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The Comprehensive Microbial Resource.

One challenge presented by large-scale genome sequencing efforts is effective display of uniform information to the scientific community. The Comprehensive Microbial Resource (CMR) contains robust annotation of all complete microbial genomes and allows for a wide variety of data retrievals. The bacterial information has been placed on the Web at http://www.tigr.org/CMR for retrieval using standard web browsing technology. Retrievals can be based on protein properties such as molecular weight or hydrophobicity, GC-content, functional role assignments and taxonomy. The CMR also has special web-based tools to allow data mining using pre-run homology searches, whole genome dot-plots, batch downloading and traversal across genomes using a variety of datatypes.

Bacteria↗

LGICdb: the ligand-gated ion channel database.

Ligand-Gated Ion Channels (LGIC) are polymeric transmembrane proteins involved in the fast response to numerous neurotransmitters. All these receptors are formed by homologous subunits and the last two decades revealed an unexpected wealth of genes coding for these subunits. The Ligand-Gated Ion Channel database (LGICdb) has been developed to handle this increasing amount of data. The database aims to provide only one entry for each gene, containing annotated nucleic acid and protein sequences. The repository is carefully structured and the entries can be retrieved by various criteria. In addition to the sequences, the LGICdb provides multiple sequence alignments, phylogenetic analyses and atomic coordinates when available. The database is accessible via the World Wide Web (http://www.pasteur.fr/recherche/banques/LGIC /LGIC.html), where it is continuously updated. The version 16 (September 2000) available for download contained 333 entries covering 34 species.

Databases, Factual↗

HugeIndex: a database with visualization tools for high-density oligonucleotide array data from normal human tissues.

High-density oligonucleotide arrays are a powerful tool for uncovering changes in global gene expression in various disease states. To this end, it is essential to first characterize the variations of gene expression in normal physiological processes. We established the Human Gene Expression (HuGE) Index database (www.HugeIndex.org) to serve as a public repository for gene expression data on normal human tissues using high-density oligonucleotide arrays. This resource currently contains the results of 59 gene expression experiments on 19 human tissues. We provide interactive tools for researchers to query and visualize our data over the Internet. To facilitate data analysis, we cross-reference each gene on the array with its annotation in the LocusLink database at NCBI.

Computer Graphics↗

The GENETPIG database: a tool for comparative mapping in pig (Sus scrofa).

The GENETPIG database has been established for storing and disseminating the results of the European project: 'GENETPIG: identification of genes controlling economic traits in pig'. The partners of this project have mapped about 630 porcine and human ESTs onto the pig genome. The database collects the mapping results and links them to other sources of mapping data; this includes pig maps as well as available comparative mapping information. Functional annotation of the mapped ESTs is also given when a significant similarity to cognate genes was established. The database is accessible for consultation via the Internet at http://www.infobiogen.fr/services/Genetpig/.

Animals↗

Pathbase: a database of mutant mouse pathology.

Pathbase is a database that stores images of the abnormal histology associated with spontaneous and induced mutations of both embryonic and adult mice including those produced by transgenesis, targeted mutagenesis and chemical mutagenesis. Images of normal mouse histology and strain-dependent background lesions are also available. The database and the images are publicly accessible (http://www.pathbase.net) and linked by anatomical site, gene and other identifiers to relevant databases; there are also facilities for public comment and record annotation. The database is structured around a novel ontology of mouse disorders (MPATH) and provides high-resolution downloadable images of normal and diseased tissues that are searchable through orthogonal ontologies for pathology, developmental stage, anatomy and gene attributes (GO terms), together with controlled vocabularies for type of genetic manipulation or mutation, genotype and free text annotation for mouse strain and additional attributes. The database is actively curated and data records assessed by pathologists in the Pathbase Consortium before publication. The database interface is designed to have optimal browser and platform compatibility and to interact directly with other web-based mouse genetic resources.

Animals↗

Integr8 and Genome Reviews: integrated views of complete genomes and proteomes.

Integr8 is a new web portal for exploring the biology of organisms with completely deciphered genomes. For over 190 species, Integr8 provides access to general information, recent publications, and a detailed statistical overview of the genome and proteome of the organism. The preparation of this analysis is supported through Genome Reviews, a new database of bacterial and archaeal DNA sequences in which annotation has been upgraded (compared to the original submission) through the integration of data from many sources, including the EMBL Nucleotide Sequence Database, the UniProt Knowledgebase, InterPro, CluSTr, GOA and HOGENOM. Integr8 also allows the users to customize their own interactive analysis, and to download both customized and prepared datasets for their own use. Integr8 is available at http://www.ebi.ac.uk/integr8.

