ALBERT

Description: In the classic k -center problem, we are given a metric graph, and the objective is to select k nodes as centers such that the maximum distance from any vertex to its closest center is minimized. In this paper, we consider two important generalizations of k -center, the matroid center problem and the knapsack center problem. Both problems are motivated by recent content distribution network applications. Our contributions can be summarized as follows: (1) We consider the matroid center problem in which the centers are required to form an independent set of a given matroid. We show this problem is NP-hard even on a line. We present a 3-approximation algorithm for the problem on general metrics. We also consider the outlier version of the problem where a given number of vertices can be excluded as outliers from the solution. We present a 7-approximation for the outlier version. (2) We consider the (multi-)knapsack center problem in which the centers are required to satisfy one (or more) knapsack constraint(s). It is known that the knapsack center problem with a single knapsack constraint admits a 3-approximation. However, when there are at least two knapsack constraints, we show this problem is not approximable at all. To complement the hardness result, we present a polynomial time algorithm that gives a 3-approximate solution such that one knapsack constraint is satisfied and the others may be violated by at most a factor of \(1+\epsilon \) . We also obtain a 3-approximation for the outlier version that may violate the knapsack constraint by \(1+\epsilon \) .

Description: We design a succinct data structure for representing a poset that, given two elements, can report whether one precedes the other in constant time. This is equivalent to succinctly representing the transitive closure graph of the poset, and we note that the same method can also be used to succinctly represent the transitive reduction graph. For an n element poset, the data structure occupies \(n^2/4 + o(n^2)\) bits in the worst case. Furthermore, a slight extension to this data structure yields a succinct oracle for reachability in arbitrary directed graphs. Thus, using no more than a quarter of the space required to represent an arbitrary directed graph, reachability queries can be supported in constant time. We also consider the operation of listing all the successors or predecessors of a given element, and show how to do this in constant time per element reported using a slightly modified version of our succinct data structure.

Description: We consider a graph observability problem: how many edge colors are needed for an unlabeled graph so that an agent, walking from node to node, can uniquely determine its location from just the observed color sequence of the walk? Specifically, let G ( n ,  d ) be an edge-colored subgraph of d -dimensional (directed or undirected) lattice of size \(n^d = n \times n \times \cdots \times n\) . We say that G ( n ,  d ) is t -observable if an agent can uniquely determine its current position in the graph from the color sequence of any t -dimensional walk, where the dimension is the number of different directions spanned by the edges of the walk. A walk in an undirected lattice G ( n ,  d ) has dimension between 1 and d , but a directed walk can have dimension between 1 and 2 d because of two different orientations for each axis. We derive bounds on the number of colors needed for t -observability. Our main result is that \(\varTheta (n^{d/t})\) colors are both necessary and sufficient for t -observability of G ( n ,  d ), where d is considered a constant. This shows an interesting dependence of graph observability on the ratio between the dimension of the lattice and that of the walk. In particular, the number of colors for full-dimensional walks is \(\varTheta (n^{1/2})\) in the directed case, and \(\varTheta (n)\) in the undirected case, independent of the lattice dimension. All of our results extend easily to non-square lattices: given a lattice graph of size \(N = n_1 \times n_2 \times \cdots \times n_d\) , the number of colors for t -observability is \(\varTheta (\root t \of {N})\) .

Description: Background: With the introduction and implementation of a variety of government programs and policies to encourage adoption of electronic medical records (EMRs), EMRs are being increasingly adopted in North America. We sought to evaluate the completeness of a variety of EMR fields to determine if family physicians were comprehensively using their EMRs and the suitability of use of the data for secondary purposes in Ontario, Canada. Methods: We examined EMR data from a convenience sample of family physicians distributed throughout Ontario within the Electronic Medical Record Administrative data Linked Database (EMRALD) as extracted in the summer of 2012. We identified all physicians with at least one year of EMR use. Measures were developed and rates of physician documentation of clinical encounters, electronic prescriptions, laboratory tests, blood pressure and weight, referrals, consultation letters, and all fields in the cumulative patient profile were calculated as a function of physician and patient time since starting on the EMR. Results: Of the 167 physicians with at least one year of EMR use, we identified 186,237 patients. Overall, the fields with the highest level of completeness were for visit documentations and prescriptions (〉70 %). Improvements were observed with increasing trends of completeness overtime for almost all EMR fields according to increasing physician time on EMR. Assessment of the influence of patient time on EMR demonstrated an increasing likelihood of the population of EMR fields overtime, with the largest improvements occurring between the first and second years. Conclusions: All of the data fields examined appear to be reasonably complete within the first year of adoption with the biggest increase occurring the first to second year. Using all of the basic functions of the EMR appears to be occurring in the current environment of EMR adoption in Ontario. Thus the data appears to be suitable for secondary use.

Description: Background: Recognising the limitations of a paper-based approach to documenting vital sign observations and responding to national clinical guidelines, we have explored the use of an electronic solution that could improve the quality and safety of patient care. We have developed a system for recording vital sign observations at the bedside, automatically calculating an Early Warning Score, and saving data such that it is accessible to all relevant clinicians within a hospital trust. We have studied current clinical practice of using paper observation charts, and attempted to streamline the process. We describe our user-focussed design process, and present the key design decisions prior to describing the system in greater detail. Results: The system has been deployed in three pilot clinical areas over a period of 9 months. During this time, vital sign observations were recorded electronically using our system. Analysis of the number of observations recorded (21,316 observations) and the number of active users (111 users) confirmed that the system is being used for routine clinical observations. Feedback from clinical end-users was collected to assess user acceptance of the system. This resulted in a System Usability Scale score of 77.8, indicating high user acceptability. Conclusions: Our system has been successfully piloted, and is in the process of full implementation throughout adult inpatient clinical areas in the Oxford University Hospitals. Whilst our results demonstrate qualitative acceptance of the system, its quantitative effect on clinical care is yet to be evaluated.

Description: We revisit the matrix problems sparse null space and matrix sparsification , and show that they are equivalent. We then proceed to seek algorithms for these problems: we prove the hardness of approximation of these problems, and also give a powerful tool to extend algorithms and heuristics for sparse approximation theory to these problems.

Description: We introduce Planar Disjoint Paths Completion , a completion counterpart of the Disjoint Paths problem, and study its parameterized complexity. The problem can be stated as follows: given a, not necessarily connected, plane graph G ,  k pairs of terminals, and a face F of G ,  find a minimum-size set of edges, if one exists, to be added inside F so that the embedding remains planar and the pairs become connected by k disjoint paths in the augmented network. Our results are twofold: first, we give an upper bound on the number of necessary additional edges when a solution exists. This bound is a function of k , independent of the size of G . Second, we show that the problem is fixed-parameter tractable, in particular, it can be solved in time \(f(k)\cdot n^{2}\) .

Description: Background: According to the World Health Organization 130–150 million (according to WHO) of people globally are chronically infected with hepatitis C virus. The virus is responsible for chronic hepatitis that ultimately may cause liver cirrhosis and death. The disease is progressive, however antiviral treatment may slow down or stop its development. Therefore, it is important to estimate the severity of liver fibrosis for diagnostic, therapeutic and prognostic purposes.Liver biopsy provides a high accuracy diagnosis, however it is painful and invasive procedure. Recently, we witness an outburst of non-invasive tests (biological and physical ones) aiming to define severity of liver fibrosis, but commonly used FibroTest®, according to an independent research, in some cases may have accuracy lower than 50 %. In this paper a data mining and classification technique is proposed to determine the stage of liver fibrosis using easily accessible laboratory data. Methods: Research was carried out on archival records of routine laboratory blood tests (morphology, coagulation, biochemistry, protein electrophoresis) and histopathology records of liver biopsy as a reference value. As a result, the granular model was proposed, that contains a series of intervals representing influence of separate blood attributes on liver fibrosis stage. The model determines final diagnosis for a patient using aggregation method and voting procedure. The proposed solution is robust to missing or corrupted data. Results: The results were obtained on data from 290 patients with hepatitis C virus collected over 6 years. The model has been validated using training and test data. The overall accuracy of the solution is equal to 67.9 %. The intermediate liver fibrosis stages are hard to distinguish, due to effectiveness of biopsy itself. Additionally, the method was verified against dataset obtained from 365 patients with liver disease of various etiologies. The model proved to be robust to new data. What is worth mentioning, the error rate in misclassification of the first stage and the last stage is below 6.5 % for all analyzed datasets. Conclusions: The proposed system supports the physician and defines the stage of liver fibrosis in chronic hepatitis C. The biggest advantage of the solution is a human-centric approach using intervals, which can be verified by a specialist, before giving the final decision. Moreover, it is robust to missing data. The system can be used as a powerful support tool for diagnosis in real treatment.

Description: This study proposes a quantitative measurement of split of the second heart sound (S2) based on nonstationary signal decomposition to deal with overlaps and energy modeling of the subcomponents of S2. The second heart sound includes aortic (A2) and pulmonic (P2) closure sounds. However, the split detection is obscured due to A2-P2 overlap and low energy of P2. To identify such split, HVD method is used to decompose the S2 into a number of components while preserving the phase information. Further, A2s and P2s are localized using smoothed pseudo Wigner-Ville distribution followed by reassignment method. Finally, the split iscalculated by taking the differences between the means of time indices of A2s and P2s. Experiments on total 33 clips of S2 signals are performed for evaluation of the method. The mean ± standard deviation of the split is 34.7 ± 4.6 ms. The method measures the splitefficiently, even when A2-P2 overlap is ≤ 20 ms and the normalized peak temporal ratio of P2 to A2 is low (≥ 0.22). This proposed method thus, demonstrates its robustness by defining split detectability (SDT), the split detection aptness through detecting P2s, by measuring upto 96 percent. Such findings reveal the effectiveness of the method as competent against the other baselines, especially for A2-P2 overlaps and low energy P2.

Description: Post-acquisition denoising of magnetic resonance (MR) images is an important step to improve any quantitative measurement of the acquired data. In this paper, assuming a Rician noise model, a new filtering method based on the linear minimum mean square error (LMMSE) estimation is introduced, which employs the self-similarity property of the MR data to restore the noise-less signal. This method takes into account the structural characteristics of images and the Bayesian mean square error (Bmse) of the estimator to address the denoising problem. In general, a twofold data processing approach is developed; first, the noisy MR data is processed using a patch-based L 2 -norm similarity measure to provide the primary set of samples required for the estimation process. Afterwards, the Bmse of the estimator is derived as the optimization function to analyze the pre-selected samples and minimize the error between the estimated and the underlying signal. Compared to the LMMSE method and also its recently proposed SNR-adapted realization (SNLMMSE), the optimized way of choosing the samples together with the automatic adjustment of the filtering parameters lead to a more robust estimation performance with our approach. Experimental results show the competitive performance of the proposed method in comparison with related state-of-the-art methods.

