or present difficulties in the interpretation of the sensitivity indices. In situations where GSA is called upon to support model-informed decision-making, the latent variable approach offers a practical method, in terms of ease of implementation and interpretability, for applying GSA to models with correlated inputs that does not violate the independence assumption. Prerequisites and limitations of the approach are discussed. Supplementary Information The online version supplementary material available at 10.1007/s10928-021-09764-x.

PURPOSE In rapidly acquired functional MRI (fast fMRI) data, the noise serial correlations (SC) can produce problematically overestimated T-statistics which lead to invalid statistical inferences. This study aims to evaluate and improve the accuracy of high-order autoregressive model (AR(p), where p is the model order) based prewhitening method in the SC correction. METHODS Fast fMRI images were acquired at rest (null data) using a multiband simultaneous multi-slice echo planar imaging pulse sequence with repetition time (TR) = 300 and 500 ms. The SC effect in the fast fMRI data was corrected using the prewhitening method based on two AR(p) models: (1) the conventional model (fixed AR(p)) which preselects a constant p for all the image voxels; (2) an improved model (ARAICc ) that employs the corrected Akaike information criterion voxel-wise to automatically select the model orders for each voxel. To evaluate accuracy of SC correction, false positive characteristics were measured by assuming the presence of block and event-related tasks in the null data without image smoothing. The performance of prewhitening was also examined in smoothed images by adding pseudo task fMRI signals into the null data and comparing the detected to simulated activations (ground truth). RESULTS The measured false positive characteristics agreed well with the theoretical curve when using the ARAICc , and the activation maps in the smoothed data matched the ground truth. The ARAICc showed improved performance than the fixed AR(p) method. CONCLUSION The ARAICc can effectively remove noise SC, and accurate statistical analysis results can be obtained with the ARAICc correction in fast fMRI.

COVID-19 pandemic has affected all aspects of people's lives and disrupted the economy. Forecasting the number of cases infected with this virus can help authorities make accurate decisions on the interventions that must be implemented to control the pandemic. Investigation of the studies on COVID-19 forecasting indicates that various techniques such as statistical, mathematical, and machine and deep learning have been utilized. Although deep learning models have shown promising results in this context, their performance can be improved using auxiliary features. Therefore, in this study, we propose two hybrid deep learning methods that utilize the statistical features as auxiliary inputs and associate them with their main input. Specifically, we design a hybrid method of the multihead attention mechanism and the statistical features (ATT_FE) and a combined method of convolutional neural network and the statistical features (CNN_FE) and apply them to COVID-19 data of 10 countries with the highest number of confirmed cases. The results of experiments indicate that the hybrid models outperform their conventional counterparts in terms of performance measures. The experiments also demonstrate the superiority of the hybrid ATT_FE method over the long short-term memory model.

PURPOSE Intravoxel incoherent motion (IVIM) analysis gives information on tissue diffusion and perfusion and may thus have a potential for e.g. tumor tissue characterization. This work aims to study if clustering based on IVIM parameter maps can identify tumor subregions, and to assess the relevance of obtained subregions by histological analysis. METHODS Fourteen mice with human neuroendocrine tumors were examined with diffusion-weighted imaging to obtain IVIM parameter maps. Gaussian mixture models with IVIM maps from all tumors as input were used to partition voxels into k clusters, where k = 2 was chosen for further analysis based on goodness of fit. Clustering was performed with and without the perfusion-related IVIM parameter D* , and with and without including spatial information. The validity of the clustering was assessed by comparison with corresponding histologically stained tumor sections. A Ki-67-based index quantifying the degree of tumor proliferation was considered appropriate for the comparison based on the obtained cluster characteristics. RESULTS The clustering resulted in one class with low diffusion and high perfusion and another with slightly higher diffusion and low perfusion. Strong agreement was found between tumor subregions identified by clustering and subregions identified by histological analysis, both regarding size and spatial agreement. Neither D* nor spatial information had substantial effects on the clustering results. CONCLUSIONS The results of this study show that IVIM parameter maps can be used to identify tumor subregions using a data-driven framework based on Gaussian mixture models. In the studied tumor model, the obtained subregions showed agreement with proliferative activity.

