http://precedings.nature.com/subjects/bioinformatics/ Recently posted documents in Bioinformatics Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://dx.doi.org/10.1038/npre.2009.4000.1 The goal of the INCF Digital Atlasing Program is to provide the vision and direction necessary to make the rapidly growing collection of multidimensional data of the rodent brain (images, gene expression, etc.) widely accessible and usable to the international research community. This Digital Brain Atlasing Standards Task Force was formed in May 2008 to investigate the state of rodent brain digital atlasing, and formulate standards, guidelines, and policy recommendations.Our first objective has been the preparation of a detailed document that includes the vision and specific description of an infrastructure, systems and methods capable of serving the scientific goals of the community, as well as practical issues for achievingthe goals. This report builds on the 1st INCF Workshop on Mouse and Rat Brain Digital Atlasing Systems (Boline et al., 2007, Nature Preceedings, doi:10.1038/npre.2007.1046.1) and includes a more detailed analysis of both the current state and desired state of digital atlasing along with specific recommendations for achieving these goals. http://dx.doi.org/10.1038/npre.2009.4000.1 Tue, 24 Nov 2009 09:43:24 UTC The INCF Digital Atlasing Program: Report on Digital Atlasing Standards in the Rodent Brain doi:10.1038/npre.2009.4000.1 2009-11-24 Nature Precedings 2009-11-24T09:43:24Z Manuscript Neuroscience Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.4001.1 The syntax of LBFO represents the initial step toward the creation of a rigorously characterized, recursively defined, artificial language for the sole purpose of ontology development. The underlying idea is that maximally fruitful application of ontology requires accurate representation of reality in accordance with current textbook science. Hence, creating a robust, accurate representation of reality is a fundamental concern. An ontology represents general types of entities and relations between them. A domain ontology represents the general types and relations for a given domain of research. A top-level ontology represents the general types of entities in any domain of research. Ontologies serve many purposes in computerized collection, management, and storage of data. These applications include enhancement of storage and retrieval in a data system, integration of diverse systems, integration of semantic content on the web, and annotation of publications in a library setting.Successful application of ontologies has led to the creation of languages with the special purpose of implementing ontologies. A formalized ontology is an ontology expressed in accordance with the grammatical formation rules of an artificial language. Some existing ontology languages have been developed in order to serve specific functions that require expressibility limitations and expression of information in a manner that contributes to human misunderstanding and error. The most potentially detrimental effect is risked when an ontology is constructed in a language designed exclusively for computerized implementation. The result is a skewed representation of salient features of reality. An ontology development language has two purposes: one is to represent reality as accurately and completely as possible, the other is to achieve this in a manner that facilitates computerized implementation: these goals conflict. Validation requires expert human consensus, hence, an ontology should be developed in a language that is understandable to domain experts. However, such a language must be computer tractable, i.e., there must be a correspondence between the information expressed with a sentence and its grammatical structure such that information can be processed on the basis of syntax alone. LBFO will facilitate providing definitions and characterizations of features of reality in a way conformant with Basic Formal Ontology (BFO) thus ensuring maximal rigor and clarity. Since LBFO is a multi-sorted language, LBFO has resources to represent the ontological categories found in BFO and the universals defined in their terms in an economical and at the same time user-friendly way. BFO is a realist ontology in that it recognizes universals as an part of the world. BFO also recognizes the existence of both processes and continuants. A continuant is an individual that exists in full at each point in time in which it exists, a process is an individual that exists in stages and happens through time. Unlike a continuant, a process cannot be identified with any single stage at which it exists at a specific point in time. Capitalized variables range over universals, while lower-case variables range over individuals. Universal constants are upper-case. Individual constants are lower-case. The syntax of LBFO also distinguishes in a straightforward manner between variables