Description: Large-scale ad hoc analytics of genomic data is popular using the R-programming language supported by over 700 software packages provided by Bioconductor. More recently, analytical jobs are benefitting from on-demand computing and storage, their scalability and their low maintenance cost, all of which are offered by the cloud. While biologists and bioinformaticists can take an analytical job and execute it on their personal workstations, it remains challenging to seamlessly execute the job on the cloud infrastructure without extensive knowledge of the cloud dashboard. How analytical jobs can not only with minimum effort be executed on the cloud, but also how both the resources and data required by the job can be managed is explored in this paper. An open-source light-weight framework for executing R-scripts using Bioconductor packages, referred to as ‘RBioCloud’, is designed and developed. RBioCloud offers a set of simple command-line tools for managing the cloud resources, the data and the execution of the job. Three biological test cases validate the feasibility of RBioCloud. The framework is available from http://www.rbiocloud.com .

Description: Of major interest to translational genomics is the intervention in gene regulatory networks (GRNs) to affect cell behavior; in particular, to alter pathological phenotypes. Owing to the complexity of GRNs, accurate network inference is practically challenging and GRN models often contain considerable amounts of uncertainty. Considering the cost and time required for conducting biological experiments, it is desirable to have a systematic method for prioritizing potential experiments so that an experiment can be chosen to optimally reduce network uncertainty. Moreover, from a translational perspective it is crucial that GRN uncertainty be quantified and reduced in a manner that pertains to the operational cost that it induces, such as the cost of network intervention. In this work, we utilize the concept of mean objective cost of uncertainty (MOCU) to propose a novel framework for optimal experimental design. In the proposed framework, potential experiments are prioritized based on the MOCU expected to remain after conducting the experiment. Based on this prioritization, one can select an optimal experiment with the largest potential to reduce the pertinent uncertainty present in the current network model. We demonstrate the effectiveness of the proposed method via extensive simulations based on synthetic and real gene regulatory networks.

Description: A novel approach to Contact Map Overlap (CMO) problem is proposed using the two dimensional clusters present in the contact maps. Each protein is represented as a set of the non-trivial clusters of contacts extracted from its contact map. The approach involves finding matching regions between the two contact maps using approximate 2D-pattern matching algorithm and dynamic programming technique. These matched pairs of small contact maps are submitted in parallel to a fast heuristic CMO algorithm. The approach facilitates parallelization at this level since all the pairs of contact maps can be submitted to the algorithm in parallel. Then, a merge algorithm is used in order to obtain the overall alignment. As a proof of concept, MSVNS, a heuristic CMO algorithm is used for global as well as local alignment. The divide and conquer approach is evaluated for two benchmark data sets that of Skolnick and Ding et al. It is interesting to note that along with achieving saving of time, better overlap is also obtained for certain protein folds.

Description: Canalizing genes possess broad regulatory power over a wide swath of regulatory processes. On the other hand, it has been hypothesized that the phenomenon of intrinsically multivariate prediction (IMP) is associated with canalization. However, applications have relied on user-selectable thresholds on the IMP score to decide on the presence of IMP. A methodology is developed here that avoids arbitrary thresholds, by providing a statistical test for the IMP score. In addition, the proposed procedure allows the incorporation of prior knowledge if available, which can alleviate the problem of loss of power due to small sample sizes. The issue of multiplicity of tests is addressed by family-wise error rate (FWER) and false discovery rate (FDR) controlling approaches. The proposed methodology is demonstrated by experiments using synthetic and real gene-expression data from studies on melanoma and ionizing radiation (IR) responsive genes. The results with the real data identified DUSP1 and p53, two well-known canalizing genes associated with melanoma and IR response, respectively, as the genes with a clear majority of IMP predictor pairs. This validates the potential of the proposed methodology as a tool for discovery of canalizing genes from binary gene-expression data. The procedure is made available through an R package.

Description: Background: Health decision-making requires evidence from high-quality data. As one example, the Discharge Abstract Database (DAD) compiles data from the majority of Canadian hospitals to form one of the most comprehensive and highly regarded administrative health databases available for health research, internationally. However, despite the success of this and other administrative health data resources, little is known about their history or the factors that have led to their success. The purpose of this paper is to provide an historical overview of Canadian administrative health data for health research to contribute to the institutional memory of this field. Methods: We conducted a qualitative content analysis of approximately 20 key sources to construct an historical narrative of administrative health data in Canada. Specifically, we searched for content related to key events, individuals, challenges, and successes in this field over time. Results: In Canada, administrative health data for health research has developed in tangent with provincial research centres. Interestingly, the lessons learned from this history align with the original recommendations of the 1964 Royal Commission on Health Services: (1) standardization, and (2) centralization of data resources, that is (3) facilitated through governmental financial support. Conclusions: The overview history provided here illustrates the need for longstanding partnerships between government and academia, for classification, terminology and standardization are time-consuming and ever-evolving processes. This paper will be of interest to those who work with administrative health data, and also for countries that are looking to build or improve upon their use of administrative health data for decision-making.

Description: We prove that in a graph with n vertices, induced chordal and interval subgraphs with the maximum number of vertices can be found in time \(\mathcal {O}(2^{\lambda n})\) for some \(\lambda 〈1\) . These are the first algorithms breaking the trivial \(2^n n^{\mathcal {O}(1)}\) bound of the brute-force search for these problems.

Description: We investigate the effect of limiting the number of reserve prices on the revenue in a probabilistic single item auction. In the model considered, bidders compete for an impression drawn from a known distribution of possible types. The auction mechanism sets up to \(\ell \) reserve prices, and each impression type is assigned the highest reserve price lower than the valuation of some bidder for it. The bidder proposing the highest bid for an arriving impression gets it provided his bid is at least the corresponding reserve price, and pays the maximum between the reserve price and the second highest bid. Since the number of impression types may be huge, we consider the revenue \(R_{\ell }\) that can be ensured using only \(\ell \) reserve prices. Our main results are tight lower bounds on \(R_{\ell }\) for the cases where the impressions are drawn from the uniform or a general probability distribution.

Description: Background: There is general consensus that appropriate development and use of information and communication technologies (ICT) are crucial in the delivery of effective primary care (PC). Several countries are defining policies to support and promote a structural change of the health care system through the introduction of ICT. This study analyses the state of development of basic ICT in PC systems of 31 European countries with the aim to describe the extent of, and main purposes for, computer use by General Practitioners (GPs) across Europe. Additionally, trends over time have been analysed. Methods: Descriptive statistical analysis was performed on data from the QUALICOPC (Quality and Costs of Primary Care in Europe) survey, to describe the geographic differences in the general use of computer, and in specific computerized clinical functions for different health-related purposes such as prescribing, medication checking, generating health records and research for medical information on the Internet. Results: While all the countries have achieved a near-universal adoption of a computer in their primary care practices, with only a few countries near or under the boundary of 90 %, the computerisation of primary care clinical functions presents a wide variability of adoption within and among countries and, in several cases (such as in the southern and central-eastern Europe), a large room for improvement. Conclusions: At European level, more efforts could be done to support southern and central-eastern Europe in closing the gap in adoption and use of ICT in PC. In particular, more attention seems to be need on the current usages of the computer in PC, by focusing policies and actions on the improvement of the appropriate usages that can impact on quality and costs of PC and can facilitate an interconnected health care system. However, policies and investments seem necessary but not sufficient to achieve these goals. Organizational, behavioural and also networking aspects should be taken in consideration.

Description: Background: Bangladesh is facing serious shortage of trained health professionals. In the pluralistic healthcare system of Bangladesh, formal health care providers constitute only 5 % of the total workforce; the rest are informal health care providers. Information Communication Technologies (ICTs) are increasingly seen as a powerful tool for linking the community with formal healthcare providers. Our study assesses an intervention that linked village doctors (a cadre of informal health care providers practising modern medicine) to formal doctors through call centres from the perspective of the village doctors who participated in the intervention. Methods: The study was conducted in Chakaria, a remote rural area in south-eastern Bangladesh during April–May 2013. Twelve village doctors were selected purposively from a pool of 55 village doctors who participated in the mobile health (mHealth) intervention. In depth interviews were conducted to collect data. The data were manually analysed using themes that emerged.ResultThe village doctors talked about both business benefits (access to formal doctors, getting support for decision making, and being entitled to call trained doctors) and personal benefits (both financial and non-financial). Some of the major barriers mentioned were technical problems related to accessing the call centre, charging consultation fees, and unfamiliarity with the call centre physicians. Conclusion: Village doctors saw many benefits to having a business relationship with the trained doctors that the mHealth intervention provided. mHealth through call centres has the potential to ensure consultation services to populations through existing informal healthcare providers in settings with a shortage of qualified healthcare providers.

Description: Background: Choosing the most appropriate family physician (FP) for the individual, plays a fundamental role in primary care. The aim of this study is to determine the selection criteria for the patients in choosing their family doctors and priority ranking of these criteria by using the multi-criteria decision-making method of the Analytic Hierarchy Process (AHP) model. Methods: The study was planned and conducted in two phases. In the first phase, factors affecting the patients’ decisions were revealed with a qualitative research. In the next phase, the priorities of FP selection criteria were determined by using AHP model. Criteria were compared in pairs. 96 patient were asked to fill the information forms which contains comparison scores in the Family Health Centres. Results: According to the analysis of focus group discussions FP selection criteria were congregated in to five groups: Individual Characteristics, Patient-Doctor relationship, Professional characteristics, the Setting, and Ethical Characteristics.For each of the 96 participants, comparison matrixes were formed based on the scores of their information forms. Of these, models of only 5 (5.2 %) of the participants were consistent, in other words, they have been able to score consistent ranking. The consistency ratios (CR) were found to be smaller than 0.10. Therefore the comparison matrix of this new model, which was formed based on the medians of scores only given by these 5 participants, was consistent (CR = 0.06 

Description: The Regression Network plugin for Cytoscape ( RegNetC ) implements the RegNet algorithm for the inference of transcriptional association network from gene expression profiles. This algorithm is a model tree-based method to detect the relationship between each gene and the remaining genes simultaneously instead of analyzing individually each pair of genes as correlation-based methods do. Model trees are a very useful technique to estimate the gene expression value by regression models and favours localized similarities over more global similarity, which is one of the major drawbacks of correlation-based methods. Here, we present an integrated software suite, named RegNetC , as a Cytoscape plugin that can operate on its own as well. RegNetC facilitates, according to user-defined parameters, the resulted transcriptional gene association network in .sif format for visualization, analysis and interoperates with other Cytoscape plugins, which can be exported for publication figures. In addition to the network, the RegNetC plugin also provides the quantitative relationships between genes expression values of those genes involved in the inferred network, i.e., those defined by the regression models.