DNA, Archaeal↗

DoOP: Databases of Orthologous Promoters, collections of clusters of orthologous upstream sequences from chordates and plants.

DoOP (http://doop.abc.hu/) is a database of eukaryotic promoter sequences (upstream regions) aiming to facilitate the recognition of regulatory sites conserved between species. The annotated first exons of human and Arabidopsis thaliana genes were used as queries in BLAST searches to collect the most closely related orthologous first exon sequences from Chordata and Viridiplantae species. Up to 3000 bp DNA segments upstream from these first exons constitute the clusters in the chordate and plant sections of the Database of Orthologous Promoters. Release 1.0 of DoOP contains 21,061 chordate clusters from 284 different species and 7548 plant clusters from 269 different species. The database can be used to find and retrieve promoter sequences of a given gene from various species and it is also suitable to see the most trivial conserved sequence blocks in the orthologous upstream regions. Users can search DoOP with either sequence or text (annotation) to find promoter clusters of various genes. In addition to the sequence data, the positions of the conserved sequence blocks derived from multiple alignments, the positions of repetitive elements and the positions of transcription start sites known from the Eukaryotic Promoter Database (EPD) can be viewed graphically.

Animals↗

BIOVERSE: enhancements to the framework for structural, functional and contextual modeling of proteins and proteomes.

We have made a number of enhancements to the previously described Bioverse web server and computational biology framework (http://bioverse.compbio.washington.edu). In this update, we provide an overview of the new features available that include: (i) expansion of the number of organisms represented in the Bioverse and addition of new data sources and novel prediction techniques not available elsewhere, including network-based annotation; (ii) reengineering the database backend and supporting code resulting in significant speed, search and ease-of use improvements; and (iii) creation of a stateful and dynamic web application frontend to improve interface speed and usability. Integrated Java-based applications also allow dynamic visualization of real and predicted protein interaction networks.

Computer Graphics↗

Mapping of transcription start sites in Saccharomyces cerevisiae using 5' SAGE.

A minimally addressed area in Saccharomyces cerevisiae research is the mapping of transcription start sites (TSS). Mapping of TSS in S.cerevisiae has the potential to contribute to our understanding of gene regulation, transcription, mRNA stability and aspects of RNA biology. Here, we use 5' SAGE to map 5' TSS in S.cerevisiae. Tags identifying the first 15-17 bases of the transcripts are created, ligated to form ditags, amplified, concatemerized and ligated into a vector to create a library. Each clone sequenced from this library identifies 10-20 TSS. We have identified 13,746 unique, unambiguous sequence tags from 2231 S.cerevisiae genes. TSS identified in this study are consistent with published results, with primer extension results described here, and are consistent with expectations based on previous work on transcription initiation. We have aligned the sequence flanking 4637 TSS to identify the consensus sequence A(A(rich))5NPyA(A/T)NN(A(rich))6, which confirms and expands the previous reported PyA(A/T)Pu consensus pattern. The TSS data allowed the identification of a previously unrecognized gene, uncovered errors in previous annotation, and identified potential regulatory RNAs and upstream open reading frames in 5'-untranslated region.

Base Sequence↗

MGOS: A resource for studying Magnaporthe grisea and Oryza sativa interactions.

The MGOS (Magnaporthe grisea Oryza sativa) web-based database contains data from Oryza sativa and Magnaporthe grisea interaction experiments in which M. grisea is the fungal pathogen that causes the rice blast disease. In order to study the interactions, a consortium of fungal and rice geneticists was formed to construct a comprehensive set of experiments that would elucidate information about the gene expression of both rice and M. grisea during the infection cycle. These experiments included constructing and sequencing cDNA and robust long-serial analysis gene expression libraries from both host and pathogen during different stages of infection in both resistant and susceptible interactions, generating >50,000 M. grisea mutants and applying them to susceptible rice strains to test for pathogenicity, and constructing a dual O. sativa-M. grisea microarray. MGOS was developed as a central web-based repository for all the experimental data along with the rice and M. grisea genomic sequence. Community-based annotation is available for the M. grisea genes to aid in the study of the interactions.