for continuants, processes, and times. The syntax of LBFO contains precisely expressed grammatical-formation rules, so that its variables cannot be combined in a manner that results in category errors. The predicates of LBFO are such that the ontological category from which terms representing entities can be taken as arguments is specified in advance. Sentences which express category errors are not grammatically correct in LBFO.Since the demand for implementation often outstrips the demand for accurate representation, stand-alone ontologies are often left by the wayside. LBFO can serve as a bridge between domain experts, knowledge engineers, and implementation languages. The semantic apparatus of an FOL system serves as the basis for the models developed for implementation languages such as OWL and RDF. FOL is also a segregated dialect of Common Logic so there is a link to that international standard; hence, there is potential to develop middle-ware that maps LBFO to the variety of implementation languages that exist both now and in the future. Though there is much work to be done in perfecting LBFO, this first step in the process provides hope for achieving the goal of facilitating maximally accurate, rigorous representations of general features of reality. http://dx.doi.org/10.1038/npre.2009.4001.1 Mon, 23 Nov 2009 15:36:02 UTC LBFO: toward an artificial language for ontology development doi:10.1038/npre.2009.4001.1 2009-11-23 Leonard F. Jacuzzo Nature Precedings 2009-11-23T15:36:02Z Poster Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3971/version/1 An ontological representation of the entities relevant to biological research is urgently needed. The cell ontology developed by Bard and colleagues (CL) (Bard et al. 2005) makes a significant contribution towards fulfilling this need by providing an ontology of cell types. The CL has already proven useful for data annotation (e.g. Grumbling et al. 2006), although the ontology’s potential utility goes well beyond that specific application. For example, using the number of distinct cell types in an organism as a measure of biological complexity, Vogel and Chothia (2006) compared the proteomes of 38 organisms of varying complexity and identified patterns in the evolution and expansion of protein domain superfamilies. This work has implications for some of the fundamental questions in biology, such as understanding the processes by which physiology becomes more intricate, new cell types arise, and biological complexity increases. While Vogel and Chothia did not yet utilize the CL for this work, they cite Bard et al. (2005) and describe the ontology’s value for improving and extending their analysis. Thus, in addition to its great utility for database annotation, the CL has the potential to play a significant role in basic scientific inquiry.The prospect of using the CL (and other ontologies) for this type of scientific research is extremely exciting but also imposes requirements on the level of formal rigor applied in ontology development, on the adequacy of the ontology as a representation of reality, and on its adherence to community standards of best practice. It is with these things in mind that I examined the CL to determine whether any revision would be required before my research group could use it for scientific research.After carefully evaluating the CL, my overall impression is that it does not possess the rigor and exactness required of a reference ontology. Furthermore, the problems I see are significant enough that it would be difficult for my research group to use the CL as our application ontology. While some of the problems could be resolved by changing a relation or rewriting a definition, others would require careful rethinking of the ontology’s foundation, because they involve the scope and organizing principle of the ontology as a whole. http://precedings.nature.com/documents/3971/version/1 Thu, 12 Nov 2009 17:05:38 UTC Evaluation of the Cell Ontology (CL) hdl:10101/npre.2009.3971.1 2009-11-12 Lindsay G. Cowell Nature Precedings 2009-11-12T17:05:38Z Manuscript Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3960.1 Definitive diagnosis of malaria requires the demonstration through laboratory tests of the presence within the patient of malaria parasites or their components. Since malaria parasites can be present even in the absence of malaria, and since symptoms of malaria can be manifested even in the absence of malaria parasites, malaria diagnosis raises important issues for the adequate understanding of disease, etiology and diagnosis. One approach to the resolution of these issues adopts a realist view, according to which the needed clarifications will be derived from a careful representation of the entities on the side of the patient which form the ultimate truthmakers for clinical statements. We address a challenge to this realist approach relating to the diagnosis of malaria, and show how this challenge