Bielefeld, Universiẗat, Diss. 2002.

Cette thèse porte sur le développement d'approches bioinformatiques exploitant de l'information de contextes génomiques et métaboliques afin de générer des annotations fonctionnelles de gènes prokaryotes, et comporte deux projets principaux. Le premier projet focalise sur les activités enzymatiques orphelines de séquence. Environ 27% des activités définies par le International Union of Biochemistry and Molecular Biology sont encore aujourd'hui orphelines. Pour celles-ci, les méthodes bioinformatiques traditionnelles ne peuvent proposer de gènes candidats; il est donc impératif d'utiliser des méthodes exploitant des informations contextuelles dans ces cas. La stratégie CanOE (fishingCandidate genes for Orphan Enzymes) a été développée et rajoutée à la plateforme MicroScope dans ce but, intégrant des informations génomiques et métaboliques sur des milliers d'organismes prokaryotes afin de localiser des gènes probants pour des activités orphelines. Le projet miroir au précédent est celui des protéines de fonction inconnue. Un projet collaboratif a été initié au Genoscope afin de formaliser les stratégies d'exploration des fonctions de familles protéiques prokaryotes. Une version pilote du projet a été mise en place sur la famille “DUF849” dont une fonction enzymatique avait été récemment découverte. Des stratégies de proposition d'activités enzymatiques alternatives et d'établissement de sous familles isofonctionnelles ont été mises en place dans le cadre de cette thèse, afin de guider les expérimentations de paillasse et d'analyser leurs résultats. / The subject of this thesis concerns the development of bioinformatic strategies exploiting genomic and metabolic contextual information in order to generate functional annotations for prokaryote genes. Two main projects were involved during this work: the first focuses on sequence-orphan enzymatic activities. Today, roughly 27% of activities defined by International Union of Biochemistry and Molecular Biology are sequence-orphans. For these, traditional bioinformatic approaches cannot propose candidate genes. It is thus imperative to use alternative, context-based approaches in such cases. The CanOE strategy fishing Candidate genes for Orphan Enzymes) was developed and added to the MicroScope bioinformatics platform in this aim. It integrates genomic and metabolic information across thousands of prokaryote genomes in order to locate promising gene candidates for orphan activities. The mirror project focuses on protein families of unknown function. A collaborative project has been set up at the Genoscope in hope of formalising functional exploration strategies for prokaryote protein families. A pilot version was created on the “DUF849” Pfam family, for which a single activity had recently been elucidated. Strategies for proposing novel functions and activities and creating isofunctional sub-families were researched, so as to guide biochemical experimentations and to analyse their results.

We present an annotation management system for cloud-based platforms, which is called “CloudNotes�. CloudNotes enables the annotation management feature in the scalable Hadoop and MapRedue platforms. In CloudNotes system, every piece of data may have one or more annotations associate with it, and these annotations will be propagated when the data is being transformed through the MapReduce jobs. Such an annotation management system is important for understanding the provenance and quality of data, especially in applications that deal with integration of scientific and biological data at unprecedented scale and complexity. We propose several extensions to the Hadoop platform that allow end-users to add and retrieve annotations seamlessly. Annotations in CloudNotes will be generated, propagated and managed in a distributed manner. We address several challenges that include attaching annotations to data at various granularities in Hadoop, annotating data in flat files with no known schema until query time, and creating and storing the annotations is a distributed fashion. We also present new storage mechanisms and novel indexing techniques that enable adding the annotations in small increments although Hadoop’s file system is optimized for large batch processing.

This research deals with annotations in scholarly work. Annotations have been studied by many people. A significant amount of research has shown that instead of implementing domain specific annotation applications a better approach is to develop general purpose annotation toolkits that can be used to create domain specific applications. A video annotation toolkit along with toolkits for searching, retrieving, analyzing and presenting videos can help achieve the broader goal of creating integrated work spaces for scholarly work in humanities research similar to existing environments in such fields as mathematics, engineering, statistics, software development and bioinformatics. This research implements a video annotation toolkit and evaluates it by looking at its usefulness in creating applications for different areas. It was found that many areas of study in the arts and sciences can benefit from a video annotation application tailored to their specific needs and that an annotation toolkit can significantly reduce the time for developing such applications. The toolkit was engineered through successive refinements of prototype applications developed for different application areas. The toolkit design was also guided by a set of features identified by the research community for an ideal general purpose annotation toolkit. This research contributes by combining these two different approaches to toolkit design and construction into a hybrid approach. This approach could be useful for similar or related efforts.