Background Advanced prediction of the daily incidence of COVID-19 can aid policy making on the prevention of disease spread, which can profoundly affect people's livelihood. In previous studies, predictions were investigated for single or several countries and territories. Objective We aimed to develop models that can be applied for real-time prediction of COVID-19 activity in all individual countries and territories worldwide. Methods Data of the previous daily incidence and infoveillance data (search volume data via Google Trends) from 215 individual countries and territories were collected. A random forest regression algorithm was used to train models to predict the daily new confirmed cases 7 days ahead. Several methods were used to optimize the models, including clustering the countries and territories, selecting features according to the importance scores, performing multiple-step forecasting, and upgrading the models at regular intervals. The performance of the models was assessed using the mean absolute error (MAE), root mean square error (RMSE), Pearson correlation coefficient, and Spearman correlation coefficient. Results Our models can accurately predict the daily new confirmed cases of COVID-19 in most countries and territories. Of the 215 countries and territories under study, 198 (92.1%) had MAEs 0.8. For the 215 countries and territories, the mean MAE was 5.42 (range 0.26-15.32), the mean RMSE was 9.27 (range 1.81-24.40), the mean Pearson correlation coefficient was 0.89 (range 0.08-0.99), and the mean Spearman correlation coefficient was 0.84 (range 0.2-1.00). Conclusions By integrating previous incidence and Google Trends data, our machine learning algorithm was able to predict the incidence of COVID-19 in most individual countries and territories accurately 7 days ahead.

Publisher Summary This chapter focuses on connection theory of children's language and linguistic theory. It discusses the problem of a child's recognition of nonuniversal aspects of deep structure. It is not the case that deep structure is the same for all languages. Grammatical relations are, by hypothesis, universal, but the order of elements is not. It is not the case that simple, active, declarative sentences always reflect deep structure order directly. It is not the case that the most frequent forms in surface structure reflect deep structure. Traditionally, the determination of base word order depends upon analysis of the transformational component. The most important transformation in German is the verb-second transformation which transfers an element from final position to second position in the creation of declarative sentences. It is the broad applicability of this transformation that makes elegantly simple a description of German that uses a verb-final base structure. The subordinate-clause strategy is a powerful mechanism for the discovery of deep structure.

// Qi Zhao 1, 2 , Di Xie 1 , Hongsheng Liu 2, 3 , Fan Wang 4, 5 , Gui-Ying Yan 6 and Xing Chen 7 1 School of Mathematics, Liaoning University, Shenyang, China 2 Research Center for Computer Simulating and Information Processing of Bio-Macromolecules of Liaoning Province, Shenyang, China 3 School of Life Science, Liaoning University, Shenyang, China 4 School of Mechatronic Engineering, China University of Mining and Technology, Xuzhou, China 5 Jiangsu Key Laboratory of Mine Mechanical and Electrical Equipment, China University of Mining and Technology, Xuzhou, China 6 Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China 7 School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, China Correspondence to: Qi Zhao, email: zhaoqi@lnu.edu.cn Xing Chen, email: xingchen@amss.ac.cn Keywords: microRNA; disease; association prediction; spy strategy; super cluster strategy Received: July 18, 2017 Accepted: October 30, 2017 Published: December 01, 2017 ABSTRACT In the biological field, the identification of the associations between microRNAs (miRNAs) and diseases has been paid increasing attention as an extremely meaningful study for the clinical medicine. However, it is expensive and time-consuming to confirm miRNA-disease associations by experimental methods. Therefore, in recent years, several effective computational models for predicting the potential miRNA-disease associations have been developed. In this paper, we proposed the Spy and Super Cluster strategy for MiRNA-Disease Association prediction (SSCMDA) based on known miRNA-disease associations, integrated disease similarity and integrated miRNA similarity. For problems of mixed unknown miRNA-disease pairs containing both potential associations and real negative associations, which will lead to inaccurate prediction, spy strategy is adopted by SSCMDA to identify reliable negative samples from the unknown miRNA-disease pairs. Moreover, the super-cluster strategy could gather as many positive samples as possible to improve the accuracy of the prediction by overcoming the shortage of lacking sufficient positive training samples. As a result, the AUCs of global leave-one-out cross validation (LOOCV), local LOOCV and 5-fold cross validation were 0.9007, 0.8747 and 0.8806+/-0.0025, respectively. According to the AUC results, SSCMDA has shown a significant improvement compared with some previous models. We further carried out case studies based on various version of HMDD database to test the prediction performance robustness of SSCMDA. We also implemented case study to examine whether SSCMDA was effective for new diseases without any known associated miRNAs. As a result, a large proportion of the predicted miRNAs have been verified by experimental reports.

