GeneWiz browser: An Interactive Tool for Visualizing Sequenced Chromosomes

We present an interactive web application for visualizing genomic data of prokaryotic chromosomes. The tool (GeneWiz browser) allows users to carry out various analyses such as mapping alignments of homologous genes to other genomes, mapping of short sequencing reads to a reference chromosome, and calculating DNA properties such as curvature or stacking energy along the chromosome. The GeneWiz browser produces an interactive graphic that enables zooming from a global scale down to single nucleotides, without changing the size of the plot. Its ability to disproportionally zoom provides optimal readability and increased functionality compared to other browsers. The tool allows the user to select the display of various genomic features, color setting and data ranges. Custom numerical data can be added to the plot allowing, for example, visualization of gene expression and regulation data. Further, standard atlases are pre-generated for all prokaryotic genomes available in GenBank, providing a fast overview of all available genomes, including recently deposited genome sequences. The tool is available online from http://www.cbs.dtu.dk/services/gwBrowser. Supplemental material including interactive atlases is available online at http://www.cbs.dtu.dk/services/gwBrowser/suppl/.     

FTSPlot: Fast Time Series Visualization for Large Datasets

The analysis of electrophysiological recordings often involves visual inspection of time series data to locate specific experiment epochs, mask artifacts, and verify the results of signal processing steps, such as filtering or spike detection. Long-term experiments with continuous data acquisition generate large amounts of data. Rapid browsing through these massive datasets poses a challenge to conventional data plotting software because the plotting time increases proportionately to the increase in the volume of data. This paper presents FTSPlot, which is a visualization concept for large-scale time series datasets using techniques from the field of high performance computer graphics, such as hierarchic level of detail and out-of-core data handling. In a preprocessing step, time series data, event, and interval annotations are converted into an optimized data format, which then permits fast, interactive visualization. The preprocessing step has a computational complexity of ; the visualization itself can be done with a complexity of and is therefore independent of the amount of data. A demonstration prototype has been implemented and benchmarks show that the technology is capable of displaying large amounts of time series data, event, and interval annotations lag-free with ms. The current 64-bit implementation theoretically supports datasets with up to bytes, on the x86_64 architecture currently up to bytes are supported, and benchmarks have been conducted with bytes/1 TiB or double precision samples. The presented software is freely available and can be included as a Qt GUI component in future software projects, providing a standard visualization method for long-term electrophysiological experiments.     

Mapping sequenced E.coli genes by computer: software, strategies and examples.

Methods are presented for organizing and integrating DNA sequence data, restriction maps, and genetic maps for the same organism but from a variety of sources (databases, publications, personal communications). Proper software tools are essential for successful organization of such diverse data into an ordered, cohesive body of information, and a suite of novel software to support this endeavor is described. Though these tools automate much of the task, a variety of strategies is needed to cope with recalcitrant cases. We describe such strategies and illustrate their application with numerous examples. These strategies have allowed us to order, analyze, and display over one megabase of E. coli DNA sequence information. The integration task often exposes inconsistencies in the available data, perhaps caused by strain polymorphisms or human oversight, necessitating the application of sound biological judgment. The examples illustrate both the level of expertise required of the database curator and the knowledge gained as apparent inconsistencies are resolved. The software and mapping methods are applicable to the study of any genome for which a high resolution restriction map is available. They were developed to support a weakly coordinated sequencing effort involving many laboratories, but would also be useful for highly orchestrated sequencing projects.     

Automatic analysis of agarose gel images.

