Dovetailing biology and chemistry: integrating the Gene Ontology with the ChEBI chemical ontology.

BACKGROUND: The Gene Ontology (GO) facilitates the description of the action of gene products in a biological context. Many GO terms refer to chemical entities that participate in biological processes. To facilitate accurate and consistent systems-wide biological representation, it is necessary to integrate the chemical view of these entities with the biological view of GO functions and processes. We describe a collaborative effort between the GO and the Chemical Entities of Biological Interest (ChEBI) ontology developers to ensure that the representation of chemicals in the GO is both internally consistent and in alignment with the chemical expertise captured in ChEBI. RESULTS: We have examined and integrated the ChEBI structural hierarchy into the GO resource through computationally-assisted manual curation of both GO and ChEBI. Our work has resulted in the creation of computable definitions of GO terms that contain fully defined semantic relationships to corresponding chemical terms in ChEBI. CONCLUSIONS: The set of logical definitions using both the GO and ChEBI has already been used to automate aspects of GO development and has the potential to allow the integration of data across the domains of biology and chemistry. These logical definitions are available as an extended version of the ontology from http://purl.obolibrary.org/obo/go/extensions/go-plus.owl.

A database for chemical proteomics: ChEBI.

Chemical proteomics is concerned with the identification of protein targets interacting with small molecules. Hence, the availability of a high quality and free resource storing small molecules is essential for the future development of the field. The Chemical Entities of Biological Interest (ChEBI) database is one such database. The scope of ChEBI includes any constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer, etc., identifiable as a separately distinguishable entity. These entities in question are either products of nature or synthetic products used to intervene in the processes of living organisms. In addition, ChEBI contains a chemical ontology which relates the small molecules with each other thereby making it easier for users to discover data. The ontology also describes the biological roles that the small molecules are active in. The ChEBI database also provides a central reference point in which to access a variety of bioinformatics data points such as pathways and their biochemical reactions; expression data; protein sequence and structures.

The chemical information ontology: provenance and disambiguation for chemical data on the biological semantic web.

Cheminformatics is the application of informatics techniques to solve chemical problems in silico. There are many areas in biology where cheminformatics plays an important role in computational research, including metabolism, proteomics, and systems biology. One critical aspect in the application of cheminformatics in these fields is the accurate exchange of data, which is increasingly accomplished through the use of ontologies. Ontologies are formal representations of objects and their properties using a logic-based ontology language. Many such ontologies are currently being developed to represent objects across all the domains of science. Ontologies enable the definition, classification, and support for querying objects in a particular domain, enabling intelligent computer applications to be built which support the work of scientists both within the domain of interest and across interrelated neighbouring domains. Modern chemical research relies on computational techniques to filter and organise data to maximise research productivity. The objects which are manipulated in these algorithms and procedures, as well as the algorithms and procedures themselves, enjoy a kind of virtual life within computers. We will call these information entities. Here, we describe our work in developing an ontology of chemical information entities, with a primary focus on data-driven research and the integration of calculated properties (descriptors) of chemical entities within a semantic web context. Our ontology distinguishes algorithmic, or procedural information from declarative, or factual information, and renders of particular importance the annotation of provenance to calculated data. The Chemical Information Ontology is being developed as an open collaborative project. More details, together with a downloadable OWL file, are available at http://code.google.com/p/semanticchemistry/ (license: CC-BY-SA).

PIDO: the primary immunodeficiency disease ontology.

MOTIVATION: Primary immunodeficiency diseases (PIDs) are Mendelian conditions of high phenotypic complexity and low incidence. They usually manifest in toddlers and infants, although they can also occur much later in life. Information about PIDs is often widely scattered throughout the clinical as well as the research literature and hard to find for both generalists as well as experienced clinicians. Semantic Web technologies coupled to clinical information systems can go some way toward addressing this problem. Ontologies are a central component of such a system, containing and centralizing knowledge about primary immunodeficiencies in both a human- and computer-comprehensible form. The development of an ontology of PIDs is therefore a central step toward developing informatics tools, which can support the clinician in the diagnosis and treatment of these diseases. RESULTS: We present PIDO, the primary immunodeficiency disease ontology. PIDO characterizes PIDs in terms of the phenotypes commonly observed by clinicians during a diagnosis process. Phenotype terms in PIDO are formally defined using complex definitions based on qualities, functions, processes and structures. We provide mappings to biomedical reference ontologies to ensure interoperability with ontologies in other domains. Based on PIDO, we developed the PIDFinder, an ontology-driven software prototype that can facilitate clinical decision support. PIDO connects immunological knowledge across resources within a common framework and thereby enables translational research and the development of medical applications for the domain of immunology and primary immunodeficiency diseases.