Background Wearable devices have been widely used in clinical studies to study daily activity patterns, but the analysis remains a major obstacle for researchers. Objective This study proposes a novel method to characterize sleep-activity rhythms using actigraphy and further use it to describe early childhood daily rhythm formation and examine its association with physical development. Methods We developed a machine learning–based Penalized Multiband Learning (PML) algorithm to sequentially infer dominant periodicities based on the Fast Fourier Transform (FFT) algorithm and further characterize daily rhythms. We implemented and applied the algorithm to Actiwatch data collected from a cohort of 262 healthy infants at ages 6, 12, 18, and 24 months, with 159, 101, 111, and 141 participants at each time point, respectively. Autocorrelation analysis and Fisher test in harmonic analysis with Bonferroni correction were applied for comparison with the PML. The association between activity rhythm features and early childhood motor development, assessed using the Peabody Developmental Motor Scales-Second Edition (PDMS-2), was studied through linear regression analysis. Results The PML results showed that 1-day periodicity was most dominant at 6 and 12 months, whereas one-day, one-third–day, and half-day periodicities were most dominant at 18 and 24 months. These periodicities were all significant in the Fisher test, with one-fourth–day periodicity also significant at 12 months. Autocorrelation effectively detected 1-day periodicity but not the other periodicities. At 6 months, PDMS-2 was associated with the assessment seasons. At 12 months, PDMS-2 was associated with the assessment seasons and FFT signals at one-third–day periodicity (P Conclusions The proposed PML algorithm can effectively conduct circadian rhythm analysis using time-series wearable device data. The application of the method effectively characterized sleep-wake rhythm development and identified the association between daily rhythm formation and motor development during early childhood.