MOTIVATION: Automatic tools to speed up routine biological processes are very much sought after in bio-medical research. Much repetitive work in molecular biology, such as allele calling in genetic analysis, can be made semi-automatic or task specific automatic by using existing techniques from computer science and signal processing. Computerized analysis is reproducible and avoids various forms of human error. Semi-automatic techniques with an interactive check on the results speed up the analysis and reduce the error. RESULTS: We have successfully implemented an image processing software package to automatically analyze agarose gel images of polymorphic DNA markers. We have obtained up to 90% accuracy for the classification of alleles in good quality images and up to 70% accuracy in average quality images. These results are obtained within a few seconds. Even after subsequent interactive checking to increase the accuracy of allele classification to 100%, the overall speed with which the data can be processed is greatly increased, compared to manual allele classification. AVAILABILITY: The IDL source code of the software is available on request from jonathan.flint@well.ox.ac.uk     

Automated band mapping in electrophoretic gel images using background information

Some popular methods for polymorphism and mutation discovery involve ascertainment of novel bands by the examination of electrophoretic gel images. Although existing strategies for mapping bands work well for specific applications, such as DNA sequencing, these strategies are not well suited for novel band detection. Here, we describe a general strategy for band mapping that uses background banding patterns to facilitate lane calling and size calibration. We have implemented this strategy in GelBuddy, a user-friendly Java-based program for PC and Macintosh computers, which includes several utilities to assist discovery of mutations and polymorphisms. We demonstrate the use of GelBuddy in applications based on single-base mismatch cleavage of heteroduplexed PCR products. Use of software designed to facilitate novel band detection can significantly shorten the time needed for image analysis and data entry in a high-throughput setting. Furthermore, the interactive strategy implemented in GelBuddy has been successfully applied to DNA fingerprinting applications, such as AFLP. GelBuddy promises to make electrophoretic gel analysis a viable alternative to DNA resequencing for discovery of mutations and polymorphisms.     

JDotter: a Java interface to multiple dotplots generated by dotter

Java-Dotter (JDotter) is a platform-independent Java interactive interface for the Linux version of Dotter, a widely used program for generating dotplots of large DNA or protein sequences. JDotter runs as a client-server application and can send new sequences to the Dotter program for alignment as well as rapidly access a repository of preprocessed dotplots. JDotter also interfaces with a sequence database or file system to display supplementary feature data. Thus, JDotter greatly simplifies access to dotplot data in laboratories that deal with large numbers of genomes and have a multi-platform organization. AVAILABILITY: Currently, JDotter is used via Java Web Start by the Poxvirus Bioinformatics Resource for examining dotplots of complete poxvirus genomes; http://athena.bioc.uvic.ca/pbr/jdotter/. The software is available for download from the same location. SUPPLEMENTARY INFORMATION: Installation instructions, the User's Manual, screenshots and examples are available at the JDotter home page http://athena.bioc.uvic.ca/pbr/jdotter/. The software and source code is free for non-commercial applications.     

shinyChromosome:An R/Shiny Application for Interactive Creation of Non-circular Plots of Whole Genomes

Non-circular plots of whole genomes are natural representations of genomic data aligned along all chromosomes.Currently,there is no specialized graphical user interface(GUI) designed to produce non-circular whole genome diagrams,and the use of existing tools requires considerable coding effort from users.Moreover,such tools also require improvement,including the addition of new functionalities.To address these issues,we developed a new R/Shiny application,named shiny Chromosome,as a GUI for the interactive creation of non-circular whole genome diagrams.shiny Chromosome can be easily installed on personal computers for own use as well as on local or public servers for community use.Publication-quality images can be readily generated and annotated from user input using diverse widgets.shiny Chromosome is deployed at http://150.109.59.144:3838/shiny Chromosome/,http://shiny Chromosome.ncpgr.cn,and https://yimingyu.shinyapps.io/shiny Chromosome for online use.The source code and manual of shiny Chromosome are freely available at https://github.com/venyao/shiny Chromosome.     

An affordable approach to interactive desktop molecular modeling

The amazing revolution in computer hardware performance and cost reduction has yet to be carried over to computer software. In fact, application software today is often more expensive and less reliable than the hardware. New enhancements in software development techniques, such as object oriented programming and interactive graphics based user interface design, finally may be having a significant impact on the time-to-market and reliability of these application programs. We discuss our experiences using one such set of software development tools available on the NeXT workstation and describe the effort required to port our MidasPlus molecular modeling package to the NeXT workstation.     

