ALBERT

Description: We examine a distributed detection problem in a wireless sensor network, where sensor nodes collaborate to detect a Gaussian signal with an unknown change of power, i.e., a scale parameter. Due to power/bandwidth constraints, we consider the case where each sensor quantizes its observation into a binary digit. The binary data are then transmitted through error-prone wireless links to a fusion center, where a generalized likelihood ratio test (GLRT) detector is employed to perform a global decision. We study the design of a binary quantizer based on an asymptotic analysis of the GLRT. Interestingly, the quantization threshold of the quantizer is independent of the unknown scale parameter. Numerical results are included to illustrate the performance of the proposed quantizer and GLRT in binary symmetric channels (BSCs).

Description: More and more hybrid electric vehicles are driven since they offer such advantages as energy savings and better active safety performance. Hybrid vehicles have two or more power driving systems and frequently switch working condition, so controlling stability is very important. In this work, a two-stage Kalman algorithm method is used to fuse data in hybrid vehicle stability testing. First, the RT3102 navigation system and Dewetron system are introduced. Second, a modeling of data fusion is proposed based on the Kalman filter. Then, this modeling is simulated and tested on a sample vehicle, using Carsim and Simulink software to test the results. The results showed the merits of this modeling.

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: Currently deep learning has made great breakthroughs in visual and speech processing, mainly because it draws lessons from the hierarchical mode that brain deals with images and speech. In the field of NLP, a topic model is one of the important ways for modeling documents. Topic models are built on a generative model that clearly does not match the way humans write. In this paper, we propose Event Model, which is unsupervised and based on the language processing mechanism of neurolinguistics, to model documents. In Event Model, documents are descriptions of concrete or abstract events seen, heard, or sensed by people and words are objects in the events. Event Model has two stages: word learning and dimensionality reduction. Word learning is to learn semantics of words based on deep learning. Dimensionality reduction is the process that representing a document as a low dimensional vector by a linear mode that is completely different from topic models. Event Model achieves state-of-the-art results on document retrieval tasks.

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: Community detection in a complex network is an important problem of much interest in recent years. In general, a community detection algorithm chooses an objective function and captures the communities of the network by optimizing the objective function, and then, one uses various heuristics to solve the optimization problem to extract the interesting communities for the user. In this article, we demonstrate the procedure to transform a graph into points of a metric space and develop the methods of community detection with the help of a metric defined for a pair of points. We have also studied and analyzed the community structure of the network therein. The results obtained with our approach are very competitive with most of the well-known algorithms in the literature, and this is justified over the large collection of datasets. On the other hand, it can be observed that time taken by our algorithm is quite less compared to other methods and justifies the theoretical findings.

Description: A three-step iterative method with fifth-order convergence as a new modification of Newton’s method was presented. This method is for finding multiple roots of nonlinear equation with unknown multiplicity m whose multiplicity m is the highest multiplicity. Its order of convergence is analyzed and proved. Results for some numerical examples show the efficiency of the new method.

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 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: In this paper, we present three improvements to a three-point third order variant of Newton’s method derived from the Simpson rule. The first one is a fifth order method using the same number of functional evaluations as the third order method, the second one is a four-point 10th order method and the last one is a five-point 20th order method. In terms of computational point of view, our methods require four evaluations (one function and three first derivatives) to get fifth order, five evaluations (two functions and three derivatives) to get 10th order and six evaluations (three functions and three derivatives) to get 20th order. Hence, these methods have efficiency indexes of 1.495, 1.585 and 1.648, respectively which are better than the efficiency index of 1.316 of the third order method. We test the methods through some numerical experiments which show that the 20th order method is very efficient.

Description: Robust small target detection of low signal-to-noise ratio (SNR) is very important in infrared search and track applications for self-defense or attacks. Due to the complex background, current algorithms have some unsolved issues with false alarm rate. In order to reduce the false alarm rate, an infrared small target detection algorithm based on saliency detection and support vector machine was proposed. Firstly, we detect salient regions that may contain targets with phase spectrum Fourier transform (PFT) approach. Then, target recognition was performed in the salient regions. Experimental results show the proposed algorithm has ideal robustness and efficiency for real infrared small target detection applications.