can be resolved by appeal to Basic Formal Ontology (BFO) and to the Ontology for General Medical Science (OGMS) constructed in its terms. http://dx.doi.org/10.1038/npre.2009.3960.1 Mon, 09 Nov 2009 10:30:10 UTC Malaria Diagnosis and the Plasmodium Life Cycle: the BFO Perspective doi:10.1038/npre.2009.3960.1 2009-11-09 Werner Ceusters Nature Precedings 2009-11-09T10:30:10Z Manuscript Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3938/version/1 Two of the most significant formats for biomedical ontologies are the Open Biomedical Ontologies Format (OBOF) and the Web Ontology Language (OWL). To make it possible to translate ontologies between these two representation formats, the National Center for Biomedical Ontology (NCBO) has developed a mapping between the OBOF and OWL formats as well as inter-conversion software. The goal was to allow the sharing of tools, ontologies, and associated data between the OBOF and Semantic Web communities.OBOF does not have a formal grammar, so the NCBO had to capture its intended semantics to map it to OWL.This official NCBO mapping was used to make all OBO Foundry ontologies available in OWL. Availability: This mapping functionality can be embedded into OBO-Edit and Protégé-OWL ontology editors. This software is available at: http://bioontology.org/wiki/index.php/OboInOwl:Main_Page http://precedings.nature.com/documents/3938/version/1 Wed, 04 Nov 2009 16:35:19 UTC The NCBO OBOF to OWL Mapping hdl:10101/npre.2009.3938.1 2009-11-04 Dilvan A. Moreira Nature Precedings 2009-11-04T16:35:19Z Manuscript Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3932/version/1 Metabolic networks are among the most widely studied biological systems. The topology and interconnections of metabolic reactions have been well described for many species, but are not sufficient to understand how their activity is regulated in living organisms. The principles directing the dynamic organisation of reaction fluxes remain poorly understood. Cyclic structures are thought to play a central role in the homeostasis of biological systems and in their resilience to a changing environment. In this work, we investigate the role of fluxes of matter cycling in metabolic networks. First, we introduce a methodology for the computation of cyclic and acyclic fluxes in metabolic networks, adapted from an algorithm initially developed to study cyclic fluxes in trophic networks. Subsequently, we apply this methodology to the analysis of three metabolic systems, including the central metabolism of wild type and a deletion mutant of Escherichia coli, erythrocyte metabolism and the central metabolism of the bacterium Methylobacterium extorquens. The role of cycles in driving and maintaining the performance of metabolic functions upon perturbations is unveiled through these examples. This methodology may be used to further investigate the role of cycles in living organisms, their pro-activity and organisational invariance, leading to a better understanding of biological entailment and information processing. http://precedings.nature.com/documents/3932/version/1 Mon, 02 Nov 2009 17:25:38 UTC Organising metabolic networks: cycles in flux distributions hdl:10101/npre.2009.3932.1 2009-11-02 Jean-Marc Schwartz Nature Precedings 2009-11-02T17:25:38Z Manuscript Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3920/version/1 Tracking Parkinson’s disease (PD) symptom progression often uses the Unified Parkinson’s Disease Rating Scale (UPDRS), which requires the patient’s presence in clinic, and time-consuming physical examinations by trained medical staff. Thus, symptom monitoring is costly and logistically inconvenient for patient and clinical staff alike, also hindering recruitment for future large-scale clinical trials. Here, for the first time, we demonstrate rapid, remote replication of UPDRS assessment with clinically useful accuracy (about 7.5 UPDRS points difference from the clinicians’ estimates), using only simple, self-administered, and non-invasive speech tests. We characterize speech with signal processing algorithms, extracting clinically useful features of average PD progression. Subsequently, we select the most parsimonious model with a robust feature selection algorithm, and statistically map the selected subset of features to UPDRS using linear and nonlinear regression techniques, which include classical least squares and non-parametric classification and regression trees (CART). We verify our findings on the largest database of PD speech in existence (~6,000 recordings from 42 PD patients, recruited to a six-month, multi-centre trial). These findings support the feasibility of frequent, remote and accurate UPDRS tracking. This technology could play a key part in telemonitoring frameworks that enable large-scale clinical trials into novel PD treatments. http://precedings.nature.com/documents/3920/version/1 Thu, 29 Oct 2009 15:21:58 UTC Accurate telemonitoring of Parkinson’s disease