Acquiring Fluorescence Time-lapse Movies of Budding Yeast and Analyzing Single-cell Dynamics using GRAFTS

Fluorescence time-lapse microscopy has become a powerful tool in the study of many biological processes at the single-cell level. In particular, movies depicting the temporal dependence of gene expression provide insight into the dynamics of its regulation; however, there are many technical challenges to obtaining and analyzing fluorescence movies of single cells. We describe here a simple protocol using a commercially available microfluidic culture device to generate such data, and a MATLAB-based, graphical user interface (GUI) -based software package to quantify the fluorescence images. The software segments and tracks cells, enables the user to visually curate errors in the data, and automatically assigns lineage and division times. The GUI further analyzes the time series to produce whole cell traces as well as their first and second time derivatives. While the software was designed for S. cerevisiae, its modularity and versatility should allow it to serve as a platform for studying other cell types with few modifications.     

The expert teaching system: a new method for learning rhinoplasty using interactive computer graphics

We have developed software that employs interactive computer graphics to simulate the surgical experience of rhinoplasty by allowing the surgeon to experiment within a model of nasal behavior. For any of three preoperative noses, the surgeon can choose and see the effects of dorsal resection, modification of nasal spine or caudal septum, alar cartilage resection, osteotomy, alar wedge resection, and a variety of nasal grafts. The available choices and views total nearly 3000 images, or approximately 200 different surgical solutions. The surgeon can get textual analysis at any time or see accelerated healing to the projected nasal appearance at 1 year. We believe that the ability to experiment without risk, to safely learn the biological laws governing nasal behavior, should augment the development of surgical judgement in rhinoplasty.     

MOLECULAR DESIGNER: an interactive program for the display of protein structure on the IBM-PC

A BASIC interactive graphics program has been developed forthe IBM-PC which utilizes the graphics capabilities of thatcomputer to display and manipulate protein structure from coordinates.Structures may be generated from typed files, or from BrookhavenNational Laboratories' Protein Data Bank data tapes. Once displayed,images may be rotated, translated and expanded to any desiredsize. Figures may be viewed as ball-and-stick or space-fillingmodels. Calculated multiple-point perspective may also be addedto the display. Docking manipulations are possible since morethan a single figure may be displayed and manipulated simultaneously.Further, stereo images and red/blue three-dimensional imagesmay be generated using the accompanying DESIPLOT program andan HP-7475A plotter. A version of the program is also currentlyavailable for the Apple Macintosh. Full implementation on theMacintosh requires 512 K and at least one disk drive. Otherwisethis version is essentially identical to the IBM-PC versiondescribed herein. Received on July 12, 1985; accepted on August 1, 1985     

Using Sculptor and Situs for simultaneous assembly of atomic components into low-resolution shapes

We describe an integrated software system called Sculptor that combines visualization capabilities with molecular modeling algorithms for the analysis of multi-scale data sets. Sculptor features extensive special purpose visualization techniques that are based on modern GPU programming and are capable of representing complex molecular assemblies in real-time. The integration of graphics and modeling offers several advantages. The user interface not only eases the usually steep learning curve of pure algorithmic techniques, but it also permits instant analysis and post-processing of results, as well as the integration of results from external software. Here, we implemented an interactive peak-selection strategy that enables the user to explore a preliminary score landscape generated by the colors tool of Situs. The interactive placement of components, one at a time, is advantageous for low-resolution or ambiguously shaped maps, which are sometimes difficult to interpret by the fully automatic peak selection of colors. For the subsequent refinement of the preliminary models resulting from both interactive and automatic peak selection, we have implemented a novel simultaneous multi-body docking in Sculptor and Situs that softly enforces shape complementarities between components using the normalization of the cross-correlation coefficient. The proposed techniques are freely available in Situs version 2.6 and Sculptor version 2.0.     