Computational Biology↗

Crystallization and preliminary X-ray diffraction studies on the bicupin YwfC from Bacillus subtilis.

A central tenet of evolutionary biology is that proteins with diverse biochemical functions evolved from a single ancestral protein. A variation on this theme is that the functional repertoire of proteins in a living organism is enhanced by the evolution of single-chain multidomain polypeptides by gene-fusion or gene-duplication events. Proteins with a double-stranded beta-helix (cupin) scaffold perform a diverse range of functions. Bicupins are proteins with two cupin domains. There are four bicupins in Bacillus subtilis, encoded by the genes yvrK, yoaN, yxaG and ywfC. The extensive phylogenetic information on these four proteins makes them a good model system to study the evolution of function. The proteins YvrK and YoaN are oxalate decarboxylases, whereas YxaG is a quercetin dioxygenase. In an effort to aid the functional annotation of YwfC as well as to obtain a complete structure-function data set of bicupins, it was proposed to determine the crystal structure of YwfC. The bicupin YwfC was crystallized in two crystal forms. Preliminary crystallographic studies were performed on the diamond-shaped crystals, which belonged to the tetragonal space group P422. These crystals were grown using the microbatch method at 298 K. Native X-ray diffraction data from these crystals were collected to 2.2 A resolution on a home source. These crystals have unit-cell parameters a = b = 68.7, c = 211.5 A. Assuming the presence of two molecules per asymmetric unit, the V(M) value was 2.3 A3 Da(-1) and the solvent content was approximately 45%. Although the crystals appeared less frequently than the tetragonal form, YwfC also crystallizes in the monoclinic space group P2(1), with unit-cell parameters a = 46.7, b = 106.3, c = 48.7 A, beta = 92.7 degrees.

Amino Acid Sequence↗

Primary and community care workforce planning and development.

AIM: This article reports a study that provided primary and community care managers with information, allowing them to: (a) evaluate the size and mix of their workforce; and (b) develop knowledgeable and skilled teams to meet the demands of growing and changing services. BACKGROUND: Primary and community care services are growing in the United Kingdom, but workforce planning and development, despite their wide-ranging cost and quality implications, have not received the same attention. Indeed, most primary and community care workforce planning and development issues are universal. Demand 1-1 side workforce planning is concerned not only with the number, but also with staff mix; but how these autonomous and isolated practitioners spend their time is unique. The other side of the equation, workforce supply, raises many recruitment and retention challenges for managers in many countries. Any country's main workforce planning methods apply equally well to primary care, but each is flawed. A second, main problem is that the methods lead to fragmented services, whereas modern workforce planning methods should be multidisciplinary. Consequently, it has never been more important for managers to have data and algorithms to develop appropriate care teams. METHOD: A large and versatile workforce database, profiling 304 English primary care trusts using demographic, socio-economic, mortality, morbidity, staffing and performance workforce-related variables, compiled in 2002 and updated yearly, is described. Data were supplemented with a systematic literature review leading to a 340-item annotated bibliography; and qualitative interviews with managers. RESULTS: Workforce size and mix are historical and irrational at best. Moreover, the number of variables that influence staffing is growing, thereby complicating workforce planning. CONCLUSION: Evaluating and adjusting the size and mix of teams using empirically determined community demand and performance variables based on the area's socio-economic characteristics is feasible.

Community Health Nursing↗

Recognition of transmembrane segments in proteins: review and consistency-based benchmarking of internet servers.

Membrane proteins perform a number of crucial functions as transporters, receptors, and components of enzyme complexes. Identification of membrane proteins and prediction of their topology is thus an important part of genome annotation. We present here an overview of transmembrane segments in protein sequences, summarize data from large-scale genome studies, and report results of benchmarking of several popular internet servers.

Algorithms↗

A factor analysis model for functional genomics.

