medplot: A Web Application for Dynamic Summary and Analysis of Longitudinal Medical Data Based on R

In biomedical studies the patients are often evaluated numerous times and a large number of variables are recorded at each time-point. Data entry and manipulation of longitudinal data can be performed using spreadsheet programs, which usually include some data plotting and analysis capabilities and are straightforward to use, but are not designed for the analyses of complex longitudinal data. Specialized statistical software offers more flexibility and capabilities, but first time users with biomedical background often find its use difficult. We developed medplot, an interactive web application that simplifies the exploration and analysis of longitudinal data. The application can be used to summarize, visualize and analyze data by researchers that are not familiar with statistical programs and whose knowledge of statistics is limited. The summary tools produce publication-ready tables and graphs. The analysis tools include features that are seldom available in spreadsheet software, such as correction for multiple testing, repeated measurement analyses and flexible non-linear modeling of the association of the numerical variables with the outcome. medplot is freely available and open source, it has an intuitive graphical user interface (GUI), it is accessible via the Internet and can be used within a web browser, without the need for installing and maintaining programs locally on the user’s computer. This paper describes the application and gives detailed examples describing how to use the application on real data from a clinical study including patients with early Lyme borreliosis.     

ConfocalCheck - A Software Tool for the Automated Monitoring of Confocal Microscope Performance

Laser scanning confocal microscopy has become an invaluable tool in biomedical research but regular quality testing is vital to maintain the system’s performance for diagnostic and research purposes.Although many methods have been devised over the years to characterise specific aspects of a confocal microscope like measuring the optical point spread function or the field illumination, only very few analysis tools are available. Our aim was to develop a comprehensive quality assurance framework ranging from image acquisition to automated analysis and documentation. We created standardised test data to assess the performance of the lasers, the objective lenses and other key components required for optimum confocal operation.The ConfocalCheck software presented here analyses the data fully automatically. It creates numerous visual outputs indicating potential issues requiring further investigation. By storing results in a web browser compatible file format the software greatly simplifies record keeping allowing the operator to quickly compare old and new data and to spot developing trends.We demonstrate that the systematic monitoring of confocal performance is essential in a core facility environment and how the quantitative measurements obtained can be used for the detailed characterisation of system components as well as for comparisons across multiple instruments.     

基因组二代测序数据的自动化分析流程

二代测序技术的发展对测序数据的处理分析提出了很高的要求。目前二代测序数据分析软件很多, 但是绝大多数软件仅能完成单一的分析功能(例如：仅进行序列比对或变异读取或功能注释等), 如何能正确高效地选择整合这些软件已成为迫切需求。文章设计了一套基于perl语言和SGE资源管理的自动化处理流程来分析Illumina平台基因组测序数据。该流程以测序原始序列数据作为输入, 调用业界标准的数据处理软件(如：BWA, Samtools, GATK, ANNOVAR等), 最终生成带有相应功能注释、便于研究者进一步分析的变异位点列表。该流程通过自动化并行脚本控制流程的高效运行, 一站式输出分析结果和报告, 简化了数据分析过程中的人工操作, 大大提高了运行效率。用户只需填写配置文件或使用图形界面输入即可完成全部操作。该工作为广大研究者分析二代测序数据提供了便利的途径。     

Protein function prediction and annotation in an integrated environment powered by web services (AFAWE)

Many sequenced genes are mainly annotated through automatic transfer of annotation from similar sequences. Manual comparison of results or intermediate results from different tools can help avoid wrong annotations and give hints to the function of a gene even if none of the automated tools could return any result. AFAWE simplifies the task of manual functional annotation by running different tools and workflows for automatic function prediction and displaying the results in a way that facilitates comparison. Because all programs are executed as web services, AFAWE is easily extensible and can directly query primary databases, thereby always using the most up-to-date data sources. Visual filters help to distinguish trustworthy results from non-significant results. Furthermore, an interface to add detailed manual annotation to each gene is provided, which can be displayed to other users.     

The Protein Information and Property Explorer 2: gaggle-like exploration of biological proteomic data within one webpage

The Protein Information and Property Explorer 2 (PIPE2) is an enhanced software program and updated web application that aims at providing the proteomic researcher a simple, intuitive user interface through which to begin inquiry into the biological significance of a list of proteins typically produced by MS/MS proteomic processing software. PIPE2 includes an improved interface, new data visualization options, and new data analysis methods for combining disparate, but related, data sets. In particular, PIPE2 has been enhanced to handle multi-dimensional data such as protein abundance, gene expression, and/or interaction data. The current architecture of PIPE2, modeled after that of Gaggle (a programming infrastructure for interoperability between separately developed software tools), contains independent functional units that can be instantiated and pieced together at the user's discretion to form a pipelined analysis workflow. Among these functional units is the Network Viewer component, which adds rich network analysis capabilities to the suite of existing proteomic web resources. Additionally, PIPE2 implements a framework within which new analysis procedures can be easily deployed and distributed over the World Wide Web. PIPE2 is available as a web service at http://pipe2.systemsbiology.net/.     