ChemicalTagger: A tool for semantic text-mining in chemistry.

BACKGROUND: The primary method for scientific communication is in the form of published scientific articles and theses which use natural language combined with domain-specific terminology. As such, they contain free owing unstructured text. Given the usefulness of data extraction from unstructured literature, we aim to show how this can be achieved for the discipline of chemistry. The highly formulaic style of writing most chemists adopt make their contributions well suited to high-throughput Natural Language Processing (NLP) approaches. RESULTS: We have developed the ChemicalTagger parser as a medium-depth, phrase-based semantic NLP tool for the language of chemical experiments. Tagging is based on a modular architecture and uses a combination of OSCAR, domain-specific regex and English taggers to identify parts-of-speech. The ANTLR grammar is used to structure this into tree-based phrases. Using a metric that allows for overlapping annotations, we achieved machine-annotator agreements of 88.9% for phrase recognition and 91.9% for phrase-type identification (Action names). CONCLUSIONS: It is possible parse to chemical experimental text using rule-based techniques in conjunction with a formal grammar parser. ChemicalTagger has been deployed for over 10,000 patents and has identified solvents from their linguistic context with >99.5% precision.

A versatile platform for comprehensive chip-based explorative cytometry.

Analysis of the immense complexity of the immune system is increasingly hampered by technical limitations of current methodologies, especially for multiparameter- and functional analysis of samples containing small numbers of cells. We here present a method, which is based on the stepwise functional manipulation and analysis of living immune cells that are self-immobilized within microfluidic chips using automated epifluorescence microscopy overcoming current limitations for comprehensive immunophenotyping. Crossvalidation with flow cytometry revealed a 10-fold increased sensitivity and a comparable specificity. By using small sample volumes and cell numbers (2-10 microl, down to 20,000 cells), we were able to analyze a virtually unlimited number of intracellular and surface markers even on living immune cells. We exemplify the scientific and diagnostic potential of this method by (1) identification and phenotyping of rare cells, (2) comprehensive analysis of very limited sample volume, and (3) deep immunophenotyping of human B-cells after in vitro differentiation. Finally, we propose an informatic model for annotation and comparison of cytometric data by using an ontology-based approach. The chip-based cytometry introduced here turned out to be a very useful tool to enable a stepwise exploration of precious, small cell-containing samples with an virtually unlimited number of surface- and intracellular markers.

Chemical Markup, XML and the World-Wide Web. 8. Polymer Markup Language.

Polymers are among the most important classes of materials but are only inadequately supported by modern informatics. The paper discusses the reasons why polymer informatics is considerably more challenging than small molecule informatics and develops a vision for the computer-aided design of polymers, based on modern semantic web technologies. The paper then discusses the development of Polymer Markup Language (PML). PML is an extensible language, designed to support the (structural) representation of polymers and polymer-related information. PML closely interoperates with Chemical Markup Language (CML) and overcomes a number of the previously identified challenges.

Poly(2-oxazolines) in biological and biomedical application contexts.

Polyoxazolines of various architectures and chemical functionalities can be prepared in a living and therefore controlled manner via cationic ring-opening polymerisation. They have found widespread applications, ranging from coatings to pigment dispersants. Furthermore, several polyoxazolines are water-soluble or amphiphilic and relatively non-toxic, which makes them interesting as biomaterials. This paper reviews the development of polyoxazoline-based polymers in biological and biomedical application contexts since the beginning of the millennium. This includes nanoscalar systems such as membranes and nanoparticles, drug and gene delivery applications, as well as stimuli-responsive systems.

Statistical approach to understand MALDI-TOFMS matrices: discovery and evaluation of new MALDI matrices.