Motivation: Imaging genetics combines brain imaging and genetic information to identify the relationships between genetic variants and brain activities. When the data samples belong to different classes (e.g. disease status), the relationships may exhibit class-specific patterns that can be used to facilitate the understanding of a disease. Conventional approaches often perform separate analysis on each class and report the differences, but ignore important shared patterns. Results: In this paper, we develop a multivariate method to analyze the differential dependency across multiple classes. We propose a joint sparse canonical correlation analysis method, which uses a generalized fused lasso penalty to jointly estimate multiple pairs of canonical vectors with both shared and class-specific patterns. Using a data fusion approach, the method is able to detect differentially correlated modules effectively and efficiently. The results from simulation studies demonstrate its higher accuracy in discovering both common and differential canonical correlations compared to conventional sparse CCA. Using a schizophrenia dataset with 92 cases and 116 controls including a single nucleotide polymorphism (SNP) array and functional magnetic resonance imaging data, the proposed method reveals a set of distinct SNP-voxel interaction modules for the schizophrenia patients, which are verified to be both statistically and biologically significant. Availability and Implementation: The Matlab code is available at https://sites.google.com/site/jianfang86/JSCCA. Contact: wyp@tulane.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Motivation Integration of different omics data could markedly help to identify biological signatures, understand the missing heritability of complex diseases and ultimately achieve personalized medicine. Standard regression models used in Genome-Wide Association Studies (GWAS) identify loci with a strong effect size, whereas GWAS meta-analyses are often needed to capture weak loci contributing to the missing heritability. Development of novel machine learning algorithms for merging genotype data with other omics data is highly needed as it could enhance the prioritization of weak loci. Results We developed cNMTF (corrected non-negative matrix tri-factorization), an integrative algorithm based on clustering techniques of biological data. This method assesses the inter-relatedness between genotypes, phenotypes, the damaging effect of the variants and gene networks in order to identify loci-trait associations. cNMTF was used to prioritize genes associated with lipid traits in two population cohorts. We replicated 129 genes reported in GWAS world-wide and provided evidence that supports 85% of our findings (226 out of 265 genes), including recent associations in literature (NLGN1), regulators of lipid metabolism (DAB1) and pleiotropic genes for lipid traits (CARM1). Moreover, cNMTF performed efficiently against strong population structures by accounting for the individuals’ ancestry. As the method is flexible in the incorporation of diverse omics data sources, it can be easily adapted to the user’s research needs. Availability and implementation An R package (cnmtf) is available at https://lgl15.github.io/cnmtf_web/index.html. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation: Somatic copy number aberrations (SCNAs) are frequent in cancer genomes, but many of these are random, passenger events. A common strategy to distinguish functional aberrations from passengers is to identify those aberrations that are recurrent across multiple samples. However, the extensive variability in the length and position of SCNAs makes the problem of identifying recurrent aberrations notoriously difficult. Results: We introduce a combinatorial approach to the problem of identifying independent and recurrent SCNAs, focusing on the key challenging of separating the overlaps in aberrations across individuals into independent events. We derive independent and recurrent SCNAs as maximal cliques in an interval graph constructed from overlaps between aberrations. We efficiently enumerate all such cliques, and derive a dynamic programming algorithm to find an optimal selection of non-overlapping cliques, resulting in a very fast algorithm, which we call RAIG (Recurrent Aberrations from Interval Graphs). We show that RAIG outperforms other methods on simulated data and also performs well on data from three cancer types from The Cancer Genome Atlas (TCGA). In contrast to existing approaches that employ various heuristics to select independent aberrations, RAIG optimizes a well-defined objective function. We show that this allows RAIG to identify rare aberrations that are likely functional, but are obscured by overlaps with larger passenger aberrations. Availability: http://compbio.cs.brown.edu/software. Contact: braphael@brown.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Background Physical activity (PA) level is associated with multiple health benefits during early childhood. However, inconsistency in the methods for quantification of PA levels among preschoolers remains a problem. Objective This study aimed to develop PA intensity cut points for wrist-worn accelerometers by using machine learning (ML) approaches to assess PA in preschoolers. Methods Wrist- and hip-derived acceleration data were collected simultaneously from 34 preschoolers on 3 consecutive preschool days. Two supervised ML models, receiver operating characteristic curve (ROC) and ordinal logistic regression (OLR), and one unsupervised ML model, k-means cluster analysis, were applied to establish wrist-worn accelerometer vector magnitude (VM) cut points to classify accelerometer counts into sedentary behavior, light PA (LPA), moderate PA (MPA), and vigorous PA (VPA). Physical activity intensity levels identified by hip-worn accelerometer VM cut points were used as reference to train the supervised ML models. Vector magnitude counts were classified by intensity based on three newly established wrist methods and the hip reference to examine classification accuracy. Daily estimates of PA were compared to the hip-reference criterion. Results In total, 3600 epochs with matched hip- and wrist-worn accelerometer VM counts were analyzed. All ML approaches performed differently on developing PA intensity cut points for wrist-worn accelerometers. Among the three ML models, k-means cluster analysis derived the following cut points: ≤2556 counts per minute (cpm) for sedentary behavior, 2557-7064 cpm for LPA, 7065-14532 cpm for MPA, and ≥14533 cpm for VPA; in addition, k-means cluster analysis had the highest classification accuracy, with more than 70% of the total epochs being classified into the correct PA categories, as examined by the hip reference. Additionally, k-means cut points exhibited the most accurate estimates on sedentary behavior, LPA, and VPA as the hip reference. None of the three wrist methods were able to accurately assess MPA. Conclusions This study demonstrates the potential of ML approaches in establishing cut points for wrist-worn accelerometers to assess PA in preschoolers. However, the findings from this study warrant additional validation studies.

Coniferous trees such as eucalyptus used to be preferred for papermaking because the cellulose fiber in the pulp of these species are longer, therefore making for stronger paper. In this study, the proposed neural network method solves in an efficient way, how to build prediction models in engineering. The system has been applied to predict amount of wood for production of paper, in which the coefficients can explain the variable with more influence over the variable to forecast. Obtaining a good prediction and as simple as possible, i.e. with the least number of forecast variables.