Description: In dynamic propagation environments, beamforming algorithms may suffer from strong interference, steering vector mismatches, a low convergence speed and a high computational complexity. Reduced-rank signal processing techniques provide a way to address the problems mentioned above. This paper presents a low-complexity robust data-dependent dimensionality reduction based on an iterative optimization with steering vector perturbation (IOVP) algorithm for reduced-rank beamforming and steering vector estimation. The proposed robust optimization procedure jointly adjusts the parameters of a rank reduction matrix and an adaptive beamformer. The optimized rank reduction matrix projects the received signal vector onto a subspace with lower dimension. The beamformer/steering vector optimization is then performed in a reduced dimension subspace. We devise efficient stochastic gradient and recursive least-squares algorithms for implementing the proposed robust IOVP design. The proposed robust IOVP beamforming algorithms result in a faster convergence speed and an improved performance. Simulation results show that the proposed IOVP algorithms outperform some existing full-rank and reduced-rank algorithms with a comparable complexity.

Description: Recently, wireless sensor networks (WSNs) have drawn great interest due to their outstanding monitoring and management potential in medical, environmental and industrial applications. Most of the applications that employ WSNs demand all of the sensor nodes to run on a common time scale, a requirement that highlights the importance of clock synchronization. The clock synchronization problem in WSNs is inherently related to parameter estimation. The accuracy of clock synchronization algorithms depends essentially on the statistical properties of the parameter estimation algorithms. Recently, studies dedicated to the estimation of synchronization parameters, such as clock offset and skew, have begun to emerge in the literature. The aim of this article is to provide an overview of the state-of-the-art clock synchronization algorithms for WSNs from a statistical signal processing point of view. This article focuses on describing the key features of the class of clock synchronization algorithms that exploit the traditional two-way message (signal) exchange mechanism. Upon introducing the two-way message exchange mechanism, the main clock offset estimation algorithms for pairwise synchronization of sensor nodes are first reviewed, and their performance is compared. The class of fully-distributed clock offset estimation algorithms for network-wide synchronization is then surveyed. The paper concludes with a list of open research problems pertaining to clock synchronization of WSNs.

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: In this paper we investigate some parallel variants of Broyden’s method and, for the basic variant, we present its convergence properties. The main result is that the behavior of the considered parallel Broyden’s variants is comparable with the classical parallel Newton method, and significantly better than the parallel Cimmino method, both for linear and nonlinear cases. The considered variants are also compared with two more recently proposed parallel Broyden’s method. Some numerical experiments are presented to illustrate the advantages and limits of the proposed algorithms.

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: The sign least mean square with reweighted L1-norm constraint (SLMS-RL1) algorithm is an attractive sparse channel estimation method among Gaussian mixture model (GMM) based algorithms for use in impulsive noise environments. The channel sparsity can be exploited by SLMS-RL1 algorithm based on appropriate reweighted factor, which is one of key parameters to adjust the sparse constraint for SLMS-RL1 algorithm. However, to the best of the authors’ knowledge, a reweighted factor selection scheme has not been developed. This paper proposes a Monte-Carlo (MC) based reweighted factor selection method to further strengthen the performance of SLMS-RL1 algorithm. To validate the performance of SLMS-RL1 using the proposed reweighted factor, simulations results are provided to demonstrate that convergence speed can be reduced by increasing the channel sparsity, while the steady-state MSE performance only slightly changes with different GMM impulsive-noise strengths.

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: Der Gerichtshof der Europäischen Union hat mit Urteil vom 6. Oktober 2015 die Entscheidung der Kommission vom 26.7.2000 (2000/520/EG) zur Angemessenheit des von den Grundsätzen des „sicheren Hafens“ und der diesbezüglichen „Häufig gestellten Fragen“ (FAQ) gewährleisteten Schutzes, vorgelegt vom Handelsministerium der USA, für ungültig erklärt. 1 Der folgende Beitrag erläutert die Hintergründe der Entscheidung, fasst deren wesentliche Punkte noch einmal zusammen und gibt einen ersten Ausblick, welche Konsequenzen aus der Entscheidung zu ziehen sind.