Description: We introduce a new method for normalization of data acquired by liquid chromatography coupled with mass spectrometry (LC-MS) in label-free differential expression analysis. Normalization of LC-MS data is desired prior to subsequent statistical analysis to adjust variabilities in ion intensities that are not caused by biological differences but experimental bias. There are different sources of bias including variabilities during sample collection and sample storage, poor experimental design, noise, etc. In addition, instrument variability in experiments involving a large number of LC-MS runs leads to a significant drift in intensity measurements. Although various methods have been proposed for normalization of LC-MS data, there is no universally applicable approach. In this paper, we propose a Bayesian normalization model (BNM) that utilizes scan-level information from LC-MS data. Specifically, the proposed method uses peak shapes to model the scan-level data acquired from extracted ion chromatograms (EIC) with parameters considered as a linear mixed effects model. We extended the model into BNM with drift (BNMD) to compensate for the variability in intensity measurements due to long LC-MS runs. We evaluated the performance of our method using synthetic and experimental data. In comparison with several existing methods, the proposed BNM and BNMD yielded significant improvement.

Description: Performing clustering analysis is one of the important research topics in cancer discovery using gene expression profiles, which is crucial in facilitating the successful diagnosis and treatment of cancer. While there are quite a number of research works which perform tumor clustering, few of them considers how to incorporate fuzzy theory together with an optimization process into a consensus clustering framework to improve the performance of clustering analysis. In this paper, we first propose a random double clustering based cluster ensemble framework (RDCCE) to perform tumor clustering based on gene expression data. Specifically, RDCCE generates a set of representative features using a randomly selected clustering algorithm in the ensemble, and then assigns samples to their corresponding clusters based on the grouping results. In addition, we also introduce the random double clustering based fuzzy cluster ensemble framework (RDCFCE), which is designed to improve the performance of RDCCE by integrating the newly proposed fuzzy extension model into the ensemble framework. RDCFCE adopts the normalized cut algorithm as the consensus function to summarize the fuzzy matrices generated by the fuzzy extension models, partition the consensus matrix, and obtain the final result. Finally, adaptive RDCFCE (A-RDCFCE) is proposed to optimize RDCFCE and improve the performance of RDCFCE further by adopting a self-evolutionary process (SEPP) for the parameter set. Experiments on real cancer gene expression profiles indicate that RDCFCE and A-RDCFCE works well on these data sets, and outperform most of the state-of-the-art tumor clustering algorithms.

Description: Named-entity recognition (NER) plays an important role in the development of biomedical databases. However, the existing NER tools produce multifarious named-entities which may result in both curatable and non-curatable markers. To facilitate biocuration with a straightforward approach, classifying curatable named-entities is helpful with regard to accelerating the biocuration workflow. Co-occurrence Interaction Nexus with Named-entity Recognition (CoINNER) is a web-based tool that allows users to identify genes, chemicals, diseases, and action term mentions in the Comparative Toxicogenomic Database (CTD). To further discover interactions, CoINNER uses multiple advanced algorithms to recognize the mentions in the BioCreative IV CTD Track. CoINNER is developed based on a prototype system that annotated gene, chemical, and disease mentions in PubMed abstracts at BioCreative 2012 Track I (literature triage). We extended our previous system in developing CoINNER. The pre-tagging results of CoINNER were developed based on the state-of-the-art named entity recognition tools in BioCreative III. Next, a method based on conditional random fields (CRFs) is proposed to predict chemical and disease mentions in the articles. Finally, action term mentions were collected by latent Dirichlet allocation (LDA). At the BioCreative IV CTD Track, the best F-measures reached for gene/protein, chemical/drug and disease NER were 54 percent while CoINNER achieved a 61.5 percent F-measure. System URL: http://ikmbio.csie.ncku.edu.tw/coinner/introduction.htm.

Description: Next-generation short-read sequencing is widely utilized in genomic studies. Biological applications require an alignment step to map sequencing reads to the reference genome, before acquiring expected genomic information. This requirement makes alignment accuracy a key factor for effective biological interpretation. Normally, when accounting for measurement errors and single nucleotide polymorphisms, short read mappings with a few mismatches are generally considered acceptable. However, to further improve the efficiency of short-read sequencing alignment, we propose a method to retrieve additional reliably aligned reads (reads with more than a pre-defined number of mismatches), using a Bayesian-based approach. In this method, we first retrieve the sequence context around the mismatched nucleotides within the already aligned reads; these loci contain the genomic features where sequencing errors occur. Then, using the derived pattern, we evaluate the remaining (typically discarded) reads with more than the allowed number of mismatches, and calculate a score that represents the probability that a specific alignment is correct. This strategy allows the extraction of more reliably aligned reads, therefore improving alignment sensitivity. Implementation: The source code of our tool, ResSeq, can be downloaded from: https://github.com/hrbeubiocenter/Resseq.

Description: In genome assembly graphs, motifs such as tips, bubbles, and cross links are studied in order to find sequencing errors and to understand the nature of the genome. Superbubble, a complex generalization of bubbles, was recently proposed as an important subgraph class for analyzing assembly graphs. At present, a quadratic time algorithm is known. This paper gives an -time algorithm to solve this problem for a graph with $m$ edges.

Description: The papers in this special section focus on software and databases that are central in bioinformatics and computational biology.. These programs are playing more and more important roles in biology and medical research. These papers cover a broad range of topics, including computational genomics and transcriptomics, analysis of biological networks and interactions, drug design, biomedical signal/image analysis, biomedical text mining and ontologies, biological data mining, visualization and integration, and high performance computing application in bioinformatics.

Description: In the computational biology community, machine learning algorithms are key instruments for many applications, including the prediction of gene-functions based upon the available biomolecular annotations. Additionally, they may also be employed to compute similarity between genes or proteins. Here, we describe and discuss a software suite we developed to implement and make publicly available some of such prediction methods and a computational technique based upon Latent Semantic Indexing (LSI), which leverages both inferred and available annotations to search for semantically similar genes. The suite consists of three components. BioAnnotationPredictor is a computational software module to predict new gene-functions based upon Singular Value Decomposition of available annotations. SimilBio is a Web module that leverages annotations available or predicted by BioAnnotationPredictor to discover similarities between genes via LSI. The suite includes also SemSim , a new Web service built upon these modules to allow accessing them programmatically. We integrated SemSim in the Bio Search Computing framework (http://www.bioinformatics.deib.polimi.it/bio-seco/seco/), where users can exploit the Search Computing technology to run multi-topic complex queries on multiple integrated Web services. Accordingly, researchers may obtain ranked answers involving the computation of the functional similarity between genes in support of biomedical knowledge discovery.

Description: Identification of cancer subtypes plays an important role in revealing useful insights into disease pathogenesis and advancing personalized therapy. The recent development of high-throughput sequencing technologies has enabled the rapid collection of multi-platform genomic data (e.g., gene expression, miRNA expression, and DNA methylation) for the same set of tumor samples. Although numerous integrative clustering approaches have been developed to analyze cancer data, few of them are particularly designed to exploit both deep intrinsic statistical properties of each input modality and complex cross-modality correlations among multi-platform input data. In this paper, we propose a new machine learning model, called multimodal deep belief network (DBN), to cluster cancer patients from multi-platform observation data. In our integrative clustering framework, relationships among inherent features of each single modality are first encoded into multiple layers of hidden variables, and then a joint latent model is employed to fuse common features derived from multiple input modalities. A practical learning algorithm, called contrastive divergence (CD), is applied to infer the parameters of our multimodal DBN model in an unsupervised manner. Tests on two available cancer datasets show that our integrative data analysis approach can effectively extract a unified representation of latent features to capture both intra- and cross-modality correlations, and identify meaningful disease subtypes from multi-platform cancer data. In addition, our approach can identify key genes and miRNAs that may play distinct roles in the pathogenesis of different cancer subtypes. Among those key miRNAs, we found that the expression level of miR-29a is highly correlated with survival time in ovarian cancer patients. These results indicate that our multimodal DBN based data analysis approach may have practical applications in cancer pathogenesis studies and provide useful guidelines for personali- ed cancer therapy.

Description: The new dual-pivot Quicksort by Vladimir Yaroslavskiy—used in Oracle’s Java runtime library since version 7—features intriguing asymmetries. They make a basic variant of this algorithm use less comparisons than classic single-pivot Quicksort. In this paper, we extend the analysis to the case where the two pivots are chosen as fixed order statistics of a random sample. Surprisingly, dual-pivot Quicksort then needs more comparisons than a corresponding version of classic Quicksort, so it is clear that counting comparisons is not sufficient to explain the running time advantages observed for Yaroslavskiy’s algorithm in practice. Consequently, we take a more holistic approach and give also the precise leading term of the average number of swaps, the number of executed Java Bytecode instructions and the number of scanned elements, a new simple cost measure that approximates I/O costs in the memory hierarchy. We determine optimal order statistics for each of the cost measures. It turns out that the asymmetries in Yaroslavskiy’s algorithm render pivots with a systematic skew more efficient than the symmetric choice. Moreover, we finally have a convincing explanation for the success of Yaroslavskiy’s algorithm in practice: compared with corresponding versions of classic single-pivot Quicksort, dual-pivot Quicksort needs significantly less I/Os, both with and without pivot sampling.

Description: In this paper, we consider the Unsplittable (hard) Capacitated Facility Location Problem (UCFLP) with uniform capacities and present new approximation algorithms for it. This problem is a generalization of the classical facility location problem where each facility can serve at most u units of demand and each client must be served by exactly one facility. This problem is motivated by its applications in many practical problems including supply chain problems of indivisible goods (Verter in Foundations of location analysis, chapter 2. International series in operations research and management science. Springer, Berlin, 2011 ) and the assignment problem in the content distribution networks (Bateni and Hajiaghayi in Proceedings of the nineteenth annual ACM-SIAM symposium on discrete algorithms, pp 805–814, 2009 ). While there are several approximation algorithms for the soft capacitated version of this problem (in which one can open multiple copies of each facility) or the splittable version (in which the demand of each client can be divided to be served by multiple open facilities), there are very few results for the UCFLP. It is known that it is NP-hard to approximate this problem within any factor without violating the capacities. So we consider bicriteria \((\alpha ,\beta )\) -approximations where the algorithm returns a solution whose cost is within factor \(\alpha \) of the optimum and violates the capacity constraints within factor \(\beta \) . Shmoys et al. (Proceedings of the twenty-ninth annual ACM symposium on theory of computing, pp 265–274, 1997 ) were the first to consider this problem and gave a (9, 4)-approximation. Later results imply ( O (1), 2)-approximations, however, no constant factor approximation is known with capacity violation of less than 2. We present a framework for designing bicriteria approximation algorithms for this problem and show two new approximation algorithms with factors (9, 3 / 2) and (29.315, 4 / 3). These are the first algorithms with constant approximation in which the violation of capacities is below 2. The heart of our algorithm is a reduction from the UCFLP to a restricted version of the problem. One feature of this reduction is that any \((O(1),1+{\epsilon })\) -approximation for the restricted version implies an \((O(1),1+{\epsilon })\) -approximation for the UCFLP and we believe our techniques might be useful towards finding such approximations or perhaps \((f({\epsilon }),1+{\epsilon })\) -approximation for the UCFLP for some function f . In addition, we present a quasi-polynomial time \((1+\epsilon ,1+\epsilon )\) -approximation for the (uniform) UCFLP in Euclidean metrics, for any constant \({\epsilon }〉0\) .