Motivation: Loops in proteins are often involved in biochemical functions. Their irregularity and flexibility make experimental structure determination and computational modeling challenging. Most current loop modeling methods focus on modeling single loops. In protein structure prediction, multiple loops often need to be modeled simultaneously. As interactions among loops in spatial proximity can be rather complex, sampling the conformations of multiple interacting loops is a challenging task. Results: In this study, we report a new method called multi-loop Distance-guided Sequential chain-Growth Monte Carlo (M-DiSGro) for prediction of the conformations of multiple interacting loops in proteins. Our method achieves an average RMSD of 1.93 Å for lowest energy conformations of 36 pairs of interacting protein loops with the total length ranging from 12 to 24 residues. We further constructed a data set containing proteins with 2, 3 and 4 interacting loops. For the most challenging target proteins with four loops, the average RMSD of the lowest energy conformations is 2.35 Å. Our method is also tested for predicting multiple loops in β-barrel membrane proteins. For outer-membrane protein G, the lowest energy conformation has a RMSD of 2.62 Å for the three extracellular interacting loops with a total length of 34 residues (12, 12 and 10 residues in each loop). Availability and implementation: The software is freely available at: tanto.bioe.uic.edu/m-DiSGro. Contact: jinfeng@stat.fsu.edu or jliang@uic.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Motivation: Similarity search is the foundation of bioinformatics. It plays a key role in establishing structural, functional and evolutionary relationships between biological sequences. Although the power of the similarity search has increased steadily in recent years, a high percentage of sequences remain uncharacterized in the protein universe. Thus, new similarity search strategies are needed to efficiently and reliably infer the structure and function of new sequences. The existing paradigm for studying protein sequence, structure, function and evolution has been established based on the assumption that the protein universe is discrete and hierarchical. Cumulative evidence suggests that the protein universe is continuous. As a result, conventional sequence homology search methods may be not able to detect novel structural, functional and evolutionary relationships between proteins from weak and noisy sequence signals. To overcome the limitations in existing similarity search methods, we propose a new algorithmic framework—Enrichment of Network Topological Similarity (ENTS)—to improve the performance of large scale similarity searches in bioinformatics. Results: We apply ENTS to a challenging unsolved problem: protein fold recognition. Our rigorous benchmark studies demonstrate that ENTS considerably outperforms state-of-the-art methods. As the concept of ENTS can be applied to any similarity metric, it may provide a general framework for similarity search on any set of biological entities, given their representation as a network. Availability and implementation: Source code freely available upon request Contact: lxie@iscb.org

For the last decades, research studies have been developed in which a coalition of Fuzzy Sets Theory and Statistics has been established with different purposes. These namely are: (i) to introduce new data analysis problems in which the objective involves either fuzzy relationships or fuzzy terms; (ii) to establish well-formalized models for elements combining randomness and fuzziness; (iii) to develop uni- and multivariate statistical methodologies to handle fuzzy-valued data; and (iv) to incorporate fuzzy sets to help in solving traditional statistical problems with non-fuzzy data. In spite of a growing literature concerning the development and application of fuzzy techniques in statistical analysis, the need is felt for a more systematic insight into the potentialities of cross fertilization between Statistics and Fuzzy Logic. In line with the synergistic spirit of Soft Computing, some instances of the existing research activities on the topic are recalled. Particular attention is paid to summarize the papers gathered in this Special Issue, ranging from the position paper on the theoretical management of uncertainty by the "father" of Fuzzy Logic to a wide diversity of topics concerning foundational/methodological/applied aspects of the integration of Fuzzy Sets and Statistics. (C) 2006 Elsevier B.V. All rights reserved.

In order to improve docking score correction, we developed several structure‐based quantitative structure activity relationship (QSAR) models by protein‐drug docking simulations and applied these models to public affinity data. The prediction models used descriptor‐based regression, and the compound descriptor was a set of docking scores against multiple (∼600) proteins including nontargets. The binding free energy that corresponded to the docking score was approximated by a weighted average of docking scores for multiple proteins, and we tried linear, weighted linear and polynomial regression models considering the compound similarities. In addition, we tried a combination of these regression models for individual data sets such as IC50, Ki, and %inhibition values. The cross‐validation results showed that the weighted linear model was more accurate than the simple linear regression model. Thus, the QSAR approaches based on the affinity data of public databases should improve docking scores.

Motivation: Proteins and protein complexes coordinate their activity to execute cellular functions. In a number of experimental settings, including synthetic genetic arrays, genetic perturbations and RNAi screens, scientists identify a small set of protein interactions of interest. A working hypothesis is often that these interactions are the observable phenotypes of some functional process, which is not directly observable. Confirmatory analysis requires finding other pairs of proteins whose interaction may be additional phenotypical evidence about the same functional process. Extant methods for finding additional protein interactions rely heavily on the information in the newly identified set of interactions. For instance, these methods leverage the attributes of the individual proteins directly, in a supervised setting, in order to find relevant protein pairs. A small set of protein interactions provides a small sample to train parameters of prediction methods, thus leading to low confidence. Results: We develop RBSets, a computational approach to ranking protein interactions rooted in analogical reasoning; that is, the ability to learn and generalize relations between objects. Our approach is tailored to situations where the training set of protein interactions is small, and leverages the attributes of the individual proteins indirectly, in a Bayesian ranking setting that is perhaps closest to propensity scoring in mathematical psychology. We find that RBSets leads to good performance in identifying additional interactions starting from a small evidence set of interacting proteins, for which an underlying biological logic in terms of functional processes and signaling pathways can be established with some confidence. Our approach is scalable and can be applied to large databases with minimal computational overhead. Our results suggest that analogical reasoning within a Bayesian ranking problem is a promising new approach for real-time biological discovery. Availability: Java code is available at: www.gatsby.ucl.ac.uk/~rbas. Contact: airoldi@fas.harvard.edu; kheller@mit.edu; ricardo@stats.ucl.ac.uk