The Constructor: a web application optimizing cloning strategies based on modules from the registry of standard biological parts

ABSTRACT: Synthetic biology is an emerging field that combines molecular biology with engineering principles, which requires abstraction levels applied to a modular biological componentry. The Registry of Standard Biological Parts harbours such a repository of standardized parts, and thereby facilitates the combination of complex molecular modules to novel genetic circuits and devices. However, since finding the best parts for a pre-determined genetic design can be time consuming, we devised the Constructor, a web tool that recommends the smallest number of cloning steps for pre-designed circuits, and implements user-defined quality checks.We present the Constructor (www.systemsbiology.nl/the_constructor) as a constructive web tool that simplifies the in silico assembly of pre-designed gene circuitries from standard parts, reducing both planning and subsequent cloning time.     

Vesicle Viewer: Online visualization and analysis of small-angle scattering from lipid vesicles

Small-angle X-ray and neutron scattering are among the most powerful experimental techniques for investigating the structure of biological membranes. Much of the critical information contained in small-angle scattering (SAS) data is not easily accessible to researchers who have limited time to analyze results by hand or to nonexperts who may lack the necessary scientific background to process such data. Easy-to-use data visualization software can allow them to take full advantage of their SAS data and maximize the use of limited resources. To this end, we developed an internet-based application called Vesicle Viewer to visualize and analyze SAS data from unilamellar lipid bilayer vesicles. Vesicle Viewer utilizes a modified scattering density profile (SDP) analysis called EZ-SDP in which key bilayer structural parameters, such as area per lipid and bilayer thickness, are easily and robustly determined. Notably, we introduce a bilayer model that is able to describe an asymmetric bilayer, whether it be chemically or isotopically asymmetric. The application primarily uses Django, a Python package specialized for the development of robust web applications. In addition, several other libraries are used to support the more technical aspects of the project; notable examples are Matplotlib (for graphs) and NumPy (for calculations). By eliminating the barrier of downloading and installing software, this web-based application will allow scientists to analyze their own vesicle scattering data using their preferred operating system. The web-based application can be found at https://vesicleviewer.dmarquardt.ca/.     

<Emphasis Type="Italic">ScreenMill</Emphasis>: A freely available software suite for growth measurement,analysis and visualization of high-throughput screen data

Background  

Many high-throughput genomic experiments, such as Synthetic Genetic Array and yeast two-hybrid, use colony growth on solid media as a screen metric. These experiments routinely generate over 100,000 data points, making data analysis a time consuming and painstaking process. Here we describe ScreenMill, a new software suite that automates image analysis and simplifies data review and analysis for high-throughput biological experiments.     

CytoITMprobe: a network information flow plugin for Cytoscape

ABSTRACT: BACKGROUND: Cytoscape is a well-developed flexible platform for visualization, integration and analysis of network data. Apart from the sophisticated graph layout and visualization routines, it hosts numerous user-developed plugins that significantly extend its core functionality. Earlier, we developed a network information flow framework and implemented it as a web application, called ITM Probe. Given a context consisting of one or more user-selected nodes, ITM Probe retrieves other network nodes most related to that context. It requires neither user restriction to subnetwork of interest nor additional and possibly noisy information. However, plugins for Cytoscape with these features do not yet exist. To provide the Cytoscape users the possibility of integrating ITM Probe into their workflows, we developed CytoITMprobe, a new Cytoscape plugin. FINDINGS: CytoITMprobe maintains all the desirable features of ITM Probe and adds additional flexibility not achievable through its web service version. It provides access to ITM Probe either through a web server or locally. The input, consisting of a Cytoscape network, together with the desired origins and/or destinations of information and a dissipation coefficient, is specified through a query form. The results are shown as a subnetwork of significant nodes and several summary tables. Users can control the composition and appearance of the subnetwork and interchange their ITM Probe results with other software tools through tab-delimited files. CONCLUSIONS: The main strength of CytoITMprobe is its flexibility. It allows the user to specify as input any Cytoscape network, rather than being restricted to the pre-compiled protein-protein interaction networks available through the ITM Probe web service. Users may supply their own edge weights and directionalities. Consequently, as opposed to ITM Probe web service, CytoITMprobe can be applied to many other domains of network-based research beyond protein-networks. It also enables seamless integration of ITM Probe results with other Cytoscape plugins having complementary functionality for data analysis.     

