Graph Databases in Molecular Biology

The article presents an approach to modeling domain ontologies based on graph databases. Ontology is traditionally considered as a means of studying and formalizing the subject area. Based on ontologies, knowledge bases of information systems are formed, which can later be replenished and used to study certain applied aspects of the subject area. At the same time, with the development of NoSQL technologies and graph databases aimed at optimizing work with related data, it becomes possible to design a data warehouse without a strict pre-established domain model. Due to the obvious graph nature of ontologies, graph databases are a promising solution for storing and working with ontologies. However, with all the similarities, the ontology and data models used in graph DBMSs are not so easy to combine. The paper proposes an approach to the integration of ontological and graph models of knowledge representation and considers its application in creating a database for a prototype of a web ontology editor. Visual tools for editing ontologies are described, an algorithm for layer-by-layer rendering of a directed graph is given, a mechanism for generating dynamic forms for editing classes and ontology instances is described, and basic support for ontological design patterns is implemented.

This paper presents an approach to detect behavioral design patterns from source code using static analysis techniques. It depends on the concept of Code Property Graph and enriching graph with relationships and properties specific to Design Patterns, to simplify the process of Design Pattern detection. This approach used NoSQL graph database (Neo4j) and uses graph traversal language (Gremlin) for doing graph matching. Our approach, converts the tasks of design pattern detection to a graph matching task by representing Design Patterns in form of graph queries and running it on graph database.

Graph databases such as neo4j are designed to handle and integrate big data from heterogeneous sources. For flexibility and performance they do not ensure data quality through schemata but leave it to the application level. In this paper, we present a model-driven approach for data integration through graph databases with data sources in relational databases. We model query and update operations in neo4j by triple graph grammars and map these to Gremlin code for execution. In this way we provide a model-based approach to data integration that is both visual and formal while providing the data quality assurances of a schema-based solution.

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George Kenyon called on 11 December 2006 to inform me of his resignation from the presidency of the IUBMB: this was a consequence of an apparent conflict of interest with his new activity at the National Science Foundation. I expressed to him my deepest regret, and a sincere one, due to his talent, capable of making him become an important president of the IUBMB. I would like to express to George my personal gratitude and that of the Executive Committee of the IUBMB for his generous nature and the collegial environment he had immediately created. It was obviously unlucky for me to leave the ‘comfortable’ position of president elect and take up the IUBMB presidency two and half years before my term of office would have begun. Bill Whelan, in his email of congratulations wrote, ‘Another Harland Wood’. In fact, Harland Wood succeeded Feodor Lynen in 1979; a few weeks after their election to president-elect and president, respectively, Feodor Lynen had died. Already in previous reflections I had asked myself if the IUBMB, just 50 years old, still fulfills the important role it had in the past. The congresses, the conferences, the special meetings, the IUBMB jubilee lectures, the Wood-Whelan fellowship program remain as milestones in the activity of the Union. The IUBMB journals represent a great achievement in the field of science publishing and of biochemistry education. The last 50 years have created a revolution in the field of biochemistry and molecular biology. At the same time a revolution has been created by the Internet in the way of communication among scientist and in the way papers are published. Did IUBMB evolve at the same pace? Are we missing something? Should we give an opportunity to our Adhering Bodies to judge the Union and to give, if needed, new impulses? A comparison with the other Unions would be also useful, to see how they have evolved and are evolving. An analysis should be made to assess this and other aspects of a complex organization like the Union in a changing world. It is, I believe, accepted by almost everyone, that biochemistry and molecular biology are the basis of modern biological sciences: without biochemistry and molecular biology we cannot understand the basis of diseases and in particular those that most affect human beings, such as cancer, and cardiovascular and degenerative diseases. Also in the field of plants, biochemistry and molecular biology have occupied important positions, both in the systematic as well as in the understanding of plant physiology and of the active principle present in plants. Also environmental studies require our disciplines to answer questions such as the effect of the surroundings on our bodies, on the survival of species and on the maintenance of biodiversity. Natural medicine and phytochemicals require molecular explanations and mechanisms that can largely be given only by biochemistry and molecular biology. The role of biochemistry and molecular biology is becoming every day more evident as a consequence of the refinement of the methods that it can offer, useful to dissect molecular pathways, to find targets of drugs and to propose potential remedies. A form of applied biochemistry is biotechnology, with its exponentially growing result output, ready to be used as a medication, a prophylactic measure or a nutritional recommendation. In fact nutrition is a field per se, where the introduction of biochemistry and molecular biology has given a great impetus. Is such a central image of biochemistry and molecular biology generally perceived? Certainly, not enough. One of the roles of the Union should be to cast a new and more correct light on the merits of its disciplines, with due respect for all the fields that have stemmed from it. Can we augment the visibility of these values, not only vis-a-vis the new, more target-oriented disciplines but also in public opinion? Can we make the name of IUBMB well known and appreciated not only within specialized circles? Revamping the image of the IUBMB and of its structures, in the direction of a needed basic foundation to understand disease, both in terms of education and research, may become attractive for donors and make more support available for further reaching the Union’s goals. Received 4 January 2007; accepted 7 January 2007 Address correspondence to: Angelo Azzi, Vascular Biology Laboratory, Office 622, JM USDA-HNRCA at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Tel: þ1 617 556 3271. Fax: þ1 617 556 3224. E-mail: angelo.azzi@tufts.edu IUBMBLife, 59(4 – 5): 196 – 198, April –May 2007