TOPALi: software for automatic identification of recombinant sequences within DNA multiple alignments

SUMMARY: TOPALi is a new Java graphical analysis application that allows the user to identify recombinant sequences within a DNA multiple alignment (either automatically or via manual investigation). TOPALi allows a choice of three statistical methods to predict the positions of breakpoints due to past recombination. The breakpoint predictions are then used to identify putative recombinant sequences and their relationships to other sequences. In addition to its sophisticated interface, TOPALi can import many sequence formats, estimate and display phylogenetic trees and allow interactive analysis and/or automatic HTML report generation. AVAILABILITY: TOPALi is freely available from http://www.bioss.ac.uk/software.html     

Principles of electroanatomic mapping

Electrophysiologic testing and radiofrequency ablation have evolved as curative measures for a variety of rhythm disturbances. As experience in this field has grown, ablation is progressively being used to address more complex rhythm disturbances. Paralleling this trend are technological advancements to facilitate these efforts, including electroanatomic mapping (EAM). At present, several different EAM systems utilizing various technologies are available to facilitate mapping and ablation. Use of these systems has been shown to reduce fluoroscopic exposure and radiation dose, with less significant effects on procedural duration and success rates. Among the data provided by EAM are chamber reconstruction, tagging of important anatomic landmarks and ablation lesions, display of diagnostic and mapping catheters without using fluoroscopy, activation mapping, and voltage (or scar) mapping. Several EAM systems have specialized features, such as enhanced ability to map non-sustained or hemodynamically unstable arrhythmias, ability to display diagnostic as well as mapping catheter positions, and wide compatibility with a variety of catheters. Each EAM system has its strengths and weaknesses, and the system chosen must depend upon what data is required for procedural success (activation mapping, substrate mapping, cardiac geometry), the anticipated arrhythmia, the compatibility of the system with adjunctive tools (i.e. diagnostic and ablation catheters), and the operator's familiarity with the selected system. While EAM can offer significant assistance during an EP procedure, their incorrect or inappropriate application can substantially hamper mapping efforts and procedural success, and should not replace careful interpretation of data and strict adherence to electrophysiologic principles.     

ChromoScan: a scan statistic application for identifying chromosomal regions in genomic studies

ChromoScan is an implementation of a genome-based scan statistic that detects genomic regions, which are statistically significant for targeted measurements, such as genetic associations with disease, gene expression profiles, DNA copy number variations, as well as other genome-based measurements. A Java graphic user interface (GUI) is provided to allow users to select appropriate data transformations and thresholds for defining the significant events. AVAILABILITY: ChromoScan is freely available from http://www.epidkardia.sph.umich.edu/software/chromoscan/     

Texture mapping: A new tool for molecular graphics

The real-time texture mapping capabilities of modern graphics workstations are explored with respect to their applications in a variety of relevant scenarios in interactive molecular modeling techniques. The common usage of texture mapping to reduce geometric complexity while enhancing realism is extended, opening new ways to visualize large amounts of molecular data in a comprehensive fashion. Thus, texture mapping may be employed to (1) display and filter multichannel information of structural properties on molecular surfaces, (2) improve the quality and accuracy of highly complex isodensity contours, (3) increase the rendering speed of space-filling atomic representations by two orders of magnitude and (4) apply volume-rendering techniques to large, three-dimensional density distributions in real time. Implementation of these novel techniques requires only moderate modifications or extensions to existing molecular modeling applications.     

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.     

Photorealistic image generation of molecular structure on PC screen using the ray-tracing technique

A PC version of three-dimensional molecular graphics package has been developed to run under MS-DOS environment on IBM PC-compatible computers equipped with a VGA graphics board. The program consists of two parts: a menu-driven interactive system module in EGA mode, and a ray-tracing module in VGA mode. In the 256-color VGA mode, ray-tracing images are represented with a 4-color map, with 64 levels for each color: 32 levels of illuminance and 32 levels of saturation. Molecular structure can be analyzed along various directions with various light sources. Ray-tracing images are also represented in a 16-color EGA mode with the half-toning method, which can display 76 gray levels for each color. To obtain good photo-realistic images in an efficient way, we have used two light sources, with an intensity ratio of 7:3, which are located in front of the top right and bottom left corners of the screen.