This research deals with annotations in scholarly work. Annotations have been studied by many people. A significant amount of research has shown that instead of implementing domain specific annotation applications a better approach is to develop general purpose annotation toolkits that can be used to create domain specific applications. A video annotation toolkit along with toolkits for searching, retrieving, analyzing and presenting videos can help achieve the broader goal of creating integrated work spaces for scholarly work in humanities research similar to existing environments in such fields as mathematics, engineering, statistics, software development and bioinformatics. This research implements a video annotation toolkit and evaluates it by looking at its usefulness in creating applications for different areas. It was found that many areas of study in the arts and sciences can benefit from a video annotation application tailored to their specific needs and that an annotation toolkit can significantly reduce the time for developing such applications. The toolkit was engineered through successive refinements of prototype applications developed for different application areas. The toolkit design was also guided by a set of features identified by the research community for an ideal general purpose annotation toolkit. This research contributes by combining these two different approaches to toolkit design and construction into a hybrid approach. This approach could be useful for similar or related efforts.

No description available.

La composition monomérique de polymères joue un rôle essentiel dans la comparaison de structures et dans la biologie de synthèse. Cependant, la plupart des ressources moléculaires en ligne donne accès à la structure atomique des molécules et non à leur structure monomérique. Nous avons donc créé un logiciel appelé smiles2monomers (s2m) pour inférer la structure monomérique passer des atomes aux monomères. L’algorithme sous-jacent se déroule en deux phases : une phase de recherche par isomorphisme de sous graphe des monomères au sein de la structure atomique puis une recherche du meilleur pavage non chevauchant des monomères trouvés. La recherche est basée sur un index markovien améliorant les vitesses de recherche de 30% par rapport à l’état de l’art. Le pavage est lui constitué d’un algorithme glouton couplé à un raffinement par “branch & cut”. s2m a été testé sur deux jeux de données déjà annotés. Il retrouve les annotations manuelles avec une excellente sensibilité en des temps très courts. Notre équipe développe Norine, base de données de référence de polymères particuliers appelés Peptides Non Ribosomiques (NRP). s2m, exécuté sur l’ensemble des données de Norine, a mis à jour de nombreuses annotations erronées en base. s2m est donc à la fois capable de créer de nouvelles annotations et d’en corriger des anciennes. Les nouvelles annotations nous servent à la fois à découvrir de nouveaux NRP, de nouvelles fonctionnalités NRP et potentiellement dans le futur à synthétiser des NRP non naturels. / The monomeric composition of polymers is powerful for structure comparison and synthetic biology, among others. However, most of the online molecular resources only provide atomic structures but not monomeric structures. So, we designed a software called smiles2monomers (s2m) to infer monomeric structures from chemical ones. The underlying algorithm is composed of two steps: a search of the monomers using a subgraph isomorphism algorithm fitted to our data and a tiling algorithm to obtain the best coverage of the polymer by non-overlapping monomers. The search is based on a Markovian index improving the execution time by 30% compared to the state of art. The tiling is performed using a greedy algorithm refined by a “branch & cut” algorithm. s2m had been tested on two different already annotated datasets. The software reconstructed the manual annotations with an excellent sensibility in a very short time. Norine database, the reference knowledge base about specific polymers called Non Ri bosomal Peptides (NRP), is developed by our research group. s2m, executed on the Norine database, alerted us about wrong manual annotations. So, s2m not only creates new annotations, but also facilitates the process of annotation curation. The new annotations generated by the software are currently used for the discovery of new NRP, new activities and may be used to create completely new and artificial NRP.

Techn. Universiẗat, Diss., 2004--Berlin.

Stuttgart, Univ., Studienarb., 2003.

Techn. Universiẗat, Diss., 2005--München.