widgetcon: A website and program for quick conversion among common population genetic data formats

One of the most tedious steps in genetic data analyses is the reformatting data generated with one program for use with other applications. This conversion is necessary because comprehensive evaluation of the data may be based on different algorithms included in diverse software, each requiring a distinct input format. A platform‐independent and freely available program or a web‐based tool dedicated to such reformatting can save time and efforts in data processing. Here, we report widgetcon , a website and a program which has been developed to quickly and easily convert among various molecular data formats commonly used in phylogenetic analysis, population genetics, and other fields. The web‐based service is available at https://www.widgetcon.net . The program and the website convert the major data formats in four basic steps in less than a minute. The resource will be a useful tool for the research community and can be updated to include more formats and features in the future.     

Yet Another Quick Assembly,Analysis and Trimming Tool (YAQAAT): A Server for the Automated Assembly and Analysis of Sanger Sequencing Data

Even with the ubiquity of Sanger sequencing, automated assembly software are predominantly stand-alone software packages for desktop/laptop use with very few online equivalents, thus geospatially constraining sequence analysis and assembly. With increased data output worldwide, there is also a need for automated quality checks and trimming prior to large assemblies, along with automated detection of mutations. Through web servers with expanded automation and functionalities, even smartphones/phablets can be used to perform complex analysis previously limited to desktops, especially if they can upload files from cloud storage. To facilitate such online accessible sequence assembly and analysis, we created Yet Another Quick Assembly, Analysis and Trimming Tool web server for the automated assembly of multiple .ab1 and .FASTQ sequencing reads de novo with automated trimming and scanning of the assembled sequences for single nucleotide polymorphisms and insertions or deletions without installation of software, allowing it to be accessed from anywhere with Internet access and with minimal dependency on other software and web tools.     

Methods for facilitating web-based participatory research informatics

Scientific datasets are often generated and used by “communities”, or groups of users and creators. These communities, today often virtual, can include researchers, decision-makers, and the general public; participants in these communities may contribute different components during various iterations in the data generation process, and have different needs for resulting data products. As this “participatory research informatics” model, which includes elements of collaborative research, public participation, and digital data libraries, becomes the norm, new approaches to dynamic data management will be important. Researchers commonly use the web as a medium for research collaboration among colleagues, as well as to disseminate results to decision-makers and the public. In addition, the web can be used to facilitate dynamic collaboration by allowing research-in-progress to be accessed and edited by multiple participants. Indeed, one key benefit of using the web to facilitate research projects is that data can undergo revisions and corrections while being displayed in some form over the web. However, it can be a challenge to keep track of multiple edits to files while maintaining the integrity of a web-interface. Here we describe a system for promoting collaboration in the creation, maintenance, and use of dynamic data over the web. Using simple Microsoft Excel spreadsheets combined with traditional relational databases to facilitate dynamic data generation and updates and maintain a data schema, we are able to facilitate efficient collaboration within and among participant communities. This approach allows for the separation of web display and content, which in turn allows participants to be responsible for their own content. This separation simplifies the interaction between those responsible for the content (researchers and other participants), those responsible for the data display (web designers), and those responsible for data management, storage, and retrieval (web programmers). The approach described here is particularly well suited to large, spatially-specific ecological datasets because it can be used to facilitate the “real-time” editing and display of visual data such as web-maps, as well as to encourage multiple participants to both contribute to and interact with “beta” data and content.     

FRETboard: Semisupervised classification of FRET traces

Förster resonance energy transfer (FRET) is a useful phenomenon in biomolecular investigations, as it can be leveraged for nanoscale measurements. The optical signals produced by such experiments can be analyzed by fitting a statistical model. Several software tools exist to fit such models in an unsupervised manner but lack the flexibility to adapt to different experimental setups and require local installations. Here, we propose to fit models to optical signals more intuitively by adopting a semisupervised approach, in which the user interactively guides the model to fit a given data set, and introduce FRETboard, a web tool that allows users to provide such guidance. We show that our approach is able to closely reproduce ground truth FRET statistics in a wide range of simulated single-molecule scenarios and correctly estimate parameters for up to 11 states. On in vitro data, we retrieve parameters identical to those obtained by laborious manual classification in a fraction of the required time. Moreover, we designed FRETboard to be easily extendable to other models, allowing it to adapt to future developments in FRET measurement and analysis.     