progression by non-invasive speech tests hdl:10101/npre.2009.3920.1 2009-10-29 Nature Precedings 2009-10-29T15:21:58Z Manuscript Neuroscience Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3917/version/1 Recently Granich et al. at the World Health Organization (WHO) concluded, using mathematical modeling, that HIV epidemics could be eliminated within a decade. They assumed all individuals would be tested annually and every infected individual (regardless of stage of infection) would be put on treatment. Based on this modeling study the WHO is considering using universal testing and treatment as an HIV elimination strategy. Here we examine the study by Granich et al. and assess its validity. We present new analyses of their model by varying assumptions and parameter values. We find that under certain very optimistic assumptions HIV elimination would be (theoretically) possible, but it would take at least 70 years. To obtain this result we assumed ~65% of symptomatic and ~20% of asymptomatic individuals would be treated per year; ARVs would reduce infectivity of treated individuals a hundred fold, and only 5% of symptomatic individuals would give up treatment per year. Even under optimistic assumptions we find elimination to be unlikely. For example, we show if ~65% of symptomatic individuals are treated per year and treated individuals are completely noninfectious, HIV will remain endemic with a prevalence of 34% and an incidence of 2% per year. We conclude that the model developed by Granich et al., when used with realistic parameter values, does not show HIV elimination is possible. However our modeling results show treatment could act as an effective prevention tool and significantly reduce transmission, even if only symptomatic individuals receive ARVs. Treatment should first, and foremost, be used for therapeutic purposes. Hence, we recommend – when resources are limited – targeting those in need of treatment. Such a strategy would be ethical, feasible and epidemiologically sound. We advise that models used as health policy tools should be carefully evaluated and their results interpreted with caution. http://precedings.nature.com/documents/3917/version/1 Thu, 29 Oct 2009 14:56:08 UTC Voluntary universal testing and treatment is unlikely to lead to HIV elimination: a modeling analysis hdl:10101/npre.2009.3917.1 2009-10-29 Nature Precedings 2009-10-29T14:56:08Z Manuscript Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3913.1 A new approach to design a dynamic model of genes with multiple autonomous regulatory modules by evolution in silico is proposed. The approach is based on Genetic Algorithms, with new crossover operators especially designed for these purposes. The approach exploits the subbasin-portal architecture of the fitness functions suitable for this kind of evolutionary modeling. The effectiveness of the approach is demonstrated on a series of benchmark tests. http://dx.doi.org/10.1038/npre.2009.3913.1 Thu, 29 Oct 2009 10:09:24 UTC Design of a dynamic model of genes with multiple autonomous regulatory modules by evolution in silico doi:10.1038/npre.2009.3913.1 2009-10-29 Nature Precedings 2009-10-29T10:09:24Z Manuscript Biotechnology Developmental Biology Genetics & Genomics Bioinformatics Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3898/version/1 A bacterial strain, designated Aeromonas sp. kumar, was isolated from a water sample collected from Red tide Bloom occurred in the region of Gulf of Mannar region, Puthumadam Coast, India and the strain was identified using 16S rRNA based identification. During the sample collection, microbiology analysis was done to study the morphology of the bacteria. Pure culture of strain was maintained through out the study. DNA was isolated and sequenced using 16S rRNA primers. A length of 1452 nucleotide was sequenced and was put in public data base for obtaining accession number. The sequence was studied using MEGA 4, to estimate the evolutionary distances and to construct the Phylogenetic tree. Along with that Regulatory elements and Transcription factors were studied using BPROM tool. In genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream (towards the 5’ region of the sense strand). The objective of the study is to predict the regulatory elements which are -10 box, -35box and three Transcription Factors (rpoD19, rpoD17 and araC) with their binding sites in the 16S rRNA gene of Aeromonas sp. kumar. The gene bank accession number for 16S rRNA gene of Aeromonas sp. kumar is FJ896014. http://precedings.nature.com/documents/3898/version/1 Wed, 28 Oct 2009 14:41:34 UTC 16S rRNA based identification of Aeromonas sp. kumar by constructing phylogenetic tree and identification of regulatory elements from the harmful Red Tide bloom, Gulf of Mannar hdl:10101/npre.2009.3898.1 2009-10-28 P. Kumar Nature Precedings 2009-10-28T14:41:34Z Manuscript Ecology Microbiology Bioinformatics http://creativecommons.org/licenses/by/3.0/