Description: Datenschutz und Datensicherheit bilden die Eckpfeiler im Umgang mit personenbezogenen Daten. Auch wenn viele Unternehmen hinsichtlich dieser Themen sensibilisiert sind, ist die unfreiwillige Preisgabe von personenbezogenen Daten an Dritte nicht völlig ausgeschlossen. Der folgende Beitrag befasst sich daher mit der Frage der Bußgeldbewehrtheit von Datenpannen und geht dabei insbesondere auf den Begriff der Verarbeitung i. S. v. § 3 Abs. 4 BDSG ein.

Description: Nachdem die Kommission und das Parlament bereits ihre Entwürfe der Datenschutz-Grundverordnung veröffentlicht hatten, folgte im Juni 2015 der Entwurf des Rates der Europäischen Union, wobei sich immer mehr abzeichnet, wie die Reform des europäischen Datenschutzrechts am Ende aussehen wird. So muss insbesondere bei der Durchsetzung und Sanktionierung mit erheblichen praxisrelevanten Veränderungen gerechnet werden.

Description: We present a local convergence analysis of an eighth order three step methodin order to approximate a locally unique solution of nonlinear equation in a Banach spacesetting. In an earlier study by Sharma and Arora (2015), the order of convergence wasshown using Taylor series expansions and hypotheses up to the fourth order derivative oreven higher of the function involved which restrict the applicability of the proposed scheme.However, only first order derivative appears in the proposed scheme. In order to overcomethis problem, we proposed the hypotheses up to only the first order derivative. In this way,we not only expand the applicability of the methods but also propose convergence domain.Finally, where earlier studies cannot be applied, a variety of concrete numerical examplesare proposed to obtain the solutions of nonlinear equations. Our study does not exhibit thistype of problem/restriction.

Description: Lung cancer continues to rank as the leading cause of cancer deaths worldwide. One of the most promising techniques for early detection of cancerous cells relies on sputum cell analysis. This was the motivation behind the design and the development of a new computer aided diagnosis (CAD) system for early detection of lung cancer based on the analysis of sputum color images. The proposed CAD system encompasses four main processing steps. First is the preprocessing step which utilizes a Bayesian classification method using histogram analysis. Then, in the second step, mean shift segmentation is applied to segment the nuclei from the cytoplasm. The third step is the feature analysis. In this step, geometric and chromatic features are extracted from the nucleus region. These features are used in the diagnostic process of the sputum images. Finally, the diagnosis is completed using an artificial neural network and support vector machine (SVM) for classifying the cells into benign or malignant. The performance of the system was analyzed based on different criteria such as sensitivity, specificity and accuracy. The evaluation was carried out using Receiver Operating Characteristic (ROC) curve. The experimental results demonstrate the efficiency of the SVM classifier over other classifiers, with 97% sensitivity and accuracy as well as a significant reduction in the number of false positive and false negative rates.

Description: Near-infrared spectroscopy (NIRS) enables the non-invasive measurement of changes in hemodynamics and oxygenation in tissue. Changes in light-coupling due to movement of the subject can cause movement artifacts (MAs) in the recorded signals. Several methods have been developed so far that facilitate the detection and reduction of MAs in the data. However, due to fixed parameter values (e.g., global threshold) none of these methods are perfectly suitable for long-term (i.e., hours) recordings or were not time-effective when applied to large datasets. We aimed to overcome these limitations by automation, i.e., data adaptive thresholding specifically designed for long-term measurements, and by introducing a stable long-term signal reconstruction. Our new technique (“acceleration-based movement artifact reduction algorithm”, AMARA) is based on combining two methods: the “movement artifact reduction algorithm” (MARA, Scholkmann et al. Phys. Meas. 2010, 31, 649–662), and the “accelerometer-based motion artifact removal” (ABAMAR, Virtanen et al. J. Biomed. Opt. 2011, 16, 087005). We describe AMARA in detail and report about successful validation of the algorithm using empirical NIRS data, measured over the prefrontal cortex in adolescents during sleep. In addition, we compared the performance of AMARA to that of MARA and ABAMAR based on validation data.