Description: The papers in this special issue contain extended versions of works that were originally presented at the Brazilian Symposium on Bioinformatics 2013 (BSB 2013), held in Recife, Brazil, November 3-6, 2013.

Description: Computational methods for predicting protein-protein interactions are important tools that can complement high-throughput technologies and guide biologists in designing new laboratory experiments. The proteins and the interactions between them can be described by a network which is characterized by several topological properties. Information about proteins and interactions between them, in combination with knowledge about topological properties of the network, can be used for developing computational methods that can accurately predict unknown protein-protein interactions. This paper presents a supervised learning framework based on Bayesian inference for combining two types of information: i) network topology information, and ii) information related to proteins and the interactions between them. The motivation of our model is that by combining these two types of information one can achieve a better accuracy in predicting protein-protein interactions, than by using models constructed from these two types of information independently.

Description: We develop a theory of algebraic operations over linear and context-free grammars that makes it possible to combine simple “atomic” grammars operating on single sequences into complex, multi-dimensional grammars. We demonstrate the utility of this framework by constructing the search spaces of complex alignment problems on multiple input sequences explicitly as algebraic expressions of very simple one-dimensional grammars. In particular, we provide a fully worked frameshift-aware, semiglobal DNA-protein alignment algorithm whose grammar is composed of products of small, atomic grammars. The compiler accompanying our theory makes it easy to experiment with the combination of multiple grammars and different operations. Composite grammars can be written out in $ {rm L}^AT_{E}X$ for documentation and as a guide to implementation of dynamic programming algorithms. An embedding in Haskell as a domain-specific language makes the theory directly accessible to writing and using grammar products without the detour of an external compiler. Software and supplemental files available here: http://www.bioinf.uni-leipzig.de/Software/gramprod/

Description: Recent advancements in genomics and proteomics provide a solid foundation for understanding the pathogenesis of diabetes. Proteomics of diabetes associated pathways help to identify the most potent target for the management of diabetes. The relevant datasets are scattered in various prominent sources which takes much time to select the therapeutic target for the clinical management of diabetes. However, additional information about target proteins is needed for validation. This lacuna may be resolved by linking diabetes associated genes, pathways and proteins and it will provide a strong base for the treatment and planning management strategies of diabetes. Thus, a web source “Diabetes Associated Proteins Database (DAPD)” has been developed to link the diabetes associated genes, pathways and proteins using PHP, MySQL. The current version of DAPD has been built with proteins associated with different types of diabetes. In addition, DAPD has been linked to external sources to gain the access to more participatory proteins and their pathway network. DAPD will reduce the time and it is expected to pave the way for the discovery of novel anti-diabetic leads using computational drug designing for diabetes management. DAPD is open accessed via following url www.mkarthikeyan.bioinfoau.org/dapd.

Description: Determining the glycan topology automatically from mass spectra represents a great challenge. Existing methods fall into approximate and exact ones. The former including greedy and heuristic ones can reduce the computational complexity, but suffer from information lost in the procedure of glycan interpretation. The latter including dynamic programming and exhaustive enumeration are much slower than the former. In the past years, nearly all emerging methods adopted a tree structure to represent a glycan. They share such problems as repetitive peak counting in reconstructing a candidate structure. Besides, tree-based glycan representation methods often have to give different computational formulas for binary and ternary glycans. We propose a new directed acyclic graph structure for glycan representation. Based on it, this work develops a de novo algorithm to accurately reconstruct the tree structure iteratively from mass spectra with logical constraints and some known biosynthesis rules, by a single computational formula. The experiments on multiple complex glycans extracted from human serum show that the proposed algorithm can achieve higher accuracy to determine a glycan topology than prior methods without increasing computational burden.

Description: A crucial step in understanding the architecture of cells and tissues from microscopy images, and consequently explain important biological events such as wound healing and cancer metastases, is the complete extraction and enumeration of individual filaments from the cellular cytoskeletal network. Current efforts at quantitative estimation of filament length distribution, architecture and orientation from microscopy images are predominantly limited to visual estimation and indirect experimental inference. Here we demonstrate the application of a new algorithm to reliably estimate centerlines of biological filament bundles and extract individual filaments from the centerlines by systematically disambiguating filament intersections. We utilize a filament enhancement step followed by reverse diffusion based filament localization and an integer programming based set combination to systematically extract accurate filaments automatically from microscopy images. Experiments on simulated and real confocal microscope images of flat cells (2D images) show efficacy of the new method.

Description: The Local/Global Alignment (Zemla, 2003), or LGA, is a popular method for the comparison of protein structures. One of the two components of LGA requires us to compute the longest common contiguous segments between two protein structures. That is, given two structures $A=(a_1, ldots , a_n)$ and $B=(b_1, ldots , b_n)$ where $a_k$ , $b_kin mathbb {R}^3$ , we are to find, among all the segments $f=(a_i,ldots ,a_j)$ and $g=(b_i,ldots ,b_j)$ that fulfill a certain criterion regarding their similarity, those of the maximum length. We consider the following criteria: (1) the root mean squared deviation (RMSD) between $f$ and $g$ is to be within a given $tin mathbb {R}$ ; (2) $f$ and $g$ can be superposed such that for each $k$ , $ile kle j$ , $Vert a_k-b_kVert le t$ for a given $tin mathbb {R}$ . We give an algorithm of $O(n;log; n+n{{boldsymbol l}})$ time complexity when the first requirement applies, where ${{boldsymbol l}}$ is the maximum length of the segments fulfilling the criterion. We show an FPTAS which, for any

Description: Noise can induce various dynamical behaviors in nonlinear systems. White noise perturbed systems have been extensively investigated during the last decades. In gene networks, experimentally observed extrinsic noise is colored. As an attempt, we investigate the genetic toggle switch systems perturbed by colored extrinsic noise and with kinetic parameters. Compared with white noise perturbed systems, we show there also exists optimal colored noise strength to induce the best stochastic switch behaviors in the single toggle switch, and the best synchronized switching in the networked systems, which demonstrate that noise-induced optimal switch behaviors are widely in existence. Moreover, under a wide range of system parameter regions, we find there exist wider ranges of white and colored noises strengths to induce good switch and synchronization behaviors, respectively; therefore, white noise is beneficial for switch and colored noise is beneficial for population synchronization. Our observations are very robust to extrinsic stimulus strength, cell density, and diffusion rate. Finally, based on the Waddington’s epigenetic landscape and the Wiener-Khintchine theorem, physical mechanisms underlying the observations are interpreted. Our investigations can provide guidelines for experimental design, and have potential clinical implications in gene therapy and synthetic biology.

Description: Revealing the underlying evolutionary mechanism plays an important role in understanding protein interaction networks in the cell. While many evolutionary models have been proposed, the problem about applying these models to real network data, especially for differentiating which model can better describe evolutionary process for the observed network remains a challenge. The traditional way is to use a model with presumed parameters to generate a network, and then evaluate the fitness by summary statistics, which however cannot capture the complete network structures information and estimate parameter distribution. In this work, we developed a novel method based on Approximate Bayesian Computation and modified Differential Evolution algorithm (ABC-DEP) that is capable of conducting model selection and parameter estimation simultaneously and detecting the underlying evolutionary mechanisms for PPI networks more accurately. We tested our method for its power in differentiating models and estimating parameters on simulated data and found significant improvement in performance benchmark, as compared with a previous method. We further applied our method to real data of protein interaction networks in human and yeast. Our results show duplication attachment model as the predominant evolutionary mechanism for human PPI networks and Scale-Free model as the predominant mechanism for yeast PPI networks.

Description: Single nucleotide polymorphisms, a dominant type of genetic variants, have been used successfully to identify defective genes causing human single gene diseases. However, most common human diseases are complex diseases and caused by gene-gene and gene-environment interactions. Many SNP-SNP interaction analysis methods have been introduced but they are not powerful enough to discover interactions more than three SNPs. The paper proposes a novel method that analyzes all SNPs simultaneously. Different from existing methods, the method regards an individual’s genotype data on a list of SNPs as a point with a unit of energy in a multi-dimensional space, and tries to find a new coordinate system where the energy distribution difference between cases and controls reaches the maximum. The method will find different multiple SNPs combinatorial patterns between cases and controls based on the new coordinate system. The experiment on simulated data shows that the method is efficient. The tests on the real data of age-related macular degeneration (AMD) disease show that it can find out more significant multi-SNP combinatorial patterns than existing methods.

Description: Disulfide connectivity is an important protein structural characteristic. Accurately predicting disulfide connectivity solely from protein sequence helps to improve the intrinsic understanding of protein structure and function, especially in the post-genome era where large volume of sequenced proteins without being functional annotated is quickly accumulated. In this study, a new feature extracted from the predicted protein 3D structural information is proposed and integrated with traditional features to form discriminative features. Based on the extracted features, a random forest regression model is performed to predict protein disulfide connectivity. We compare the proposed method with popular existing predictors by performing both cross-validation and independent validation tests on benchmark datasets. The experimental results demonstrate the superiority of the proposed method over existing predictors. We believe the superiority of the proposed method benefits from both the good discriminative capability of the newly developed features and the powerful modelling capability of the random forest. The web server implementation, called TargetDisulfide, and the benchmark datasets are freely available at: http://csbio.njust.edu.cn/bioinf/TargetDisulfide for academic use.

