MOTIVATION: Capabilities in the field of metabolomics have grown tremendously in recent years. Many existing resources contain the chemical properties and classifications of commonly identified metabolites. However, the annotation of small molecules (both endogenous and synthetic) to meaningful biological pathways and concepts still lags behind the analytical capabilities and the chemistry-based annotations. Furthermore, no tools are available to visually explore relationships and networks among functionally related groups of metabolites (biomedical concepts). Such a tool would provide the ability to establish testable hypotheses regarding links among metabolic pathways, cellular processes, phenotypes and diseases. RESULTS: Here we present ConceptMetab, an interactive web-based tool for mapping and exploring the relationships among 16 069 biologically defined metabolite sets developed from Gene Ontology, KEGG and Medical Subject Headings, using both KEGG and PubChem compound identifiers, and based on statistical tests for association. We demonstrate the utility of ConceptMetab with multiple scenarios, showing it can be used to identify known and potentially novel relationships among metabolic pathways, cellular processes, phenotypes and diseases, and provides an intuitive interface for linking compounds to their molecular functions and higher level biological effects. AVAILABILITY AND IMPLEMENTATION: http://conceptmetab.med.umich.edu CONTACTS: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Functional enrichment testing facilitates the interpretation of Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data in terms of pathways and other biological contexts. Previous methods developed and used to test for key gene sets affected in ChIP-seq experiments treat peaks as points, and are based on the number of peaks associated with a gene or a binary score for each gene. These approaches work well for transcription factors, but histone modifications often occur over broad domains, and across multiple genes. RESULTS: To incorporate the unique properties of broad domains into functional enrichment testing, we developed Broad-Enrich, a method that uses the proportion of each gene's locus covered by a peak. We show that our method has a well-calibrated false-positive rate, performing well with ChIP-seq data having broad domains compared with alternative approaches. We illustrate Broad-Enrich with 55 ENCODE ChIP-seq datasets using different methods to define gene loci. Broad-Enrich can also be applied to other datasets consisting of broad genomic domains such as copy number variations. AVAILABILITY AND IMPLEMENTATION: http://broad-enrich.med.umich.edu for Web version and R package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: In recent years, metabolomics has emerged as an approach to perform large-scale characterization of small molecules in biological systems. Metabolomics posed a number of bioinformatics challenges associated in data analysis and interpretation. Genome-based metabolic reconstructions have established a powerful framework for connecting metabolites to genes through metabolic reactions and enzymes that catalyze them. Pathway databases and bioinformatics tools that use this framework have proven to be useful for annotating experimental metabolomics data. This framework can be used to infer connections between metabolites and diseases through annotated disease genes. However, only about half of experimentally detected metabolites can be mapped to canonical metabolic pathways. We present a new Cytoscape 3 plug-in, MetDisease, which uses an alternative approach to link metabolites to disease information. MetDisease uses Medical Subject Headings (MeSH) disease terms mapped to PubChem compounds through literature to annotate compound networks. AVAILABILITY AND IMPLEMENTATION: MetDisease can be downloaded from http://apps.cytoscape.org/apps/metdisease or installed via the Cytoscape app manager. Further information about MetDisease can be found at http://metdisease.ncibi.org CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary Data are available at Bioinformatics online.