Superposition properties of independent ion channels

Membrane patches usually contain several ion channels of a given type. However, most of the stochastic modelling on which data analysis (in particular, estimation of kinetic constants) is currently based, relates to a single channel rather than to multiple channels. Attempts to circumvent this problem experimentally by recording under conditions where channel activity is low are restrictive and can introduce bias; moreover, possibly important information on how multichannel systems behave will be missed. We have extended existing theory to multichannel systems by applying results from point process theory to derive some distributional properties of the various types of sojourn time that occur when a given number of channels are open in a system containing a specified number of independent channels in equilibrium. Separate development of properties of a single channel and the superposition of several such independent channels simplifies the presentation of known results and extensions. To illustrate the general theory, particular attention is given to the types of sojourn time that occur in a two channel system; detailed expressions are presented for a selection of models, both Markov and non-Markov.     

Building protein diagrams on the web with the residue-based diagram editor RbDe

The residue-based diagram editor (RbDe) is web-based software that greatly simplifies the construction of schematic diagrams of proteins. Residue-based diagrams display the sequence of a given protein in the context of its secondary and tertiary structure. Such diagrams are frequently used to summarize mutations or sequence features, in the context of the overall topology of a protein. The initial version of RbDe was designed for transmembrane proteins and has enabled many users to create diagrams of large systems such as G protein-coupled receptors or transporters. We present an extended diagram editor that supports other families of proteins. Users can now import custom-diagram layouts, use them to render members of any protein family and generate high-quality output for publication purposes. RbDe is available free over the web, at http://icb.mssm.edu/crt/RbDe     

High performance web server architecture with Kernel-level caching

In this work we are focusing on reducing response time and bandwidth requirements for high performance web server. Many researches have been done in order to improve web server performance by modifying the web server architecture. In contrast to these approaches, we take a different point of view, in which we consider the web server performance in OS perspective rather than web server architecture itself. To achieve these purposes we are exploring two different approaches. The first is running web server within OS kernel. We use kHTTPd as our basis for implementation. But it has a several drawbacks such as copying data redundantly, synchronous write, and processing only static data. We propose some techniques to improve these flaws. The second approach is caching dynamic data. Dynamic data can seriously reduce the performance of web servers. Caching dynamic data has been thought difficult to cache because it often change a lot more frequently than static pages and because web server needs to access database to provide service with dynamic data. To this end, we propose a solution for higher performance web service by caching dynamic data using content separation between static and dynamic portions. Benchmark results using WebStone show that our architecture can improve server performance by up to 18 percent and can reduce user’s perceived latency significantly.     

Joint modelling of repeated transitions in follow-up data--a case study on breast cancer data

In longitudinal studies where time to a final event is the ultimate outcome often information is available about intermediate events the individuals may experience during the observation period. Even though many extensions of the Cox proportional hazards model have been proposed to model such multivariate time-to-event data these approaches are still very rarely applied to real datasets. The aim of this paper is to illustrate the application of extended Cox models for multiple time-to-event data and to show their implementation in popular statistical software packages. We demonstrate a systematic way of jointly modelling similar or repeated transitions in follow-up data by analysing an event-history dataset consisting of 270 breast cancer patients, that were followed-up for different clinical events during treatment in metastatic disease. First, we show how this methodology can also be applied to non Markovian stochastic processes by representing these processes as "conditional" Markov processes. Secondly, we compare the application of different Cox-related approaches to the breast cancer data by varying their key model components (i.e. analysis time scale, risk set and baseline hazard function). Our study showed that extended Cox models are a powerful tool for analysing complex event history datasets since the approach can address many dynamic data features such as multiple time scales, dynamic risk sets, time-varying covariates, transition by covariate interactions, autoregressive dependence or intra-subject correlation.     

Using Continuous Data Tracking Technology to Study Exercise Adherence in Pulmonary Rehabilitation

Pulmonary rehabilitation (PR) is an important component in the management of respiratory diseases. The effectiveness of PR is dependent upon adherence to exercise training recommendations. The study of exercise adherence is thus a key step towards the optimization of PR programs. To date, mostly indirect measures, such as rates of participation, completion, and attendance, have been used to determine adherence to PR. The purpose of the present protocol is to describe how continuous data tracking technology can be used to measure adherence to a prescribed aerobic training intensity on a second-by-second basis.In our investigations, adherence has been defined as the percent time spent within a specified target heart rate range. As such, using a combination of hardware and software, heart rate is measured, tracked, and recorded during cycling second-by-second for each participant, for each exercise session. Using statistical software, the data is subsequently extracted and analyzed. The same protocol can be applied to determine adherence to other measures of exercise intensity, such as time spent at a specified wattage, level, or speed on the cycle ergometer. Furthermore, the hardware and software is also available to measure adherence to other modes of training, such as the treadmill, elliptical, stepper, and arm ergometer. The present protocol, therefore, has a vast applicability to directly measure adherence to aerobic exercise.