Description: Proteins are molecules that form the mass of living beings. These proteins exist in dissociated forms like amino-acids and carry out various biological functions, in fact, almost all body reactions occur with the participation of proteins. This is one of the reasons why the analysis of proteins has become a major issue in biology. In a more concrete way, the identification of conserved patterns in a set of related protein sequences can provide relevant biological information about these protein functions. In this paper, we present a novel algorithm based on teaching learning based optimization (TLBO) combined with a local search function specialized to predict common patterns in sets of protein sequences. This population-based evolutionary algorithm defines a group of individuals (solutions) that enhance their knowledge (quality) by means of different learning stages. Thus, if we correctly adapt it to the biological context of the mentioned problem, we can get an acceptable set of quality solutions. To evaluate the performance of the proposed technique, we have used six instances composed of different related protein sequences obtained from the PROSITE database. As we will see, the designed approach makes good predictions and improves the quality of the solutions found by other well-known biological tools.

Description: We introduce Supervised Variational Relevance Learning (Suvrel), a variational method to determine metric tensors to define distance based similarity in pattern classification, inspired in relevance learning. The variational method is applied to a cost function that penalizes large intraclass distances and favors small interclass distances. We find analytically the metric tensor that minimizes the cost function. Preprocessing the patterns by doing linear transformations using the metric tensor yields a dataset which can be more efficiently classified. We test our methods using publicly available datasets, for some standard classifiers. Among these datasets, two were tested by the MAQC-II project and, even without the use of further preprocessing, our results improve on their performance.

Description: Genes can participate in multiple biological processes at a time and thus their expression can be seen as a composition of the contributions from the active processes. Biclustering under a plaid assumption allows the modeling of interactions between transcriptional modules or biclusters (subsets of genes with coherence across subsets of conditions) by assuming an additive composition of contributions in their overlapping areas. Despite the biological interest of plaid models, few biclustering algorithms consider plaid effects and, when they do, they place restrictions on the allowed types and structures of biclusters, and suffer from robustness problems by seizing exact additive matchings. We propose BiP (Biclustering using Plaid models), a biclustering algorithm with relaxations to allow expression levels to change in overlapping areas according to biologically meaningful assumptions (weighted and noise-tolerant composition of contributions). BiP can be used over existing biclustering solutions (seizing their benefits) as it is able to recover excluded areas due to unaccounted plaid effects and detect noisy areas non-explained by a plaid assumption, thus producing an explanatory model of overlapping transcriptional activity. Experiments on synthetic data support BiP’s efficiency and effectiveness. The learned models from expression data unravel meaningful and non-trivial functional interactions between biological processes associated with putative regulatory modules.

Description: We propose a classifier system called iPFPi that predicts the functions of un-annotated proteins. iPFPi assigns an un-annotated protein $P$ the functions of GO annotation terms that are semantically similar to $P$ . An un-annotated protein $P$ and a GO annotation term $T$ are represented by their characteristics. The characteristics of $P$ are GO terms found within the abstracts of biomedical literature associated with $P$ . The characteristics of $T$ are GO terms found within the abstracts of biomedical literature associated with the proteins annotated with the function of $T$ . Let - F$ and $Fprime $ be the important (dominant) sets of characteristic terms representing $T$ and $P$ , respectively. iPFPi would annotate $P$ with the function of $T$ , if $F$ and $Fprime $ are semantically similar. We constructed a novel semantic similarity measure that takes into consideration several factors, such as the dominance degree of each characteristic term $t$ in set $F$

Description: Adverse drug reaction (ADR) is a common clinical problem, sometimes accompanying with high risk of mortality and morbidity. It is also one of the major factors that lead to failure in new drug development. Unfortunately, most of current experimental and computational methods are unable to evaluate clinical safety of drug candidates in early drug discovery stage due to the very limited knowledge of molecular mechanisms underlying ADRs. Therefore, in this study, we proposed a novel naïve Bayesian model for rapid assessment of clinical ADRs with frequency estimation. This model was constructed on a gene-ADR association network, which covered 611 US FDA approved drugs, 14,251 genes, and 1,254 distinct ADR terms. An average detection rate of 99.86 and 99.73 percent were achieved eventually in identification of known ADRs in internal test data set and external case analyses respectively. Moreover, a comparative analysis between the estimated frequencies of ADRs and their observed frequencies was undertaken. It is observed that these two frequencies have the similar distribution trend. These results suggest that the naïve Bayesian model based on gene-ADR association network can serve as an efficient and economic tool in rapid ADRs assessment.

Description: The papers in this special section were presented at the 13th International Workshop on Data Mining in Bioinformatics (BIOKDD???14) was organized in conjunction with the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining that was held on August 24, 2014 in New York, NY. It brought together international researchers in the interacting disciplines of data mining, systems biology, and bioinformatics at the Bloomberg Headquarters venue. The goal of this workshop is to encourage Knowledge Discovery and Data mining (KDD) researchers to take on the numerous challenges that Bioinformatics offers.

Description: The introduction of next-generation sequencing technologies has radically changed the way we view structural genetic events. Microhomology-mediated break-induced replication (MMBIR) is just one of the many mechanisms that can cause genomic destabilization that may lead to cancer. Although the mechanism for MMBIR remains unclear, it has been shown that MMBIR is typically associated with template-switching events. Currently, to our knowledge, there is no existing bioinformatics tool to detect these template-switching events. We have developed MMBIRFinder, a method that detects template-switching events associated with MMBIR from whole-genome sequenced data. MMBIRFinder uses a half-read alignment approach to identify potential regions of interest. Clustering of these potential regions helps narrow the search space to regions with strong evidence. Subsequent local alignments identify the template-switching events with single-nucleotide accuracy. Using simulated data, MMBIRFinder identified 83 percent of the MMBIR regions within a five nucleotide tolerance. Using real data, MMBIRFinder identified 16 MMBIR regions on a normal breast tissue data sample and 51 MMBIR regions on a triple-negative breast cancer tumor sample resulting in detection of 37 novel template-switching events. Finally, we identified template-switching events residing in the promoter region of seven genes that have been implicated in breast cancer. The program is freely available for download at https://github.com/msegar/MMBIRFinder.

Description: Compressing heterogeneous collections of trees is an open problem in computational phylogenetics. In a heterogeneous tree collection, each tree can contain a unique set of taxa. An ideal compression method would allow for the efficient archival of large tree collections and enable scientists to identify common evolutionary relationships over disparate analyses. In this paper, we extend TreeZip to compress heterogeneous collections of trees. TreeZip is the most efficient algorithm for compressing homogeneous tree collections. To the best of our knowledge, no other domain-based compression algorithm exists for large heterogeneous tree collections or enable their rapid analysis. Our experimental results indicate that TreeZip averages 89.03 percent (72.69 percent) space savings on unweighted (weighted) collections of trees when the level of heterogeneity in a collection is moderate. The organization of the TRZ file allows for efficient computations over heterogeneous data. For example, consensus trees can be computed in mere seconds. Lastly, combining the TreeZip compressed (TRZ) file with general-purpose compression yields average space savings of 97.34 percent (81.43 percent) on unweighted (weighted) collections of trees. Our results lead us to believe that TreeZip will prove invaluable in the efficient archival of tree collections, and enables scientists to develop novel methods for relating heterogeneous collections of trees.

Description: The papers in this special section were presented at the 2014 International Conference on Genome Informatics (GIW).

Description: Cluster analysis of biological networks is one of the most important approaches for identifying functional modules and predicting protein functions. Furthermore, visualization of clustering results is crucial to uncover the structure of biological networks. In this paper, ClusterViz, an APP of Cytoscape 3 for cluster analysis and visualization, has been developed. In order to reduce complexity and enable extendibility for ClusterViz, we designed the architecture of ClusterViz based on the framework of Open Services Gateway Initiative. According to the architecture, the implementation of ClusterViz is partitioned into three modules including interface of ClusterViz, clustering algorithms and visualization and export. ClusterViz fascinates the comparison of the results of different algorithms to do further related analysis. Three commonly used clustering algorithms, FAG-EC, EAGLE and MCODE, are included in the current version. Due to adopting the abstract interface of algorithms in module of the clustering algorithms, more clustering algorithms can be included for the future use. To illustrate usability of ClusterViz, we provided three examples with detailed steps from the important scientific articles, which show that our tool has helped several research teams do their research work on the mechanism of the biological networks.

Description: Structural domains are evolutionary and functional units of proteins and play a critical role in comparative and functional genomics. Computational assignment of domain function with high reliability is essential for understanding whole-protein functions. However, functional annotations are conventionally assigned onto full-length proteins rather than associating specific functions to the individual structural domains. In this article, we present Structural Domain Annotation (SDA), a novel computational approach to predict functions for SCOP structural domains. The SDA method integrates heterogeneous information sources, including structure alignment based protein-SCOP mapping features, InterPro2GO mapping information, PSSM Profiles, and sequence neighborhood features, with a Bayesian network. By large-scale annotating Gene Ontology terms to SCOP domains with SDA, we obtained a database of SCOP domain to Gene Ontology mappings, which contains $sim$ 162,000 out of the approximately 166,900 domains in SCOPe 2.03 ( $>$ 97 percent) and their predicted Gene Ontology functions. We have benchmarked SDA using a single-domain protein dataset and an independent dataset from different species. Comparative studies show that SDA significantly outperforms the existing function prediction methods for structural domains in terms of coverage and maximum F-measure.

Description: A major challenge in computational biology is to find simple representations of high-dimensional data that best reveal the underlying structure. In this work, we present an intuitive and easy-to-implement method based on ranked neighborhood comparisons that detects structure in unsupervised data. The method is based on ordering objects in terms of similarity and on the mutual overlap of nearest neighbors. This basic framework was originally introduced in the field of social network analysis to detect actor communities. We demonstrate that the same ideas can successfully be applied to biomedical data sets in order to reveal complex underlying structure. The algorithm is very efficient and works on distance data directly without requiring a vectorial embedding of data. Comprehensive experiments demonstrate the validity of this approach. Comparisons with state-of-the-art clustering methods show that the presented method outperforms hierarchical methods as well as density based clustering methods and model-based clustering. A further advantage of the method is that it simultaneously provides a visualization of the data. Especially in biomedical applications, the visualization of data can be used as a first pre-processing step when analyzing real world data sets to get an intuition of the underlying data structure. We apply this model to synthetic data as well as to various biomedical data sets which demonstrate the high quality and usefulness of the inferred structure.

Description: Proline residues are common source of kinetic complications during folding. The X-Pro peptide bond is the only peptide bond for which the stability of the cis and trans conformations is comparable. The cis-trans isomerization (CTI) of X-Pro peptide bonds is a widely recognized rate-limiting factor, which can not only induces additional slow phases in protein folding but also modifies the millisecond and sub-millisecond dynamics of the protein. An accurate computational prediction of proline CTI is of great importance for the understanding of protein folding, splicing, cell signaling, and transmembrane active transport in both the human body and animals. In our earlier work, we successfully developed a biophysically motivated proline CTI predictor utilizing a novel tree-based consensus model with a powerful metalearning technique and achieved 86.58 percent Q2 accuracy and 0.74 Mcc, which is a better result than the results (70-73 percent Q2 accuracies) reported in the literature on the well-referenced benchmark dataset. In this paper, we describe experiments with novel randomized subspace learning and bootstrap seeding techniques as an extension to our earlier work, the consensus models as well as entropy-based learning methods, to obtain better accuracy through a precise and robust learning scheme for proline CTI prediction.