MOTIVATION: Metabolomics is a rapidly evolving field that holds promise to provide insights into genotype-phenotype relationships in cancers, diabetes and other complex diseases. One of the major informatics challenges is providing tools that link metabolite data with other types of high-throughput molecular data (e.g. transcriptomics, proteomics), and incorporate prior knowledge of pathways and molecular interactions. RESULTS: We describe a new, substantially redesigned version of our tool Metscape that allows users to enter experimental data for metabolites, genes and pathways and display them in the context of relevant metabolic networks. Metscape 2 uses an internal relational database that integrates data from KEGG and EHMN databases. The new version of the tool allows users to identify enriched pathways from expression profiling data, build and analyze the networks of genes and metabolites, and visualize changes in the gene/metabolite data. We demonstrate the applications of Metscape to annotate molecular pathways for human and mouse metabolites implicated in the pathogenesis of sepsis-induced acute lung injury, for the analysis of gene expression and metabolite data from pancreatic ductal adenocarcinoma, and for identification of the candidate metabolites involved in cancer and inflammation. AVAILABILITY: Metscape is part of the National Institutes of Health-supported National Center for Integrative Biomedical Informatics (NCIBI) suite of tools, freely available at http://metscape.ncibi.org. It can be downloaded from http://cytoscape.org or installed via Cytoscape plugin manager. CONTACT: [email protected]; [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Metscape is a plug-in for Cytoscape, used to visualize and interpret metabolomic data in the context of human metabolic networks. We have developed a metabolite database by extracting and integrating information from several public sources. By querying this database, Metscape allows users to trace the connections between metabolites and genes, visualize compound networks and display compound structures as well as information for reactions, enzymes, genes and pathways. Applying the pathway filter, users can create subnetworks that consist of compounds and reactions from a given pathway. Metscape allows users to upload experimental data, and visualize and explore compound networks over time, or experimental conditions. Color and size of the nodes are used to visualize these dynamic changes. Metscape can display the entire metabolic network or any of the pathway-specific networks that exist in the database. AVAILABILITY: Metscape can be installed from within Cytoscape 2.6.x under 'Network and Attribute I/O' category. For more information, please visit http://metscape.ncibi.org/tryplugin.html.

Abstract Motivation: The elucidation of biological concepts enriched with differentially expressed genes has become an integral part of the analysis and interpretation of genomic data. Of additional importance is the ability to explore networks of relationships among previously defined biological concepts from diverse information sources, and to explore results visually from multiple perspectives. Accomplishing these tasks requires a unified framework for agglomeration of data from various genomic resources, novel visualizations, and user functionality. Results: We have developed ConceptGen, a web-based gene set enrichment and gene set relation mapping tool that is streamlined and simple to use. ConceptGen offers over 20 000 concepts comprising 14 different types of biological knowledge, including data not currently available in any other gene set enrichment or gene set relation mapping tool. We demonstrate the functionalities of ConceptGen using gene expression data modeling TGF-beta-induced epithelial-mesenchymal transition and metabolomics data comparing metastatic versus localized prostate cancers. Availability: ConceptGen is part of the NIH's National Center for Integrative Biomedical Informatics (NCIBI) and is freely available at http://conceptgen.ncibi.org. For terms of use, visit http://portal.ncibi.org/gateway/pdf/Terms%20of%20use-web.pdf Contact: [email protected]; [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

UNLABELLED: The MiMI molecular interaction repository integrates data from multiple sources, resolves interactions to standard gene names and symbols, links to annotation data from GO, MeSH and PubMed and normalizes the descriptions of interaction type. Here, we describe a Cytoscape plugin that retrieves interaction and annotation data from MiMI and links out to multiple data sources and tools. Community annotation of the interactome is supported. AVAILABILITY: MiMI plugin v3.0.1 can be installed from within Cytoscape 2.6 using the Cytoscape plugin manager in 'Network and Attribute I/0' category. The plugin is also preloaded when Cytoscape is launched using Java WebStart at http://mimi.ncibi.org by querying a gene and clicking 'View in MiMI Plugin for Cytoscape' link.

Autonomous robot navigation requires the solution of several problems like obstacle avoidance and road following. Traditionally, the problem of obstacle avoidance has been solved by using range information acquired through some form of range measurements like laser range cameras or vision based range estimation. This paper presents a novel approach for obstacle avoidance which does not require true range measurement. Obstacle information is acquired using a single color camera. Detected obstacles are projected into 3D grid derived from the camera geometry and a locally flat earth model for the terrain. A weighted polar histogram technique is used to generate the vehicle steering angle based on the current grid information.>

The data driven, bottom up approach to video segmentation has ignored the inherent structure that exists in video. This work uses the model driven approach to digital video segmentation. Mathematical models of video based on video production techniques are formulated. These models are used to classify the edit effects used in video and film production. The classes and models are used to systematically design the feature detectors for detecting edit effects in digital video. Digital video segmentation is formulated as a feature based classification problem. Experimental results from segmenting cable television programming with cuts, fades, dissolves and page translate edits are presented.

