Data mining the zebrafish genome.
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In the past decade, the scientific community has realized the value of three-dimensional (3D) structural information and '3D searching' has started to become an important new methodology for computer-aided drug design. During this time, molecular modeling information generated from various sources has proliferated due to the growing availability of software and hardware and the increasing use of crystallographic and spectroscopic techniques. This information needs to be organized to allow for its effective storage and retrieval. This paper presents an approach to address this problem with a recently introduced program, MACCS-3D. In particular, this approach utilizes MACCS-3D's capability of handling data specific for atoms and atom pairs. With this software, various biological, computational, and spectroscopic data can be merged, allowing scientists from different disciplines to access and use this information more efficiently.
As the number and diversity of contributions to the medical literature continue to grow at an astronomic rate, vascular surgeons are feeling increasingly frustrated in their efforts to remain current with the latest developments in their specialty. The introduction of powerful, inexpensive microcomputers and "user-friendly" programs for data base management has made it possible to organize large amounts of information for subsequent review. Using such a microcomputer-based system, we developed a practical approach to the storage and retrieval of vascular surgical references, which permits virtually unlimited numbers of articles to be catalogued and quickly retrieved with multiple search parameters. This system has been operational in our Division of Vascular Surgery for nearly a year and currently contains more than 3000 journal articles that are readily available for resident teaching, patient care, and research.
In 1997 an internally supported but unfunded pilot project at the Victorian Institute of Forensic Medicine (VIFM) Australia led to the development of a computer system which closely mimicked Interpol paperwork for the storage, later retrieval and tentative matching of the many AM and PM dental records that are often needed for rapid Disaster Victim Identification. The program was called "DAVID" (Disaster And Victim IDentification). It combined the skills of the VIFM Information Technology systems manager (VW), an experienced odontologist (JGC) and an expert database designer (JC); all current authors on this paper. Students did much of the writing of software to prescription from Monash University. The student group involved won an Australian Information Industry Award in recognition of the contribution the new software could have made to the DVI process. Unfortunately, the potential of the software was never realized because paradoxically the federal nature of Australia frequently thwarts uniformity of systems across the entire country. As a consequence, the final development of DAVID never took place. Given the recent problems encountered post-tsunami by the odontologists who were obliged to use the Plass Data system (Plass Data Software, Holbaek, Denmark) and with the impending risks imposed upon Victoria by the decision to host the Commonwealth Games in Melbourne during March 2006, funding was sought and obtained from the state government to update counter disaster preparedness at the VIFM. Some of these funds have been made available to upgrade and complete the DAVID project. In the wake of discussions between leading expert odontologists from around the world held in Geneva during July 2003 at the invitation of the International Committee of the Red Cross significant alterations to the initial design parameters of DAVID were proposed. This was part of broader discussions directed towards developing instruments which could be used by the ICRC's "The Missing" project that seeks to identify the victims of civil unrest and other atrocities. The most significant of these recommendations was that the next version of DAVID should be web-based allowing it to be used anywhere in the world and on any computer platform. The original intention that the software should be made available as freeware was strongly reiterated and endorsed. During 2005 these recommendations have been realized. This paper will describe the design parameters of the new software "DAVID web" and compare its features and performance with alternative packages.
Medical data are characterized by complex taxonomies and evolving terminology. Questions that clinicians, medical administrators, and researchers may wish to answer using medical databases are not easily formulated as SQL queries. In this paper we describe a graphical tool that facilitates formulation of ad hoc questions as SQL queries. This tool manages multiple attribute hierarchies and creates SQL query strings by navigating through the hierarchies. This interactive tool has been optimized using indexing to improve the overall speed of the query building and the data retrieval process. Indexed queries performed 5 to 100 times faster than query strings. However, query string generation time depends on the size of the taxonomies describing the hierarchies, while the index generation time depends on the size of the data warehouse.
A project to recatalog and reclassify the book collection of the Bowman Gray School of Medicine Library utilizing the Magnetic Tape/Selectric Typwriter system for simultaneous catalog card production and computer stored data acquisition marks the beginning of eventual computerization of all library operations. A keyboard optical display system will be added by late 1970. Major input operations requiring the creation of "hard copy" will continue via the MTST system. Updating, editing and retrieval operations as well as input without hard copy production will be done through the "on-line" keyboard optical display system. Once the library's first data bank, the book catalog, has been established the computer may be consulted directly for library holdings from any optical display terminal throughout the medical center. Three basic information retrieval operations may be carried out through "on-line" optical display terminals. Output options include the reproduction of part or all of a given document, or the generation of statistical data, which are derived from two Acquisition Code lines. The creation of a central bibliographic record of Bowman Gray Faculty publications patterned after the cataloging program is presently under way. The cataloging and computer storage of serial holdings records will begin after completion of the reclassification project. All acquisitions added to the collection since October 1967 are computer-stored and fully retrievable. Reclassification of older titles will be completed in early 1971.