Description: Efficient search algorithms for finding genomic-range overlaps are essential for various bioinformatics applications. A majority of fast algorithms for searching the overlaps between a query range (e.g., a genomic variant) and a set of N reference ranges (e.g., exons) has time complexity of O ( k + log N ), where k denotes a term related to the length and location of the reference ranges. Here, we present a simple but efficient algorithm that reduces k, based on the maximum reference range length. Specifically, for a given query range and the maximum reference range length, the proposed method divides the reference range set into three subsets: always , potentially , and never overlapping . Therefore, search effort can be reduced by excluding never overlapping subset. We demonstrate that the running time of the proposed algorithm is proportional to potentially overlapping subset size, that is proportional to the maximum reference range length if all the other conditions are the same. Moreover, an implementation of our algorithm was 13.8 to 30.0 percent faster than one of the fastest range search methods available when tested on various genomic-range data sets. The proposed algorithm has been incorporated into a disease-linked variant prioritization pipeline for WGS (http://gnome.tchlab.org) and its implementation is available at http://ml.ssu.ac.kr/gSearch.

Description: The identification of protein complexes in protein-protein interaction (PPI) networks is fundamental for understanding biological processes and cellular molecular mechanisms. Many graph computational algorithms have been proposed to identify protein complexes from PPI networks by detecting densely connected groups of proteins. These algorithms assess the density of subgraphs through evaluation of the sum of individual edges or nodes; thus, incomplete and inaccurate measures may miss meaningful biological protein complexes with functional significance. In this study, we propose a novel method for assessing the compactness of local subnetworks by measuring the number of three node cliques. The present method detects each optimal cluster by growing a seed and maximizing the compactness function. To demonstrate the efficacy of the new proposed method, we evaluate its performance using five PPI networks on three reference sets of yeast protein complexes with five different measurements and compare the performance of the proposed method with four state-of-the-art methods. The results show that the protein complexes generated by the proposed method are of better quality than those generated by four classic methods. Therefore, the new proposed method is effective and useful for detecting protein complexes in PPI networks.

Description: Background: Non-adherence to Antiretroviral Treatment (ART) is strongly associated with virologic rebound and drug resistance. Studies have shown that the most frequently mentioned reason for missing ART doses is the forgetfulness of patients to take their medications on time. Therefore using communication devices as reminder tools, for example alarms, pagers, text messages and telephone calls could improve adherence to ART. The aim of this study is to measure access to cellphones, willingness to receive text message medication reminders and to identify associated factors of ART patients at the University of Gondar Hospital, in North West Ethiopia. Methods: An institution based cross sectional quantitative study was conducted among 423 patients on ART during April 2014. Data were collected using structured interviewer-administered questionnaires. Data entry and analysis were done using Epi-Info version 7 and SPSS version 20 respectively. Descriptive statistics and multivariable logistic regression analysis were used to describe the characteristic of the sample and identify factors associated with the willingness to receive text message medication reminders. Results: A total of 415 (98 % response rate) respondents participated in the interview. The majority of respondents 316 (76.1 %) owned a cellphone, and 161(50.9 %) were willing to receive text message medication reminders. Positively associated factors to the willingness were the following: Younger age group (AOR = 5.18, 95 % CI: [1.69, 15.94]), having secondary or higher education (AOR = 4.61, 95 % CI: [1.33, 16.01]), using internet (AOR = 3.94, 95 % CI: [1.67, 9.31]), not disclosing HIV status to anyone other than HCP (Health Care Provider) (AOR = 3.03, 95 % CI: [1.20, 7.61]), availability of radio in dwelling (AOR = 2.74 95 % CI: [1.27, 5.88]), not answering unknown calls (AOR = 2.67, 95 % CI: [1.34, 5.32]), use of cellphone alarm as medication reminder (AOR = 2.22, 95%CI [1.09, 4.52]), and forgetting to take medications (AOR = 2.13, 95 % CI: [1.14, 3.96]). Conclusions: A high proportion of respondents have a cell phone and are willing to use it as medication reminders. Age, educational status and using internet were the main factors that are significantly associated with the willingness of patients to receive text message medication reminders.

Description: A commonly studied means of parameterizing graph problems is the deletion distance from triviality (Guo et al., Parameterized and exact computation, Springer, Berlin, pp. 162–173, 2004 ), which counts vertices that need to be deleted from a graph to place it in some class for which efficient algorithms are known. In the context of graph isomorphism, we define triviality to mean a graph with maximum degree bounded by a constant, as such graph classes admit polynomial-time isomorphism tests. We generalise deletion distance to a measure we call elimination distance to triviality, based on elimination trees or tree-depth decompositions. We establish that graph canonisation, and thus graph isomorphism, is \(\mathsf {FPT}\) when parameterized by elimination distance to bounded degree, extending results of Bouland et al. (Parameterized and exact computation, Springer, Berlin, pp. 218–230, 2012 ).

Description: Recent advances in drift analysis have given us better and better tools for understanding random processes, including the run time of randomized search heuristics. In the setting of multiplicative drift we do not only have excellent bounds on the expected run time, but also more general results showing the strong concentration of the run time. In this paper we investigate the setting of additive drift under the assumption of strong concentration of the “step size” of the process. Under sufficiently strong drift towards the goal we show a strong concentration of the hitting time. In contrast to this, we show that in the presence of small drift a Gambler’s-Ruin-like behavior of the process overrides the influence of the drift, leading to a maximal movement of about \(\sqrt{t}\) steps within t iterations. Finally, in the presence of sufficiently strong negative drift the hitting time is superpolynomial with high probability; this corresponds to the well-known Negative Drift Theorem.

Description: Binets and trinets are phylogenetic networks with two and three leaves, respectively. Here we consider the problem of deciding if there exists a binary level-1 phylogenetic network displaying a given set  \(\mathbb {T}\) of binary binets or trinets over a taxon set  X , and constructing such a network whenever it exists. We show that this is NP-hard for trinets but polynomial-time solvable for binets. Moreover, we show that the problem is still polynomial-time solvable for inputs consisting of binets and trinets as long as the cycles in the trinets have size three. Finally, we present an  \(O(3^{|X|} poly(|X|))\) time algorithm for general sets of binets and trinets. The latter two algorithms generalise to instances containing level-1 networks with arbitrarily many leaves, and thus provide some of the first supernetwork algorithms for computing networks from a set of rooted phylogenetic networks.

Description: We consider stochastic versions of OneMax and LeadingOnes and analyze the performance of evolutionary algorithms with and without populations on these problems. It is known that the ( \(1+1\) ) EA on OneMax performs well in the presence of very small noise, but poorly for higher noise levels. We extend these results to LeadingOnes and to many different noise models, showing how the application of drift theory can significantly simplify and generalize previous analyses. Most surprisingly, even small populations (of size \(\varTheta (\log n)\) ) can make evolutionary algorithms perform well for high noise levels, well outside the abilities of the ( \(1+1\) ) EA. Larger population sizes are even more beneficial; we consider both parent and offspring populations. In this sense, populations are robust in these stochastic settings.

Description: Since Tinhofer proposed the MinGreedy algorithm for maximum cardinality matching in 1984, several experimental studies found the randomized algorithm to perform excellently for various classes of random graphs and benchmark instances. In contrast, only few analytical results are known. We show that MinGreedy cannot improve on the trivial approximation ratio of  \(\frac{1}{2}\) whp., even for bipartite graphs. Our hard inputs seem to require a small number of high-degree nodes. This motivates an investigation of greedy algorithms on graphs with maximum degree  \(\varDelta \) : we show that  MinGreedy achieves a  \({\frac{{\varDelta }-1}{2{\varDelta }-3}} \) -approximation for graphs with  \({\varDelta } {=} 3\) and for \(\varDelta \) -regular graphs, and a guarantee of  \({\frac{{\varDelta }-1/2}{2{\varDelta }-2}} \) for graphs with maximum degree  \({\varDelta } \) . Interestingly, our bounds even hold for the deterministic MinGreedy that breaks all ties arbitrarily. Moreover, we investigate the limitations of the greedy paradigm, using the model of priority algorithms introduced by Borodin, Nielsen, and Rackoff. We study deterministic priority algorithms and prove a  \({\frac{{\varDelta }-1}{2{\varDelta }-3}}\) -inapproximability result for graphs with maximum degree  \({\varDelta } \) ; thus, these greedy algorithms do not achieve a  \(\frac{1}{2} {+} \varepsilon \) -approximation and in particular the  \(\frac{2}{3}\) -approximation obtained by the deterministic MinGreedy for  \({\varDelta } {=} 3\) is optimal in this class. For  k -uniform hypergraphs we show a tight  \(\frac{1}{k}\) -inapproximability bound. We also study fully randomized priority algorithms and give a  \(\frac{5}{6}\) -inapproximability bound. Thus, they cannot compete with matching algorithms of other paradigms.

Description: We discuss how string sorting algorithms can be parallelized on modern multi-core shared memory machines. As a synthesis of the best sequential string sorting algorithms and successful parallel sorting algorithms for atomic objects, we first propose string sample sort. The algorithm makes effective use of the memory hierarchy, uses additional word level parallelism, and largely avoids branch mispredictions. Then we focus on NUMA architectures, and develop parallel multiway LCP-merge and -mergesort to reduce the number of random memory accesses to remote nodes. Additionally, we parallelize variants of multikey quicksort and radix sort that are also useful in certain situations. As base-case sorter for LCP-aware string sorting we describe sequential LCP-insertion sort which calculates the LCP array and accelerates its insertions using it. Comprehensive experiments on five current multi-core platforms are then reported and discussed. The experiments show that our parallel string sorting implementations scale very well on real-world inputs and modern machines.