An abstraction-based paradigm that makes explicit the process of imposing assumptions on data is discussed. The units of abstraction are models in which levels of abstraction are determined by the degree of assumption necessary for their application. A general-to-specific refinement process provides a mechanism to proceed gracefully through the abstraction hierarchy. This strategy was applied to the recognition and pose determination of objects comprising simple and compound cylindrical and planar surfaces in dense range data. A method of computing reliable Gaussian and mean curvature sign-map descriptors from the polynomial approximations of surfaces is demonstrated. A means for determining the pose of constructed geometric forms whose algebraic surface descriptions are nonlinear in terms of their orienting parameters is developed. It is shown that biquadratic surfaces are suitable companion-linear forms for cylinder approximation and parameter estimation. The estimates provide the initial parametric approximations necessary for a nonlinear regression stage to fine tune the estimates by fitting the actual nonlinear form to the data.>

The authors present a novel approach to the problem of constructing a depth map from a sequence of monocular images. The approach requires knowledge only of the axial translation component of the moving camera. When the configuration of the camera is known with respect to the mobile platform, this information can be readily obtained by projecting displacement data from a wheel encoder or range sensors onto the focal axis. It is hypothesized that there is a pair of feature points which have the same depth. Based on this hypothesis, the depths are calculated for all pairs of feature points found in the image. As the robot moves, the relative location of two points changes in a specific and predictable manner on the image plane if they are actually at the same depth. The motion of each pair of points is observed, and if it is consistent with the predicted behavior, the hypothesis is accepted. Accepted pairs create a graph structure which contains depth relations among the feature points. The algorithm is robust against rotational and translational motion noises, and its performance has been experimentally demonstrated.>

Pose determination for robot navigation is discussed. The problem is to maintain the system's instantaneous precept of its position and orientation in space for performing various tasks. The authors describe a system in which models were used to guide the sensory interpretation and to correct expectations. In this system, simulated images were used to analyze the real images and to correct the pose parameters. The reported techniques have been implemented and experiments with real images in a real environment have been performed.>

The infrared (IR) range sensors currently mounted on a mobile pllatform in the Mobile Robot Laboratory at the University of Michigan have a limited range resolution due to their 4 bit analog-to- digital converter (ADC). However, it is possible to obtain better resolution without changing the current hardware configuration by using knowledge about the robot's motion. This paper presents the algorithm for IR range estimation with sub-step accuracy. As the robot moves, a transition monitor detects the instance that a trimmed mean of the IR sensor outputs changes from one ADC step to another and evaluates the importance of the data depending on the type of transition. The information from the transition monitor is integrated recursively in time with the displacement information from an encoder to give the qub-step accuracy in the range estimates. Our algorithm also provides an improved range estimate error bound which is useful in sensor fusion and other applications. Details of the transition monitor are described in this paper, and experimental results which demonstrated a successful implementation of the algorithm are presented. The idea behind the algorithm can be applied to other sensor modalities having resolution primarily limited by a digitization device.

The authors show how stereo-based range data, obtained over time by a moving vehicle can be integrated without the explicit knowledge or computation of camera motion. A unique aspect of the approach is the transformation of range information into relative distances and encoding these distances in image registered maps. Results of experiments on dynamic stereo images, are presented.>

It is shown how a contour can be estimated from a few edge positions. The technique fits a cubic spline to edges using the position and orientations of edges (tangent slopes) and computes tangent magnitudes by a minimization based on the second derivatives. Cubic splines (piecewise third-order polynomials) are used because they are the lowest-order polynomials that can deal with inflection points. For assuring a smooth overall contour, the polynomial segments are joined such that the continuity of the first derivative is preserved and discontinuity in the second derivative is minimized. This technique can be used as an efficient means for entering and editing contours which are tied to the underlying data through the edge orientations. The time required for computing the edge orientations and the time for finding the curve parameters are linearly proportional to the number of edge fragments. The algorithm was applied to medical images, and the results are compared with the conic splines and the B-splines and the distance approximation to the cubic splines.>

Fusion of 3-D spatial information obtained by a dynamic vision system is addressed. The representation of information is seen to be critical in forming a solution. An object-centered representation that encodes, in image registered maps, the relative distances of objects to a set of scene referents is proposed. This representation facilitates fusion of dynamic spatial information without direct use or knowledge of camera motion and points the way for a new model for dynamic vision.>