In spite of the acknowledged role that the thalamus plays in declarative memory, details about the precise memory processes it is involved in and which are the structures of the thalamus that contribute to these processes remain unknown. An overview is presented of human clinical and animal experimental findings showing the involvement of the thalamus, at the level of white matter tracts and separate nuclei, in aspects of memory functioning. The region in the thalamus that contributes to declarative memory is the anterior and medial division, containing the anterior nuclei, the medial dorsal nucleus and the intralaminar and midline nuclei. A lesion to the anterior nuclei or their afferent white matter tract, the mammillothalamic tract, results in deficits of encoding of new stimuli. Lesions to the medial dorsal nucleus affect executive processes pertaining to declarative memory, such as the use of memory strategies for retrieval; damage to the intralaminar and midline nuclei results in decreased arousal and thus affects the declarative memory process. Based on anatomical and functional data, a theory is proposed of how the thalamus might play a role at different levels of declarative memory functioning. Firstly, the anterior and mediodorsal nucleus are involved in processing the contents of the stimuli for storage and recall. The anterior nuclei influence the selection of material to be stored and remembered, whereas the mediodorsal nucleus is involved in the coordination and selection of the strategies used to retrieve material. Secondly, the intralaminar and midline nuclei and specifically the lateral and ventral components, maintain a necessary state of the cortical regions involved in the ongoing memory processes. The two types of function subserved by these groups of thalamic nuclei, focussing on contents vs. state, need to work in parallel to mediate and allow memory functioning, respectively.
A powerful method of processing MEDLINE and CINAHL source data uploaded to the IBM 3090 mainframe computer through an IBM/PC is described. Data are first downloaded from the CD-ROM's PC devices to floppy disks. These disks then are uploaded to the mainframe computer through an IBM/PC equipped with WordPerfect text editor and computer network connection (SONNGATE). Before downloading, keywords specifying the information to be accessed are typed at the FIND prompt of the CD-ROM station. The resulting abstracts are downloaded into a file called DOWNLOAD.DOC. The floppy disks containing the information are simply carried to an IBM/PC which has a terminal emulation (TELNET) connection to the university-wide computer network (SONNET) at the Ohio State University Academic Computing Services (OSU ACS). The WordPerfect (5.1) processes and saves the text into DOS format. Using the File Transfer Protocol (FTP, 130,000 bytes/s) of SONNET, the entire text containing the information obtained through the MEDLINE and CINAHL search is transferred to the remote mainframe computer for further processing. At this point, abstracts in the specified area are ready for immediate access and multiple retrieval by any PC having network switch or dial-in connection after the USER ID, PASSWORD and ACCOUNT NUMBER are specified by the user. The system provides the user an on-line, very powerful and quick method of searching for words specifying: diseases, agents, experimental methods, animals, authors, and journals in the research area downloaded. The user can also copy the TItles, AUthors and SOurce with optional parts of abstracts into papers under edition. This arrangement serves the special demands of a research laboratory by handling MEDLINE and CINAHL source data resulting after a search is performed with keywords specified for ongoing projects. Since the Ohio State University has a centrally founded mainframe system, the data upload, storage and mainframe operations are free.
Increasingly, owners of clinical information systems are turning to clinical data warehouses (CDWs) to store and to analyze their data. The CDW allows institutions to make better use of their clinical data that has been collected through its information systems. A CDW extracts data from these systems, transforms it into a usable form, and then allows users to view and analyze years of data across a large cross section of patient charts. Although warehouses have existed in healthcare for some time, there are relatively few institutions that maintain patient charts in a CDW. This is, in part, because of the challenges often seen when attempting to warehouse this type of data. These include integrating a diverse set of care practices and a variety of definitions for common data elements like medications, observations, treatments, units of measure, and even unique patient identifiers. In addition, these systems often struggle with a high level of inconsistent and/or incomplete data that must be cleaned up on a regular basis. Unlike other data warehouse systems, CDWs are often expected to gather data around the clock and in a manner that has minimum impact to the performance of the source Clinical Information Systems. Finally, CDWs often have a diverse range of clinical and administrative users. This often leads to a need for a variety of applications and/or tools for viewing and analyzing the data.