Description: Der datenschutzrechtliche Zweckbindungsgrundsatz wurde vor einiger Zeit 1 in den Medien hitzig 2 diskutiert. Anlass gab die Veröffentlichung des aktuellen Ratsentwurfs der Datenschutzgrundverordnung durch European Digital Rights. 3 Unter anderen berichtete der Tagesspiegel, dass durch den aktuellen Entwurf das Zweckbindungsprinzip ausgehebelt werden würde. 4 Der folgende Beitrag möchte mit Blick auf die jeweils verfassungsrechtliche Bedeutung den gesetzgeberischen Spielraum bei der Umsetzung des Zweckbindungsprinzips beleuchten.

Description: Im Zusammenhang mit einer vom Bundesministerium für Gesundheit propagierten „Entbürokratisierung in der Pflege“ mit dem Ziel des „Abbaus von Bürokratie in der Pflegedokumentation“ könnten die auch in Pflegeeinrichtungen nicht mehr wegzudenkenden IT-Systeme eine große Rolle spielen. Bei der Umstellung auf bzw. der Einführung von digitalisierter Pflegedokumentation bestehen aber gleichwohl datenschutzrechtliche Aspekte, die nicht unberücksichtigt bleiben dürfen. Dies gilt insbesondere vor dem Hintergrund, dass es sich bei den in der Pflegedokumentation enthaltenen Informationen vielfach um Gesundheitsdaten der Pflegebedürftigen handelt. 1

Description: This paper focuses on the parameter identification problem for Wiener nonlinear dynamic systems with moving average noises. In order to improve the convergence rate, the gradient-based iterative algorithm is presented by replacing the unmeasurable variables with their corresponding iterative estimates, and to compute iteratively the noise estimates based on the obtained parameter estimates. The simulation results show that the proposed algorithm can effectively estimate the parameters of Wiener systems with moving average noises.

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: Größter Innovationstreiber moderner vernetzter Fahrzeuge ist die Informationstechnologie. Jedoch ergeben sich hierdurch auch neue Bedrohungen für IT-Sicherheit und Datenschutz. In diesem Artikel wird ein Überblick über vernetzte Fahrzeuge, mögliche Anwendungen, die benötigten Daten und die sich ergebenden Bedrohungen gegeben. Weiterhin werden Herausforderungen für die aktuelle Forschung identifiziert.

Description: Aus der Vernetzung des Autos ergeben sich vielfältige Datenschutzfragen. Inwieweit lassen sich die Erfahrungen mit Internet und Smartphones übertragen?

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: Der „Pay-as-you-drive“-Tarif hat Einzug in den deutschen Versicherungsmarkt gehalten. Mit ihm kommt es zu einer neuen Dimension der Datenerhebung im Alltagsleben. Dadurch stellen sich zahlreiche Fragen rund um das Recht der Datenverarbeitung, die für die Zukunft reichlich Diskussionsstoff beinhalten.

Description: Facebook hat wieder einmal seine Bedingungen und Richtlinien geändert–und ist offensichtlich mächtig stolz darauf. Grund genug, Facebook auf diesem Wege einmal eine kurze Rückmeldung zur neuen Datenrichtlinie zu geben.

Description: In this paper, the dynamical behavior of different optimal iterative schemes for solving nonlinear equations with increasing order, is studied. The tendency of the complexity of the Julia set is analyzed and referred to the fractal dimension. In fact, this fractal dimension can be shown to be a powerful tool to compare iterative schemes that estimate the solution of a nonlinear equation. Based on the box-counting algorithm, several iterative derivative-free methods of different convergence orders are compared.

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: Clustering is a fundamental task in data mining. Affinity propagation clustering (APC) is an effective and efficient clustering technique that has been applied in various domains. APC iteratively propagates information between affinity samples, updates the responsibility matrix and availability matrix, and employs these matrices to choose cluster centers (or exemplars) of respective clusters. However, since it mainly uses negative Euclidean distance between exemplars and samples as the similarity between them, it is difficult to identify clusters with complex structure. Therefore, the performance of APC deteriorates on samples distributed with complex structure. To mitigate this problem, we propose an improved APC based on a path-based similarity (APC-PS). APC-PS firstly utilizes negative Euclidean distance to find exemplars of clusters. Then, it employs the path-based similarity to measure the similarity between exemplars and samples, and to explore the underlying structure of clusters. Next, it assigns non-exemplar samples to their respective clusters via that similarity. Our empirical study on synthetic and UCI datasets shows that the proposed APC-PS significantly outperforms original APC and other related approaches.