Dynamic programming is discussed as an approach to solving variational problems in vision. Dynamic programming ensures global optimality of the solution, is numerically stable, and allows for hard constraints to be enforced on the behavior of the solution within a natural and straightforward structure. As a specific example of the approach's efficacy, applying dynamic programming to the energy-minimizing active contours is described. The optimization problem is set up as a discrete multistage decision process and is solved by a time-delayed discrete dynamic programming algorithm. A parallel procedure for decreasing computational costs is discussed.>

A novel depth computation algorithm is described. Based on linear equations derived from the consideration of relative normal velocity, this algorithm determines depth values locally and uniquely from normal velocities. Multiple independently moving objects present no problem for the algorithm. A velocity constraint is implemented to estimate normal velocities from intensity images. Experiments to determine depth values from both synthetic images and real images are presented. The experiments show that the depth-recovery algorithm can recover correct values from intensity images. The accuracy of the depth values depends heavily on the accuracy of the normal velocities.>

Interpolation of X-ray motion pictures of the heart (cineventiculograms of the left ventricle) is complicated by the low contrast of the images and the elastic motion of the heart. Here, the problem of placing the heart boundary in each frame of the motion sequence is described by a framework for the application of knowledge in the form of diagnostically relevant models of the heart in motion. A blackboard architecture is utilized as a basis for the image interpretation. In this architecture, local features such as edges are grouped to build a complete description of the moving heart; the knowledge is organized in a hierarchy with knowledge sources (KSs) operating on different levels of the hierarchy and opportunistic problem-solving techniques are used to control the order of activation of both data-directed and goal-driven sources.>

Stereo algorithms using a wide baseline must cope with a large search space on top of the problems due to noise. A single pair of images is not a reliable source of depth information. One solution is to integrate the information from several image pairs. By incrementally refining estimates of the depth as the camera changes position, it is possible to build a description of the scene which, in turn, can be used as feedback to improve the extraction of depth information. The authors have developed a stereo algorithm based on correlation matching that is especially suited to being integrated into a proposed feedback loop. They have begun experiments with the integration of depth information over a sequence into a single environmental map.>

Energy-Minimizing Active Contour Models (snakes) have recently been proposed by Kass et al. [8] as a top-down mechanism for locating features of interest in images. The Kass et al.’s algorithm involves four steps: setting up a variational integral on the continuous plane, deriving a pair of Euler equations, discretizing them, and solving the discrete equations iteratively until convergence. This algorithm suffers from a number of problems. We discuss these problems and present an algoIithm for active contours based on dynamic programming. The optimization problem is set up as a discrete multi-stage decision process and is solved by a “time-delayed” discrete dynamic programming algorithm. This formulation leads to a stable behavior for the active contours over iterations, in addition to allowing for hard constraints to be enforced on the behavior of the solution. Results of the application of the proposed algorithm to real images is presented.

Described in this paper is a small, modular operating system which was written for an Interdata-70 machine, Tbe total operating system is memory resident and occupies 5K bytes.The primary motivation in redesigning the operating system was to structure it so that students and general system users could easily expand or modify the basic services of the supervising system.Towards this end, the following system principles are embodied in the design:(i) clearly defined separation of system functions, (2) separate object modules for each system routine, and (3) simple system design.Although specifics of implementation are discussed, general design concepts are covered which should aid the reader in any similar attempt (either by example or counter example).

This paper describes the use of the Chief Programmer Team method in an operating systems class to implement a subset of a multiprogramming operating system. The operating system consisted of elements of Job Management, Task Management, and Data Management functions. The students were divided into four groups. One of these, called the Steering Committee, was responsible for assigning coding and design duties to each of the three coding groups. When each major part of the operating system was completed, the Steering Committee would examine the code and approve it, or return it to the coding group for revision. Thus, the Steering Committee acted as Chief Programmer to the other three groups. When all parts of the system were completed, they were linked together and tested. A comprehensive survey containing questions regarding the effectiveness of the Chief Programmer approach was given to all students. The results of this survey indicated that the group programming effort was superior to the conventional method of assigning the project, in its entirety, to each student. Key Words: Chief Programmer Team, Monitor, Operating Systems, Systems Programming.