BACKGROUND: Expression array data are used to predict biological functions of uncharacterized genes by comparing their expression profiles to those of characterized genes. While biologically plausible, this is both statistically and computationally challenging. Typical approaches are computationally expensive and ignore correlations among expression profiles and functional categories. RESULTS: We propose a factor analysis model (FAM) for functional genomics and give a two-step algorithm, using genome-wide expression data for yeast and a subset of Gene-Ontology Biological Process functional annotations. We show that the predictive performance of our method is comparable to the current best approach while our total computation time was faster by a factor of 4000. We discuss the unique challenges in performance evaluation of algorithms used for genome-wide functions genomics. Finally, we discuss extensions to our method that can incorporate the inherent correlation structure of the functional categories to further improve predictive performance. CONCLUSION: Our factor analysis model is a computationally efficient technique for functional genomics and provides a clear and unified statistical framework with potential for incorporating important gene ontology information to improve predictions.

Algorithms↗

Automatic annotation of medical records.

One of the research projects running at the medical informatics department of the Institute of Computer Science AS CR explores the problem of medical information representation and development of electronic health record (EHR). With respect to this effort an interesting problem arises: how to transfer knowledge from a medical record written in a free text form into a structured electronic format represented by the EHR. Currently, this task was solved by writing extraction rules (regular expressions) for every element of information that is to be extracted from the medical record. However, such approach is very time consuming and requires supervision of a skilled programmer whenever the target area of medicine is changed. In this article we explore the possibility to mechanize this process by automatically generating the extraction rules from a pre-annotated corpus of medical records. Since we are currently in the phase of data acquisition and preliminary tests we will not present any final results, rather we will sketch the technologies we intend to use and describe the tools that were developed so far as a part of this project.

Electronic Health Records↗

Medicolegal ramifications of electronic fetal monitoring during labor.

Fetal heart rate patterns play a significant role in the modern day obstetric care. They also play a significant role in medicolegal allegations of negligence when the fetus suffers injury. Proper interpretation of the fetal monitor tracing is only one factor in the evaluation of the reasonableness of obstetric care. Appropriate care and optimal defense both derive from reasonable interpretation of pertinent clinical data, including the monitor strip, along with timely pursuit of a thoughtful, properly annotated, plan of care.

Birth Injuries↗

Computational prediction of miRNAs in Arabidopsis thaliana.

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression in animals and plants. Comparative genomic computational methods have been developed to predict new miRNAs in worms, flies, and humans. Here, we present a novel single genome approach for the detection of miRNAs in Arabidopsis thaliana. This was initiated by producing a candidate miRNA-target data set using an algorithm called findMiRNA, which predicts potential miRNAs within candidate precursor sequences that have corresponding target sites within transcripts. From this data set, we used a characteristic divergence pattern of miRNA precursor families to select 13 potential new miRNAs for experimental verification, and found that corresponding small RNAs could be detected for at least eight of the candidate miRNAs. Expression of some of these miRNAs appears to be under developmental control. Our results are consistent with the idea that targets of miRNAs encompass a wide range of transcripts, including those for F-box factors, ubiquitin conjugases, Leucine-rich repeat proteins, and metabolic enzymes, and that regulation by miRNAs might be widespread in the genome. The entire set of annotated transcripts in the Arabidopsis genome has been run through find MiRNA to yield a data set that will enable identification of potential miRNAs directed against any target gene.

Algorithms↗

Discovering regulatory binding-site modules using rule-based learning.

Transcription factors regulate expression by binding selectively to sequence sites in cis-regulatory regions of genes. It is therefore reasonable to assume that genes regulated by the same transcription factors should all contain the corresponding binding sites in their regulatory regions and exhibit similar expression profiles as measured by, for example, microarray technology. We have used this assumption to analyze genome-wide yeast binding-site and microarray expression data to reveal the combinatorial nature of gene regulation. We obtained IF-THEN rules linking binding-site combinations (binding-site modules) to genes with particular expression profiles, and thereby provided testable hypotheses on the combinatorial coregulation of gene expression. We showed that genes associated with such rules have a significantly higher probability of being bound by the same transcription factors, as indicated by a genome-wide location analysis, than genes associated with only common binding sites or similar expression. Furthermore, we also found that such genes were significantly more often biologically related in terms of Gene Ontology annotations than genes only associated with common binding sites or similar expression. We analyzed expression data collected under different sets of stress conditions and found many binding-site modules that are conserved over several of these condition sets, as well as modules that are specific to particular biological responses. Our results on the reoccurrence of binding sites in different modules provide specific data on how binding sites may be combined to allow a large number of expression outcomes using relatively few transcription factors.

Algorithms↗