Reducing the patient dose while keeping the image noise at the same level is desired for x-ray CT examinations. In order to achieve the goal, we propose a new weighting scheme taking the validity of the data and redundant data samples into account. The method is evaluated with a new generalized version of the Feldkamp helical reconstruction algorithm. It allows us to enlarge the projection angular range used in reconstruction, and thus, to reduce the image noise by increasing the detector utilization rate to 100% without sacrificing the image quality or z-resolution. This concept can be adapted to other exact or approximate algorithms as far as they use redundant data samples.
ChromoWheel is an Internet browser application for generating whole-genome illustrations. It can be used to depict chromosomes, genes and relations between chromosomal loci. The circular layout of chromosomes is advantageous for showing relationships between different chromosomes, as the connecting line never crosses over a chromosome. All graphical image components are in the vector-based format Scalable Vector Graphics, which are highly scaleable and admit user interaction. ChromoWheel can either be run with user-provided data in the generic SFS format, or as a browser front-end for precompiled genomic data.
GOLDsurfer is a java-based analysis and graphics program for three-dimensional plotting of linkage disequilibrium (LD). Simultaneous presentation of LD measures, including recombination rate estimates and disease association statistics, helps to clarify LD patterns and facilitates interpretations based on multiple indices of local genetic data.
MOTIVATION: Generation of alternative transcripts from the same gene is an important biological event due to their contribution in creating functional diversity in eukaryotes. In this work, we choose the task of extracting information around this complex topic using a two-step procedure involving machine learning and information extraction. RESULTS: In the first step, we trained a classifier that inductively learns to identify sentences about physiological transcript diversity from the MEDLINE abstracts. Using a large hand-built corpus, we compared the sentence classification performance of various text categorization methods. Support vector machines (SVMs) followed by the maximum entropy classifier outperformed other methods for the sentence classification task. The SVM with the radial basis function kernel and optimized parameters achieved Fbeta-measure of 91% during the 4-fold cross validation and of 74% when applied to all sentences in more than 12 million abstracts of MEDLINE. In the second step, we identified eight frequently present semantic categories in the sentences and performed a limited amount of semantic role labeling. The role labeling step also achieved very high Fbeta-measure for all eight categories. AVAILABILITY: The results of our two-step procedure are summarized in the LSAT database of alternative transcripts. LSAT is available at http://www.bork.embl.de/LSAT CONTACT: shah@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Clustering of gene expression data is a standard technique used to identify closely related genes. In this paper, we develop a new clustering algorithm, MSC (Multi-Source Clustering), to perform exploratory analysis using two or more diverse sources of data. In particular, we investigate the problem of improving the clustering by integrating information obtained from gene expression data with knowledge extracted from biomedical text literature. In each iteration of algorithm MSC, an EM-type procedure is employed to bootstrap the model obtained from one data source by starting with the cluster assignments obtained in the previous iteration using the other data sources. Upon convergence, the two individual models are used to construct the final cluster assignment. We compare the results of algorithm MSC for two data sources with the results obtained when the clustering is applied on the two sources of data separately. We also compare it with that obtained using the feature level integration method that performs the clustering after simply concatenating the features obtained from the two data sources. We show that the z-scores of the clustering results from MSC are better than that from the other methods. To evaluate our clusters better, function enrichment results are presented using terms from the Gene Ontology database. Finally, by investigating the success of motif detection programs that use the clusters, we show that our approach integrating gene expression data and text data reveals clusters that are biologically more meaningful than those identified using gene expression data alone.
Recent papers and patents in iterative unsupervised learning have emphasized a new trend in clustering. It basically consists of penalizing solutions via weights on the instance points, somehow making clustering move toward the hardest points to cluster. The motivations come principally from an analogy with powerful supervised classification methods known as boosting algorithms. However, interest in this analogy has so far been mainly borne out from experimental studies only. This paper is, to the best of our knowledge, the first attempt at its formalization. More precisely, we handle clustering as a constrained minimization of a Bregman divergence. Weight modifications rely on the local variations of the expected complete log-likelihoods. Theoretical results show benefits resembling those of boosting algorithms and bring modified (weighted) versions of clustering algorithms such as k-means, fuzzy c-means, Expectation Maximization (EM), and k-harmonic means. Experiments are provided for all these algorithms, with a readily available code. They display the advantages that subtle data reweighting may bring to clustering.