A statistical approach is described to better understand the role of the matrix during a MALDI-TOFMS experiment. Potential matrix molecules were selected based on a rational experimental design and subsequently screened in order to investigate whether a certain compound can act as a matrix for synthetic polymers. The tested compounds were selected from a pool of 11 000 molecules based on descriptor calculations and a subsequent D-optimal design selection procedure. This approach selected 59 organic compounds that were then investigated for their ability to act a matrix for synthetic polymers in MALDI-TOFMS experiments. Within this contribution, we focus on the discussion of new MALDI-TOFMS matrixes that were discovered in the course of the screening. At least 10 new matrices were identified, and 5 of these were subsequently tested more closely with a variety of different synthetic polymers of different molecular weights revealing good to excellent performance of these new matrices.

High-throughput screening and optimization of photoembossed relief structures.

A methodology for the rapid design, screening, and optimization of coating systems with surface relief structures, using a combination of statistical experimental design, high-throughput experimentation, data mining, and graphical and mathematical optimization routines was developed. The methodology was applied to photopolymers used in photoembossing applications. A library of 72 films was prepared by dispensing a given amount of sample onto a chemically patterned substrate consisting of hydrophilic areas separated by fluorinated hydrophobic barriers. Film composition and film processing conditions were determined using statistical experimental design. The surface topology of the films was characterized by automated AFM. Subsequently, models explaining the dependence of surface topologies on sample composition and processing parameters were developed and used for screening a virtual 4000-membered in silico library of photopolymer lacquers. Simple graphical optimization or Pareto algorithms were subsequently used to find an ensemble of formulations, which were optimal with respect to a predefined set of properties, such as aspect ratio and shape of the relief structures.

New titanium imido synthons: syntheses and supramolecular structures.

Reactions of Ti(NMe(2))(2)Cl(2) with a wide range of primary alkyl and arylamines RNH(2) afforded the corresponding 5-coordinate imido titanium compounds Ti(NR)Cl(2)(NHMe(2))(2) (R = (t)Bu (1), (i)Pr (2), CH(2)Ph (3), Ph (4), 2,6-C(6)H(3)Me(2) (5), 2,6-C(6)H(3)(i)Pr(2) (6), 2,4,6-C(6)H(2)F(3) (7), 2,3,5,6-C(6)HF(4) (8), C(6)F(5) (9), 4-C(6)H(4)Cl (10), 2,3,5,6-C(6)HCl(4) (11), 2-C(6)H(4)CF(3) (12), 2-C(6)H(4)(t)Bu (13)). The compounds 1-13 are monomeric in solution but in the solid state form either N-H...Cl hydrogen bonded dimers or chains or perfluorophenyl pi-stacked chains, depending on the imido R-group. The compound 13 was also prepared in a "one-pot" synthesis from RNH(2) and Ti(NMe(2))(4) and Me(3)SiCl. Reaction of certain Ti(NR)Cl(2)(NHMe(2))(2) compounds with an excess of pyridine afforded the corresponding bis- or tris-pyridine analogues [Ti(NR)Cl(2)(py)(x)](y) (x = 3, y = 1; x = y = 2), and the structure of Ti(2)(NC(6)F(5))(2)Cl(2)(mu-Cl)(2)(py)(4) shows pi-stacking of perfluorophenyl rings. Reaction of Ti(NMe(2))(2)Cl(2) with cross-linked aminomethyl polystyrene gave quantitative conversion to the corresponding solid-supported titanium imido complex. This paper represents the first detailed study of how supramolecular structures of imido compounds may be influenced by simple variation of the imido ligand N-substituent.

Discovery and evaluation of highly active imidotitanium ethylene polymerisation catalysts using high throughput catalyst screening.

A family of ca. 50 imidotitanium precatalysts [Ti(NR)(Me(3)[9]aneN(3))Cl(2)](R = alkyl or aryl; Me(3)[9]aneN(3)= 1,4,7-trimethyltriazacyclononane) were prepared in good yields using semi-automated procedures; high-throughput screening techniques identified seven highly active ethylene polymerisation precatalysts with activities in the range ca. 3 400 to 10 000 kg(PE) mol(-1) h(-1) bar(-1).