It has been noted that the integration of modern data of paleontology, comparative morphology, developmental biology, and molecular genetics forms the basis for understanding the mechanisms of evolutionary transformations of ontogeny. Paleontological and morphological evidence of the evolutionary changes in ontogeny are considered based on the data of cell and molecular biology and developmental genetics. It is shown that reorganizations of gene regulatory cascades (primarily Hox genes) play a key role in the evolution of the axial organization of animals and modifications of the limb structure of metazoans, whereas the emergence and development of new types of structures was apparently determined by the emergence of new populations of stem cells in embryogenesis (for example, neural crest cells in the evolution of vertebrates).

Whole mount in situ hybridization (WISH) is a common technique in molecular biology laboratories used to study gene expression through the localization of specific mRNA transcripts within whole mount specimen. This technique (adapted from Albertson and Yelick, 2005) was used in an upper level undergraduate Comparative Vertebrate Biology laboratory classroom at Syracuse University. The first two thirds of the Comparative Vertebrate Biology lab course gave students the opportunity to study the embryology and gross anatomy of several organisms representing various chordate taxa primarily via traditional dissections and the use of models. The final portion of the course involved an innovative approach to teaching anatomy through observation of vertebrate development employing molecular techniques in which WISH was performed on zebrafish embryos. A heterozygous fibroblast growth factor 8 a (fgf8a) mutant line, ace, was used. Due to Mendelian inheritance, ace intercrosses produced wild type, heterozygous, and homozygous ace/fgf8a mutants in a 1:2:1 ratio. RNA probes with known expression patterns in the midline and in developing anatomical structures such as the heart, somites, tailbud, myotome, and brain were used. WISH was performed using zebrafish at the 13 somite and prim-6 stages, with students performing the staining reaction in class. The study of zebrafish embryos at different stages of development gave students the ability to observe how these anatomical structures changed over ontogeny. In addition, some ace/fgf8a mutants displayed improper heart looping, and defects in somite and brain development. The students in this lab observed the normal development of various organ systems using both external anatomy as well as gene expression patterns. They also identified and described embryos displaying improper anatomical development and gene expression (i.e., putative mutants). For instructors at institutions that do not already own the necessary equipment or where funds for lab and curricular innovation are limited, the financial cost of the reagents and apparatus may be a factor to consider, as will the time and effort required on the part of the instructor regardless of the setting. Nevertheless, we contend that the use of WISH in this type of classroom laboratory setting can provide an important link between developmental genetics and anatomy. As technology advances and the ability to study organismal development at the molecular level becomes easier, cheaper, and increasingly popular, many evolutionary biologists, ecologists, and physiologists are turning to research strategies in the field of molecular biology. Using WISH in a Comparative Vertebrate Biology laboratory classroom is one example of how molecules and anatomy can converge within a single course. This gives upper level college students the opportunity to practice modern biological research techniques, leading to a more diversified education and the promotion of future interdisciplinary scientific research.

Several application domains hold highly connected data, like supply chain and social network. In this context, NoSQL graph databases raise as a promising solution since relationships are first class citizens in their data model. Nevertheless, a traditional database design methodology initially defines a conceptual schema of the domain data, and the Enhanced Entity-Relationship (EER) model is a common tool. This paper presents a rule-based conversion process from an EER schema to Neo4j schema constraints, as Neo4j is the most representative NoSQL graph database management system with an expressive data model. Different from related work, our conversion process deals with all EER model concepts and generates rules for ensuring schema constraints through a set of Cypher instructions ready to run into a Neo4j database instance, as Neo4J is a schemaless system, and it is not possible to create a schema a priori. We also present an experimental evaluation that demonstrates the viability of our process in terms of performance.

Location-based social network users typically publish information about their location and activity (in the form of keywords) along time, thus providing the mobility data management research community with complex and voluminous data. In this work, we handle this kind of data as sequences in the Spatio-Temporal-Keyword (STK) domain. This modeling is coherent with the concept of semantic trajectories that has recently attracted the interest of this community. Our paper focuses on the efficient processing of pattern queries over the STK domain, hence called Spatio-Temporal-Keyword Pattern (STKP) queries. Our approach is based on efficient index structures that take into account the triple nature of these patterns and is developed in a NoSQL graph database. Through an extensive experimental study over real-life datasets, we demonstrate the effectiveness and efficiency of our proposal.