The recently developed weighted backprojection filtration (WBPF) algorithm using data redundancy has capabilities that make this algorithm an attractive candidate for reconstructing images from motion-contaminated projection data. First, the WBPF algorithm is capable of reconstructing region-of-interest (ROI) images from reduced-scan fan-beam data, which have less data than the short-scan data required to reconstruct the entire field of view (FOV). Second, this algorithm can reconstruct ROI images from truncated data. Using phantom simulation studies, we demonstrate how these unique capabilities can be exploited to reduce the amount of motion-contaminated data used for reconstruction. In particular, we use examples from cardiac imaging to illustrate how off-center phantom positioning combined with phase-interval ROI reconstruction can result in the suppression of motion artifacts. In terms of temporal resolution, reduced-scan reconstruction with 45% of a full-scan dataset can be used to improve the temporal resolution of a short-scan reconstruction by 25.8% if ungated data are used. For data gated at 66 beats per minute, reduced-scan reconstruction with 45% of a full-scan dataset can be used to improve the temporal resolution of a short-scan reconstruction by 7.9%. As a result of our studies, we believe that the WBPF algorithm demonstrates the potential for reconstructing quality ROI images from motion-contaminated fan-beam data.
BACKGROUND: A cluster analysis is the most commonly performed procedure (often regarded as a first step) on a set of gene expression profiles. In most cases, a post hoc analysis is done to see if the genes in the same clusters can be functionally correlated. While past successes of such analyses have often been reported in a number of microarray studies (most of which used the standard hierarchical clustering, UPGMA, with one minus the Pearson's correlation coefficient as a measure of dissimilarity), often times such groupings could be misleading. More importantly, a systematic evaluation of the entire set of clusters produced by such unsupervised procedures is necessary since they also contain genes that are seemingly unrelated or may have more than one common function. Here we quantify the performance of a given unsupervised clustering algorithm applied to a given microarray study in terms of its ability to produce biologically meaningful clusters using a reference set of functional classes. Such a reference set may come from prior biological knowledge specific to a microarray study or may be formed using the growing databases of gene ontologies (GO) for the annotated genes of the relevant species. RESULTS: In this paper, we introduce two performance measures for evaluating the results of a clustering algorithm in its ability to produce biologically meaningful clusters. The first measure is a biological homogeneity index (BHI). As the name suggests, it is a measure of how biologically homogeneous the clusters are. This can be used to quantify the performance of a given clustering algorithm such as UPGMA in grouping genes for a particular data set and also for comparing the performance of a number of competing clustering algorithms applied to the same data set. The second performance measure is called a biological stability index (BSI). For a given clustering algorithm and an expression data set, it measures the consistency of the clustering algorithm's ability to produce biologically meaningful clusters when applied repeatedly to similar data sets. A good clustering algorithm should have high BHI and moderate to high BSI. We evaluated the performance of ten well known clustering algorithms on two gene expression data sets and identified the optimal algorithm in each case. The first data set deals with SAGE profiles of differentially expressed tags between normal and ductal carcinoma in situ samples of breast cancer patients. The second data set contains the expression profiles over time of positively expressed genes (ORF's) during sporulation of budding yeast. Two separate choices of the functional classes were used for this data set and the results were compared for consistency. CONCLUSION: Functional information of annotated genes available from various GO databases mined using ontology tools can be used to systematically judge the results of an unsupervised clustering algorithm as applied to a gene expression data set in clustering genes. This information could be used to select the right algorithm from a class of clustering algorithms for the given data set.
BACKGROUND: Microarray has been widely used to measure the relative amounts of every mRNA transcript from the genome in a single scan. Biologists have been accustomed to reading their experimental data directly from tables. However, microarray data are quite large and are stored in a series of files in a machine-readable format, so direct reading of the full data set is not feasible. The challenge is to design a user interface that allows biologists to usefully view large tables of raw microarray-based gene expression data. This paper presents one such interface--an electronic table (E-table) that uses fisheye distortion technology. RESULTS: The Fisheye Viewer for microarray-based gene expression data has been successfully developed to view MIAME data stored in the MAGE-ML format. The viewer can be downloaded from the project web site http://polaris.imt.uwm.edu:7777/fisheye/. The fisheye viewer was implemented in Java so that it could run on multiple platforms. We implemented the E-table by adapting JTable, a default table implementation in the Java Swing user interface library. Fisheye views use variable magnification to balance magnification for easy viewing and compression for maximizing the amount of data on the screen. CONCLUSION: This Fisheye Viewer is a lightweight but useful tool for biologists to quickly overview the raw microarray-based gene expression data in an E-table.