Motivation We introduce PRINCESS, a privacy-preserving international collaboration framework for analyzing rare disease genetic data that are distributed across different continents. PRINCESS leverages Software Guard Extensions (SGX) and hardware for trustworthy computation. Unlike a traditional international collaboration model, where individual-level patient DNA are physically centralized at a single site, PRINCESS performs a secure and distributed computation over encrypted data, fulfilling institutional policies and regulations for protected health information. Results To demonstrate PRINCESS’ performance and feasibility, we conducted a family-based allelic association study for Kawasaki Disease, with data hosted in three different continents. The experimental results show that PRINCESS provides secure and accurate analyses much faster than alternative solutions, such as homomorphic encryption and garbled circuits (over 40 000× faster). Availability and Implementation https://github.com/achenfengb/PRINCESS_opensource Supplementary information Supplementary data are available at Bioinformatics online.

The aim of this work is to develop a tool to predict some pulp properties e.g., pulp yield, Kappa number, ISO brightness (ISO 2470:2008), fiber length and fiber width, using the sapwood and heartwood proportion in the raw-material. For this purpose, Acacia melanoxylon trees were collected from four sites in Portugal. Percentage of sapwood and heartwood, area and the stem eccentricity (in N-S and E-W directions) were measured on transversal stem sections of A. melanoxylon R. Br. The relative position of the samples with respect to the total tree height was also considered as an input variable. Different configurations were tested until the maximum correlation coefficient was achieved. A classical mathematical technique (multiple linear regression) and machine learning methods (classification and regression trees, multi-layer perceptron and support vector machines) were tested. Classification and regression trees (CART) was the most accurate model for the prediction of pulp ISO brightness (R = 0.85). The other parameters could be predicted with fair results (R = 0.64–0.75) by CART. Hence, the proportion of heartwood and sapwood is a relevant parameter for pulping and pulp properties, and should be taken as a quality trait when assessing a pulpwood resource. info:eu-repo/semantics/acceptedVersion

Motivation The identification of heterogeneities in cell populations by utilizing single-cell technologies such as single-cell RNA-Seq, enables inference of cellular development and lineage trees. Several methods have been proposed for such inference from high-dimensional single-cell data. They typically assign each cell to a branch in a differentiation trajectory. However, they commonly assume specific geometries such as tree-like developmental hierarchies and lack statistically sound methods to decide on the number of branching events. Results We present K-Branches, a solution to the above problem by locally fitting half-lines to single-cell data, introducing a clustering algorithm similar to K-Means. These halflines are proxies for branches in the differentiation trajectory of cells. We propose a modified version of the GAP statistic for model selection, in order to decide on the number of lines that best describe the data locally. In this manner, we identify the location and number of subgroups of cells that are associated with branching events and full differentiation, respectively. We evaluate the performance of our method on single-cell RNA-Seq data describing the differentiation of myeloid progenitors during hematopoiesis, single-cell qPCR data of mouse blastocyst development, single-cell qPCR data of human myeloid monocytic leukemia and artificial data. Availability and implementation An R implementation of K-Branches is freely available at https://github.com/theislab/kbranches. Supplementary information Supplementary data are available at Bioinformatics online.

Motivation: The network architecture of physical protein interactions is an important determinant for the molecular functions that are carried out within each cell. To study this relation, the network architecture can be characterized by graph topological characteristics such as shortest paths and network hubs. These characteristics have an important shortcoming: they do not take into account that interactions occur across different scales. This is important because some cellular functions may involve a single direct protein interaction (small scale), whereas others require more and/or indirect interactions, such as protein complexes (medium scale) and interactions between large modules of proteins (large scale). Results: In this work, we derive generalized scale-aware versions of known graph topological measures based on diffusion kernels. We apply these to characterize the topology of networks across all scales simultaneously, generating a so-called graph topological scale-space. The comprehensive physical interaction network in yeast is used to show that scale-space based measures consistently give superior performance when distinguishing protein functional categories and three major types of functional interactions—genetic interaction, co-expression and perturbation interactions. Moreover, we demonstrate that graph topological scale spaces capture biologically meaningful features that provide new insights into the link between function and protein network architecture., Bioinformatics, 30 (12), ISSN:1367-4803, ISSN:1460-2059