This paper proposes a concept of an accessible BIM database that supports integration with geometry enabling simplified and efficient queries of the IFC-based building model. The simplified schema, BIMRL, is shown to be significantly effective for the purpose of an implementation of an automated BIM-based rule checking system. The schema has been shown to successfully work in both traditional RDBMS and the NoSQL graph database. It complements a missing piece in the current research of automated rule checking, which mostly focuses on the formulation and representation of computable rules involving logic, checking algorithm, and parameterization. Even though these present approaches have largely assumed that data is available and easily accessible from a building model, this assumption is typically infeasible in a real-world implementation. Building rules require not only base data explicitly available in the model but also higher level semantic concepts that typically involve multiple relationships and spatial operations, which cannot be captured explicitly in the model. Without addressing this issue, a rule checking system will severely underperform and will be filled with opaque algorithms that act as black-boxes.

BackgroundThe generation and analysis of high-throughput sequencing data are becoming a major component of many studies in molecular biology and medical research. Illumina's Genome Analyzer (GA) and HiSeq instruments are currently the most widely used sequencing devices. Here, we comprehensively evaluate properties of genomic HiSeq and GAIIx data derived from two plant genomes and one virus, with read lengths of 95 to 150 bases.ResultsWe provide quantifications and evidence for GC bias, error rates, error sequence context, effects of quality filtering, and the reliability of quality values. By combining different filtering criteria we reduced error rates 7-fold at the expense of discarding 12.5% of alignable bases. While overall error rates are low in HiSeq data we observed regions of accumulated wrong base calls. Only 3% of all error positions accounted for 24.7% of all substitution errors. Analyzing the forward and reverse strands separately revealed error rates of up to 18.7%. Insertions and deletions occurred at very low rates on average but increased to up to 2% in homopolymers. A positive correlation between read coverage and GC content was found depending on the GC content range.ConclusionsThe errors and biases we report have implications for the use and the interpretation of Illumina sequencing data. GAIIx and HiSeq data sets show slightly different error profiles. Quality filtering is essential to minimize downstream analysis artifacts. Supporting previous recommendations, the strand-specificity provides a criterion to distinguish sequencing errors from low abundance polymorphisms.

Recent developments in high-throughput sequencing (HTS) technologies have enabled the reconstruction of complete genome sequence and nucleosome and methylation maps from ancient individuals. A diversity of degradation reactions affect DNA molecules after an organism dies, introducing specific nucleotide misincorporation patterns in HTS data that are typically exploited to distinguish modern contaminants and authentic DNA templates. In this study, we used two different DNA polymerases to amplify Illumina TruSeq DNA libraries built on DNA extracts from ancient equines. The AmpliTaq Gold, widely used in ancient DNA studies, generated amplified libraries showing typical misincorporation patterns. Such patterns were partially lost following AccuPrime Pfx amplification, for which a two-fold reduction of endogenous content was also observed. This is explained by the inability of the AccuPrime Pfx to bypass uracils, which represent the most common post-mortem base modification and derive from the post-mortem deamination of cytosines. Our study, therefore, reveals that amplification of TruSeq DNA libraries with AccuPrime Pfx increases the cost of whole-genome sequencing for samples showing substantial levels of DNA degradation and creates atypical nucleotide misincorporation patterns for data authentication. The method can, however, be exploited to identify ancient methylation marks, and potentially, nucleosome occupancy maps.Statement of significance After an organism dies, DNA molecules are subjected to degradation resulting in fragmentation and bases modifications. After high- throughput sequencing (HTS), it is possible to detect the molecular signature of these damages, demonstrating that the data generated is authentic. DNA extracts from fossil remains indeed contain, besides endogenous ancient molecules, a variety of modern contaminants, but only the former generally exhibits molecular signatures typical of post-mortem damage. Our study reveals that these signatures depend on the protocol used for amplifying DNA samples. It thus helps defining better guidelines for authenticating ancient HTS data. Our results also reveal one molecular approach that limits our ability to exploit the whole complexity of ancient DNA molecules preserved in fossil specimens but can help track ancient methylation marks.Data availability The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are contained within the paper.

There is real need among researchers for data in molecular biology, due to the explosive development in this field. Information extraction techniques have been developed in this specific domain, to extract structured information from the literature. The National Library of Medicine provides access to 12 million MEDLINE citations, accessible via PubMed. Information retrieval techniques which are used to select documents that are relevant according to user request. As other domains in medicine, biomolecular scientific literature is indexed by MeSH terms. Automatic identification of protein and gene names in scientific articles is an important step in the indexing process, since proteins and genes are often associated with multiple names, and authors alternate between these synonyms. In this article we assess the contribution of specialized terminologies in the field of molecular biology compared to MeSH.

Contribution of the Pitié-Salpêtrière Hospital to French Anesthesiology

The past year has been an eventful one for the Journal of Lipid Research (JLR). The Directors of Lipid Research, Inc. (LRI), the owner of the Journal since its inception in 1959, are pleased to make some important announcements that should be of great interest to our authors and readers. The first of these is the transfer of ownership of the JLR to the American Society for Biochemistry and Molecular Biology (ASBMB) in July 2003. In June 2000, LRI entered into an agreement with the ASBMB to manage the publication of the Journal.