Description: Background: Prenatal screening tests for Down syndrome (DS) are routine in many developed countries and new tests are rapidly becoming available. Decisions about prenatal screening are increasingly complex with each successive test, and pregnant women need information about risks and benefits as well as clarity about their values. Decision aids (DAs) can help healthcare providers support women in this decision. Using an environmental scan, we aimed to identify publicly available DAs focusing on prenatal screening/diagnosis for Down syndrome that provide effective support for decision making. Methods: Data sources searched were the Decision Aids Library Inventory (DALI) of the Ottawa Patient Decision Aids Research Group at the Ottawa Health Research Institute; Google searches on the internet; professional organizations, academic institutions and other experts in the field; and references in existing systematic reviews on DAs. Eligible DAs targeted pregnant women, focused on prenatal screening and/or diagnosis, applied to tests for fetal abnormalities or aneuploidies, and were in French, English, Spanish or Portuguese. Pairs of reviewers independently identified eligible DAs and extracted characteristics including the presence of practical decision support tools and features to aid comprehension. They then performed quality assessment using the 16 minimum standards established by the International Patient Decision Aids Standards (IPDASi v4.0). Results: Of 543 potentially eligible DAs (512 in DALI, 27 from experts, and four on the internet), 23 were eligible and 20 were available for data extraction. DAs were developed from 1996 to 2013 in six countries (UK, USA, Canada, Australia, Sweden, and France). Five DAs were for prenatal screening, three for prenatal diagnosis and 12 for both). Eight contained values clarification methods (personal worksheets). The 20 DAs scored a median of 10/16 (range 6–15) on the 16 IPDAS minimum standards.DiscussionNone of the 20 included DAs met all 16 IPDAS minimum standards, and few included practical decision support tools or aids to comprehension. Conclusions: Our results indicate there is a need for DAs that effectively support decision making regarding prenatal testing for Down syndrome, especially in light of the recently available non-invasive prenatal screening tests.

Description: Background: A plethora of publicly available biomedical resources do currently exist and are constantly increasing at a fast rate. In parallel, specialized repositories are been developed, indexing numerous clinical and biomedical tools. The main drawback of such repositories is the difficulty in locating appropriate resources for a clinical or biomedical decision task, especially for non-Information Technology expert users. In parallel, although NLP research in the clinical domain has been active since the 1960s, progress in the development of NLP applications has been slow and lags behind progress in the general NLP domain.The aim of the present study is to investigate the use of semantics for biomedical resources annotation with domain specific ontologies and exploit Natural Language Processing methods in empowering the non-Information Technology expert users to efficiently search for biomedical resources using natural language. Methods: A Natural Language Processing engine which can “translate” free text into targeted queries, automatically transforming a clinical research question into a request description that contains only terms of ontologies, has been implemented. The implementation is based on information extraction techniques for text in natural language, guided by integrated ontologies. Furthermore, knowledge from robust text mining methods has been incorporated to map descriptions into suitable domain ontologies in order to ensure that the biomedical resources descriptions are domain oriented and enhance the accuracy of services discovery. The framework is freely available as a web application at (http://calchas.ics.forth.gr/). Results: For our experiments, a range of clinical questions were established based on descriptions of clinical trials from the ClinicalTrials.gov registry as well as recommendations from clinicians. Domain experts manually identified the available tools in a tools repository which are suitable for addressing the clinical questions at hand, either individually or as a set of tools forming a computational pipeline. The results were compared with those obtained from an automated discovery of candidate biomedical tools. For the evaluation of the results, precision and recall measurements were used. Our results indicate that the proposed framework has a high precision and low recall, implying that the system returns essentially more relevant results than irrelevant. Conclusions: There are adequate biomedical ontologies already available, sufficiency of existing NLP tools and quality of biomedical annotation systems for the implementation of a biomedical resources discovery framework, based on the semantic annotation of resources and the use on NLP techniques. The results of the present study demonstrate the clinical utility of the application of the proposed framework which aims to bridge the gap between clinical question in natural language and efficient dynamic biomedical resources discovery.

Description: Stochastic boolean function evaluation (SBFE) is the problem of determining the value of a given boolean function f on an unknown input x , when each bit \(x_i\) of x can only be determined by paying a given associated cost \(c_i\) . Further, x is drawn from a given product distribution: for each \(x_i\) , \(\mathbf{Pr}[x_i=1] = p_i\) and the bits are independent. The goal is to minimize the expected cost of evaluation. In this paper, we study the complexity of the SBFE problem for classes of DNF formulas. We consider both exact and approximate versions of the problem for subclasses of DNF, for arbitrary costs and product distributions, and for unit costs and/or the uniform distribution.

Description: Background: Although evidence has suggested that computerized drug-drug interaction alert systems may reduce the occurrence of drug-drug interactions, the numerous reminders and alerts generated by such systems could represent an excessive burden for clinicians, resulting in a high override rate of not only unimportant, but also important alerts. Methods: We analyzed physicians’ responses to alerts of relative contraindications and contraindications for coadministration in a computerized drug-drug interaction alert system at Hokkaido University Hospital. In this system, the physician must enter a password to override an alert and continue an order. All of the drug-drug interaction alerts generated between December 2011 and November 2012 at Hokkaido University Hospital were included in this study. Results: The system generated a total of 170 alerts of relative contraindications and contraindication for coadministration; 59 (34.7 %) of the corresponding orders were cancelled after the alert was accepted, and 111 (65.3 %) were overridden. The most frequent contraindication alert was for the combination of 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors and fibrates. No incidents involving drug-drug interactions were reported among patients who were prescribed contraindicated drug pairs after an override. Conclusions: Although computerized drug-drug interaction alert systems that require password overrides appear useful for promoting medication safety, having to enter passwords to override alerts may represent an excessive burden for the prescribing physician. Therefore, both patient safety and physicians’ workloads should be taken into consideration in future designs of computerized drug-drug interaction alert systems.

Description: Background: When new pharmaceutical products appear on the market, physicians need to know whether they are likely to be useful in their practices. Physicians currently obtain most of their information about the market release and properties of new drugs from pharmaceutical industry representatives. However, the official information contained in the summary of product characteristics (SPCs) and evaluation reports from health agencies, provide a more complete view of the potential value of new drugs, although they can be long and difficult to read. The main objective of this work was to design a prototype computer program to facilitate the objective appraisal of the potential value of a new pharmaceutical product by physicians. This prototype is based on the modeling of pharmaceutical innovations described in a previous paper. Methods: The interface was designed to allow physicians to develop a rapid understanding of the value of a new drug for their practices. We selected five new pharmaceutical products, to illustrate the function of this prototype. We considered only the texts supplied by national or international drug agencies at the time of market release. The perceived usability of the prototype was evaluated qualitatively, except for the System Usability Scale (SUS) score evaluation, by 10 physicians differing in age and medical background. Results: The display is based on the various axes of the conceptual model of pharmaceutical innovations. The user can select three levels of detail when consulting this information (highly synthetic, synthetic and detailed). Tables provide a comparison of the properties of the new pharmaceutical product with those of existing drugs, if available for the same indication, in terms of efficacy, safety and ease of use.The interface was highly appreciated by evaluators, who found it easy to understand and suggested no other additions of important, internationally valid information. The mean System Usability Scale score for the 10 physicians was 82, corresponding to a “good” user interface. Conclusions: This work led us to propose the selection, grouping, and mode of presentation for various types of knowledge on pharmaceutical innovations in a way that was appreciated by evaluators. It provides physicians with readily accessible objective information about new drugs.

Description: Background: Clinical trials apply standards approved by regulatory agencies for Electronic Data Capture (EDC). Operational Data Model (ODM) from Clinical Data Interchange Standards Consortium (CDISC) is commonly used. Electronic Health Record (EHR) systems for patient care predominantly apply HL7 standards, specifically Clinical Document Architecture (CDA). In recent years more and more patient data is processed in electronic form. Results: An open source reference implementation was designed and implemented to convert forms between ODM and CDA format. There are limitations of this conversion method due to different scope and design of ODM and CDA. Specifically, CDA has a multi-level hierarchical structure and CDA nodes can contain both XML values and XML attributes. Conclusions: Automated transformation of ODM files to CDA and vice versa is technically feasible in principle.

Description: Background: An academic, community medicine partnership was established to build a phenotype-to-outcome model targeting chronic pain. This model will be used to drive clinical decision support for pain medicine in the community setting. The first step in this effort is an examination of the electronic health records (EHR) from clinics that treat chronic pain. The biopsychosocial components provided by both patients and care providers must be of sufficient scope to populate the spectrum of patient types, treatment modalities, and possible outcomes. Methods: The patient health records from a large Midwest pain medicine practice (Michigan Pain Consultants, PC) contains physician notes, administrative codes, and patient-reported outcomes (PRO) on over 30,000 patients during the study period spanning 2010 to mid-2014. The PRO consists of a regularly administered Pain Health Assessment (PHA), a biopsychosocial, demographic, and symptomology questionnaire containing 163 items, which is completed approximately every six months with a compliance rate of over 95 %. The biopsychosocial items (74 items with Likert scales of 0–10) were examined by exploratory factor analysis and descriptive statistics to determine the number of independent constructs available for phenotypes and outcomes. Pain outcomes were examined both in the aggregate and the mean of longitudinal changes in each patient. Results: Exploratory factor analysis of the intake PHA revealed 15 orthogonal factors representing pain levels; physical, social, and emotional functions; the effects of pain on these functions; vitality and health; and measures of outcomes and satisfaction. Seven items were independent of the factors, offering unique information. As an exemplar of outcomes from the follow-up PHAs, patients reported approximately 60 % relief in their pain. When examined in the aggregate, patients showed both a decrease in pain levels and an increase in coping skills with an increased number of visits. When examined individually, 80-85 % of patients presenting with the highest pain levels reported improvement by approximately two points on an 11-point pain scale. Conclusions: We conclude that the data available in a community practice can be a rich source of biopsychosocial information relevant to the phenotypes of chronic pain. It is anticipated that phenotype linkages to best treatments and outcomes can be constructed from this set of records.

Description: Health information is increasingly being digitally stored and exchanged. The public is regularly collecting and storing health-related data on their own electronic devices and in the cloud. Diabetes prevention...

Description: Electronic medical records (EMR) offer a major potential for secondary use of data for research which can improve the safety, quality and efficiency of healthcare. They also enable the measurement of disease b...

Description: Interval graphs are intersection graphs of closed intervals of the real-line. The well-known computational problem, called recognition , asks whether an input graph G can be represented by closed intervals, i.e., whether G is an interval graph. There are several linear-time algorithms known for recognizing interval graphs, the oldest one is by Booth and Lueker (J Comput Syst Sci 13:335–379, 1976 ) based on PQ-trees. In this paper, we study a generalization of recognition, called partial representation extension . The input of this problem consists of a graph G with a partial representation \({{{\mathcal {R}}}}'\) fixing the positions of some intervals. The problem asks whether it is possible to place the remaining interval and create an interval representation \({{{\mathcal {R}}}}\) of the entire graph G extending \({{{\mathcal {R}}}}'\) . We generalize the characterization of interval graphs by Fulkerson and Gross (Pac J Math 15:835–855, 1965 ) to extendible partial representations. Using it, we give a linear-time algorithm for partial representation extension based on a reordering problem of PQ-trees.