Motivation Codon models are widely used to identify the signature of selection at the molecular level and to test for changes in selective pressure during the evolution of genes encoding proteins. The large size of the state space of the Markov processes used to model codon evolution makes it difficult to use these models with large biological datasets. We propose here to use state aggregation to reduce the state space of codon models and, thus, improve the computational performance of likelihood estimation on these models. Results We show that this heuristic speeds up the computations of the M0 and branch-site models up to 6.8 times. We also show through simulations that state aggregation does not introduce a detectable bias. We analyzed a real dataset and show that aggregation provides highly correlated predictions compared to the full likelihood computations. Finally, state aggregation is a very general approach and can be applied to any continuous-time Markov process-based model with large state space, such as amino acid and coevolution models. We therefore discuss different ways to apply state aggregation to Markov models used in phylogenetics. Availability and Implementation The heuristic is implemented in the godon package (https://bitbucket.org/Davydov/godon) and in a version of FastCodeML (https://gitlab.isb-sib.ch/phylo/fastcodeml). Supplementary information Supplementary data are available at Bioinformatics online.

Quantitative computed tomography-based finite-element analysis (QCT/FEA) has become increasingly popular in an attempt to understand and possibly reduce vertebral fracture risk. It is known that scanning acquisition settings affect Hounsfield units (HU) of the CT voxels. Material properties assignments in QCT/FEA, relating HU to Young's modulus, are performed by applying empirical equations. The purpose of this study was to evaluate the effect of QCT scanning protocols on predicted stiffness values from finite-element models. One fresh frozen cadaveric torso and a QCT calibration phantom were scanned six times varying voltage and current and reconstructed to obtain a total of 12 sets of images. Five vertebrae from the torso were experimentally tested to obtain stiffness values. QCT/FEA models of the five vertebrae were developed for the 12 image data resulting in a total of 60 models. Predicted stiffness was compared to the experimental values. The highest percent difference in stiffness was approximately 480% (80 kVp, 110 mAs, U70), while the lowest outcome was ∼1% (80 kVp, 110 mAs, U30). There was a clear distinction between reconstruction kernels in predicted outcomes, whereas voltage did not present a clear influence on results. The potential of QCT/FEA as an improvement to conventional fracture risk prediction tools is well established. However, it is important to establish research protocols that can lead to results that can be translated to the clinical setting.

Motivation: The analysis of differentially expressed gene sets became a routine in the analyses of gene expression data. There is a multitude of tests available, ranging from aggregation tests that summarize gene-level statistics for a gene set to true multivariate tests, accounting for intergene correlations. Most of them detect complex departures from the null hypothesis but when the null hypothesis is rejected, the specific alternative leading to the rejection is not easily identifiable. Results: In this article we compare the power and Type I error rates of minimum-spanning tree (MST)-based non-parametric multivariate tests with several multivariate and aggregation tests, which are frequently used for pathway analyses. In our simulation study, we demonstrate that MST-based tests have power that is for many settings comparable with the power of conventional approaches, but outperform them in specific regions of the parameter space corresponding to biologically relevant configurations. Further, we find for simulated and for gene expression data that MST-based tests discriminate well against shift and scale alternatives. As a general result, we suggest a two-step practical analysis strategy that may increase the interpretability of experimental data: first, apply the most powerful multivariate test to find the subset of pathways for which the null hypothesis is rejected and second, apply MST-based tests to these pathways to select those that support specific alternative hypotheses. Contact:gvglazko@uams.edu or yrahmatallah@uams.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Motivation: Burgeoning sequencing technologies have generated massive amounts of genomic and proteomic data. Annotating the functions of proteins identified in this data has become a big and crucial problem. Various computational methods have been developed to infer the protein functions based on either the sequences or domains of proteins. The existing methods, however, ignore the recurrence and the order of the protein domains in this function inference. Results: We developed two new methods to infer protein functions based on protein domain recurrence and domain order. Our first method, DRDO, calculates the posterior probability of the Gene Ontology terms based on domain recurrence and domain order information, whereas our second method, DRDO-NB, relies on the naïve Bayes methodology using the same domain architecture information. Our large-scale benchmark comparisons show strong improvements in the accuracy of the protein function inference achieved by our new methods, demonstrating that domain recurrence and order can provide important information for inference of protein functions. Availability: The new models are provided as open source programs at http://sfb.kaust.edu.sa/Pages/Software.aspx. Contact: dkihara@cs.purdue.edu, xin.gao@kaust.edu.sa Supplementary information: Supplementary data are available at Bioinformatics Online.