Description: Epileptic seizure is a serious health problem in the world and there is a huge population suffering from it every year. If an algorithm could automatically detect seizures and deliver the patient therapy or no...

Description: Learning deep representations of clinical events based on their distributions in electronic health records has been shown to allow for subsequent training of higher-performing predictive models compared to the...

Description: Glands are vital structures found throughout the human body and their structure and function are affected by many diseases. The ability to segment and detect glands among other types of tissues is important fo...

Description: People want to live independently, but too often disabilities or advanced age robs them of the ability to do the necessary activities of daily living (ADLs). Finding relationships between electromyograms measu...

Description: Cancer is a disease characterized as an uncontrolled growth of abnormal cells that invades neighboring tissues and destroys them. Lung cancer is the primary cause of cancer-related deaths in the world, and it ...

Description: Healthcare researchers often use multiple healthcare survey instruments to examine a particular patient symptom. The use of multiple instruments can pose some interesting research questions, such as whether th...

Description: Modern data management systems often need to deal with massive, dynamic and inherently distributed data sources. We collect the data using a distributed network, and at the same time try to maintain a global view of the data at a central coordinator using a minimal amount of communication. Such applications have been captured by the distributed monitoring model which has attracted a lot of attention in recent years. In this paper we investigate the monitoring of the entropy functions, which are very useful in network monitoring applications such as detecting distributed denial-of-service attacks. Our results improve the previous best results by Arackaparambil et al. in ICLP 1: 95–106 ( 2009 ). Our technical contribution also includes implementing the celebrated AMS sampling method (by Alon et al. in J Comput Syst Sci 58(1): 137–147 1999 ) in the distributed monitoring model, which could be of independent interest.

Description: In the Boundary Labeling problem, we are given a set of  n points, referred to as sites , inside an axis-parallel rectangle  R , and a set of  n pairwise disjoint rectangular labels that are attached to  R from the outside. The task is to connect the sites to the labels by non-intersecting rectilinear paths, so-called leaders , with at most one bend. In this paper, we study the Multi-Sided Boundary Labeling problem, with labels lying on at least two sides of the enclosing rectangle. We present a polynomial-time algorithm that computes a crossing-free leader layout if one exists. So far, such an algorithm has only been known for the cases in which labels lie on one side or on two opposite sides of  R (here a crossing-free solution always exists). The case where labels may lie on adjacent sides is more difficult. We present efficient algorithms for testing the existence of a crossing-free leader layout that labels all sites and also for maximizing the number of labeled sites in a crossing-free leader layout. For two-sided boundary labeling with adjacent sides, we further show how to minimize the total leader length in a crossing-free layout.

Description: In this paper we consider the problem of the strict self-assembly of infinite fractals within tile self-assembly. In particular, we provide tile assembly algorithms for the assembly of a Sierpinski triangle and the discrete Sierpinski carpet within a class of models we term the h - handed assembly model ( h -HAM), which generalizes the 2-HAM to allow up to h assemblies to combine in a single assembly step. Despite substantial consideration, no purely growth self-assembly model has yet been shown to strictly assemble an infinite fractal without significant modification to the fractal shape. In this paper we not only achieve this, but in the case of the Sierpinski carpet are able to achieve it within the 2-HAM, one of the most well studied tile assembly models in the literature. Our specific results are as follows: We provide a 6-HAM construction for a Sierpinski triangle that works at scale factor 1, 30 tile types, and assembles the fractal in a near perfect way in which all intermediate assemblies are finite-sized iterations of the recursive fractal. We further assemble a Sierpinski triangle within the 3-HAM at scale factor 3 and 990 tile types. For the Sierpinski carpet, we present a 2-HAM result that works at scale factor 3 and uses 1216 tile types. We further include analysis showing that the aTAM is incapable of strictly assembling the Sierpinski triangle considered in this paper, and that multiple hands are needed for the near-perfect assembly of a Sierpinski triangle and the Sierpinski carpet.

Description: We consider k -Facility Location games, where n strategic agents report their locations on the real line and a mechanism maps them to k facilities. Each agent seeks to minimize his connection cost, given by a nonnegative increasing function of his distance to the nearest facility. Departing from previous work, that mostly considers the identity cost function, we are interested in mechanisms without payments that are (group) strategyproof for any given cost function, and achieve a good approximation ratio for the social cost and/or the maximum cost of the agents. We present a randomized mechanism, called Equal Cost , which is group strategyproof and achieves a bounded approximation ratio for all k and n , for any given concave cost function. The approximation ratio is at most 2 for Max Cost and at most n for Social Cost . To the best of our knowledge, this is the first mechanism with a bounded approximation ratio for instances with \(k \ge 3\) facilities and any number of agents. Our result implies an interesting separation between deterministic mechanisms, whose approximation ratio for Max Cost jumps from 2 to unbounded when k increases from 2 to 3, and randomized mechanisms, whose approximation ratio remains at most 2 for all k . On the negative side, we exclude the possibility of a mechanism with the properties of Equal Cost for strictly convex cost functions. We also present a randomized mechanism, called Pick the Loser , which applies to instances with k facilities and only \(n = k+1\) agents. For any given concave cost function, Pick the Loser is strongly group strategyproof and achieves an approximation ratio of 2 for Social Cost .

Description: We give a deterministic #SAT algorithm for de Morgan formulas of size up to \(n^{2.63}\) , which runs in time \(2^{n-n^{{\varOmega }(1)}}\) . This improves upon the deterministic #SAT algorithm of Chen et al. (Proceedings of the twenty-ninth annual IEEE conference on computational complexity, 2014 ), which has similar running time but works only for formulas of size less than \(n^{2.5}\) . Our new algorithm is based on the shrinkage of de Morgan formulas under random restrictions, shown by Paterson and Zwick (Random Struct Algorithms 4(2):135–150, 1993 ). We prove a concentrated and constructive version of their shrinkage result. Namely, we give a deterministic polynomial-time algorithm that selects variables in a given de Morgan formula so that, with high probability over the random assignments to the chosen variables, the original formula shrinks in size, when simplified using a given deterministic polynomial-time formula-simplification algorithm.

Description: We consider Conditional random fields ( CRFs ) with pattern-based potentials defined on a chain. In this model the energy of a string (labeling) \(x_1\ldots x_n\) is the sum of terms over intervals [ i ,  j ] where each term is non-zero only if the substring \(x_i\ldots x_j\) equals a prespecified pattern w . Such CRFs can be naturally applied to many sequence tagging problems. We present efficient algorithms for the three standard inference tasks in a CRF, namely computing (i) the partition function, (ii) marginals, and (iii) computing the MAP. Their complexities are respectively \(O(\textit{nL})\) , \(O(\textit{nL} \ell _{\max })\) and \(O(\textit{nL} \min \{|D|,\log (\ell _{\max }\!+\!1)\})\) where L is the combined length of input patterns, \(\ell _{\max }\) is the maximum length of a pattern, and D is the input alphabet. This improves on the previous algorithms of Ye et al. (NIPS, 2009 ) whose complexities are respectively \(O(\textit{nL} |D|)\) , \(O\left( n |\varGamma | L^2 \ell _{\max }^2\right) \) and \(O(\textit{nL} |D|)\) , where \(|\varGamma |\) is the number of input patterns. In addition, we give an efficient algorithm for sampling, and revisit the case of MAP with non-positive weights.

Description: Estimating the number of triangles in graph streams using a limited amount of memory has become a popular topic in the last decade. Different variations of the problem have been studied, depending on whether the graph edges are provided in an arbitrary order or as incidence lists. However, with a few exceptions, the algorithms have considered insert-only streams. We present a new algorithm estimating the number of triangles in dynamic graph streams where edges can be both inserted and deleted. We show that our algorithm achieves better time and space complexity than previous solutions for various graph classes, for example sparse graphs with a relatively small number of triangles. Also, for graphs with constant transitivity coefficient, a common situation in real graphs, this is the first algorithm achieving constant processing time per edge. The result is achieved by a novel approach combining sampling of vertex triples and sparsification of the input graph. In the course of the analysis of the algorithm we present a lower bound on the number of pairwise independent 2-paths in general graphs which might be of independent interest. At the end of the paper we discuss lower bounds on the space complexity of triangle counting algorithms that make no assumptions on the structure of the graph.

Description: We consider the problems of finding optimal identifying codes, (open) locating-dominating sets and resolving sets (denoted Identifying Code , (Open) Open Locating-Dominating Set and Metric Dimension ) of an interval or a permutation graph. In these problems, one asks to distinguish all vertices of a graph by a subset of the vertices, using either the neighbourhood within the solution set or the distances to the solution vertices. Using a general reduction for this class of problems, we prove that the decision problems associated to these four notions are NP-complete, even for interval graphs of diameter 2 and permutation graphs of diameter 2. While Identifying Code and (Open) Locating-Dominating Set are trivially fixed-parameter-tractable when parameterized by solution size, it is known that in the same setting Metric Dimension is W [2]-hard. We show that for interval graphs, this parameterization of Metric Dimension is fixed-parameter-tractable.

Description: The study investigated the feasibility of conducting a future Randomised Controlled Trial (RCT) of a mobile health (mHealth) intervention for weight loss and HbA1c reduction in Type 2 Diabetes Mellitus (T2DM).

Description: A growing number of physicians are using social media as a professional platform for health communication. The purpose of this study was to understand perspectives and experiences of these “early adopter” phys...

Description: The volume of research published in the biomedical domain has increasingly lead to researchers focussing on specific areas of interest and connections between findings being missed. Literature based discovery ...

Description: To facilitate long-term safety surveillance of marketing drugs, many spontaneously reporting systems (SRSs) of ADR events have been established world-wide. Since the data collected by SRSs contain sensitive pe...

Description: Cardiac rehabilitation (CR) can slow or reverse the progression of cardiovascular disease (CVD). However, uptake of community-based CR is very low. E-cardiology, e-health and technology solutions for physical ...

Description: Risk prediction models have been proposed for various diseases and are being improved as new predictors are identified. A major challenge is to determine whether the newly discovered predictors improve risk pr...

Description: Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which compr...

Description: Nearest neighbor (NN) imputation algorithms are efficient methods to fill in missing data where each missing value on some records is replaced by a value obtained from related cases in the whole set of records...

Description: In biomedical research, data sharing and information exchange are very important for improving quality of care, accelerating discovery, and promoting the meaningful secondary use of clinical data. A big concer...

Description: The study on disease-disease association has been increasingly viewed and analyzed as a network, in which the connections between diseases are configured using the source information on interactome maps of bio...