Open Information Extraction (Open IE) is a promising approach for unrestricted Information Discovery (ID). While Open IE is a highly scalable approach, allowing unsupervised relation extraction from open domains, it currently has some limitations. First, it lacks the expressiveness needed to properly represent and extract complex assertions that are abundant in text. Second, it does not consolidate the extracted propositions, which causes simple queries above Open IE assertions to return insufficient or redundant information. To address these limitations, we propose in this position paper a novel representation for ID – Propositional Knowledge Graphs (PKG). PKGs extend the Open IE paradigm by representing semantic inter-proposition relations in a traversable graph. We outline an approach for constructing PKGs from single and multiple texts, and highlight a variety of high-level applications that may leverage PKGs as their underlying information discovery and representation framework.

Motivation: Most functions within the cell emerge thanks to protein–protein interactions (PPIs), yet experimental determination of PPIs is both expensive and time-consuming. PPI networks present significant levels of noise and incompleteness. Predicting interactions using only PPI-network topology (topological prediction) is difficult but essential when prior biological knowledge is absent or unreliable. Methods: Network embedding emphasizes the relations between network proteins embedded in a low-dimensional space, in which protein pairs that are closer to each other represent good candidate interactions. To achieve network denoising, which boosts prediction performance, we first applied minimum curvilinear embedding (MCE), and then adopted shortest path (SP) in the reduced space to assign likelihood scores to candidate interactions. Furthermore, we introduce (i) a new valid variation of MCE, named non-centred MCE (ncMCE); (ii) two automatic strategies for selecting the appropriate embedding dimension; and (iii) two new randomized procedures for evaluating predictions. Results: We compared our method against several unsupervised and supervisedly tuned embedding approaches and node neighbourhood techniques. Despite its computational simplicity, ncMCE-SP was the overall leader, outperforming the current methods in topological link prediction. Conclusion: Minimum curvilinearity is a valuable non-linear framework that we successfully applied to the embedding of protein networks for the unsupervised prediction of novel PPIs. The rationale for our approach is that biological and evolutionary information is imprinted in the non-linear patterns hidden behind the protein network topology, and can be exploited for predicting new protein links. The predicted PPIs represent good candidates for testing in high-throughput experiments or for exploitation in systems biology tools such as those used for network-based inference and prediction of disease-related functional modules. Availability: https://sites.google.com/site/carlovittoriocannistraci/home Contact: moc.liamg@noga.sohtagakolak or as.ude.tsuak@isavar.yhtomit Supplementary information: Supplementary data are available at Bioinformatics online.

A high-resolution whole-body voxel model called CAM representing the Chinese adult male was constructed in this paper based on a previous individual voxel model. There are more than 80 tissues and organs in CAM, including almost all organs required in the ICRP new recommendation. The mass of individual organs has been adjusted to the Chinese reference data. Special considerations were given to representing the gross spatial distribution of various bone constituents as realistically as possible during the construction of the site-specific skeleton. Organ dose conversion coefficients were calculated for six idealized external photon exposures from 10 keV to 10 MeV by using Monte Carlo simulation. The resulting dose coefficients were then compared with those from other models, e.g. CMP, ICRP 74, Rex, HDRK-man and VIP-man. Old and new effective male doses of CAM were calculated by using the tissue weighting factors from ICRP 60 and 103 Publications, respectively. Dosimetric differences between mathematical and voxel models, and the differences between Asian and Caucasian models are also discussed in this paper.

We describe the results of an expert system applied to the evaluation of samples of kaolin for industrial use in paper or ceramic manufacture. Different machine learning techniques—classification trees, support vector machines and Bayesian networks—were applied with the aim of evaluating and comparing their interpretability and prediction capacities. The predictive capacity of these models for the samples analyzed was highly satisfactory, both for ceramic quality and paper quality. However, Bayesian networks generally proved to be the most useful technique for our study, as this approach combines good predictive capacity with excellent interpretability of the kaolin quality structure, as it graphically represents relationships between variables and facilitates what‐if analyses.