Machine learning tools for protein annotation: the cases of transmembrane β-barrel and myristoylated proteins

Biology is now a “Big Data Science” thanks to technological advancements allowing the characterization of the whole macromolecular content of a cell or a collection of cells. This opens interesting perspectives, but only a small portion of this data may be experimentally characterized. From this derives the demand of accurate and efficient computational tools for automatic annotation of biological molecules. This is even more true when dealing with membrane proteins, on which my research project is focused leading to the development of two machine learning-based methods: BetAware-Deep and SVMyr. BetAware-Deep is a tool for the detection and topology prediction of transmembrane beta-barrel proteins found in Gram-negative bacteria. These proteins are involved in many biological processes and primary candidates as drug targets. BetAware-Deep exploits the combination of a deep learning framework (bidirectional long short-term memory) and a probabilistic graphical model (grammatical-restrained hidden conditional random field). Moreover, it introduced a modified formulation of the hydrophobic moment, designed to include the evolutionary information. BetAware-Deep outperformed all the available methods in topology prediction and reported high scores in the detection task. Glycine myristoylation in Eukaryotes is the binding of a myristic acid on an N-terminal glycine. SVMyr is a fast method based on support vector machines designed to predict this modification in dataset of proteomic scale. It uses as input octapeptides and exploits computational scores derived from experimental examples and mean physicochemical features. SVMyr outperformed all the available methods for co-translational myristoylation prediction. In addition, it allows (as a unique feature) the prediction of post-translational myristoylation. Both the tools here described are designed having in mind best practices for the development of machine learning-based tools outlined by the bioinformatics community. Moreover, they are made available via user-friendly web servers. All this make them valuable tools for filling the gap between sequential and annotated data.

Un commento a Lucrezio, De rerum natura 6.703-1089

La tesi consiste in un commento scientifico ai versi 703-1089 del VI libro di Lucrezio, dove sono discussi vari mirabilia della natura (le piene estive del Nilo, i luoghi Averni, l’escursione termica dei pozzi, alcune fonti prodigiose e il magnete). Nell’introduzione, si traccia una rapida panoramica del VI libro per contestualizzare al suo interno il passo oggetto del commento; ci si concentra, poi, sul significato della meraviglia e del meraviglioso nell’opera, anche a confronto con la tradizione paradossografica. Seguono il testo, corredato di un sintetico apparato critico, e la traduzione. Nel commento, che intende valorizzare il côté letterario, filosofico e scientifico dell’opera, sono affrontati i più rilevanti problemi testuali ed esegetici, oltre a questioni di ordine grammaticale, linguistico, stilistico e metrico. Chiudono il lavoro due appendici di natura critico-testuale.

Le contexte linguistique et la tradition de langue hebraïque de la Secunda (deuxième colonne des Hexaples d'Origène)

Le terme Secunda désigne la deuxième colonne de la synopse hexaplaire d’Origène. Cette synopse comportait six colonnes, d’où le nom Hexapla utilisé pour la désigner : la première contenait le texte hébreu original de l’Ancien Testament, la deuxième (Secunda) sa transcription phonétique en caractères grecs, les quatre autres les différentes traductions grecques de la Bible. La présence de graphèmes de vocaliques grecs dans la Secunda permet de mener une étude grammaticale complète de cette source, d’un point de vue phonétique et morphologique. Il manque encore actuellement une recherche qui développe le rapport entre la tradition hébraïque de la Secunda, telle qu’elle ressort de la transcription, et les autres traditions hébraïques attestées : celles sans graphèmes vocaliques (c’est-à-dire la tradition samaritaine et le corpus qumranien) et les traditions plus tardives et vocalisées pendant la période médiévale (les traditions massorétique tibérienne, babylonienne et palestinienne). Ce dernier point est précisément l’objet de cette thèse, qui vise à mieux comprendre le statut de l’hébreu de la Secunda, ses relations avec les autres traditions hébraïques et sa place dans l’histoire de la langue. Cette question est abordée à travers différentes étapes : en partant d’une étude phonétique et morphologique de la langue hébraïque de la colonne, on arrive à une hypothèse de datation qui permet une comparaison directe entre l’hébreu hexaplaire et les autres traditions mentionnées ci-dessus. La comparaison entre la Secunda et les autres traditions est cruciale pour situer correctement la Secunda dans l’histoire de la langue hébraïque : au niveau synchronique, elle permet de mettre en évidence ses éléments dialectaux, documentés dans les transcriptions de la Secunda et dans les traditions de la même époque ; au niveau diachronique, elle fournit des terminus ante ou post quem pour des phénomènes bien attestés dans les traditions tardives.

A maximum entropy approach to disturbed ecosystems

The current climate crisis requires a comprehensive understanding of biodiversity to acknowledge how ecosystems’ responses to anthropogenic disturbances may result in feedback that can either mitigate or exacerbate global warming. Although ecosystems are dynamic and macroecological patterns change drastically in response to disturbance, dynamic macroecology has received insufficient attention and theoretical formalisation. In this context, the maximum entropy principle (MaxEnt) could provide an effective inference procedure to study ecosystems. Since the improper usage of entropy outside its scope often leads to misconceptions, the opening chapter will clarify its meaning by following its evolution from classical thermodynamics to information theory. The second chapter introduces the study of ecosystems from a physicist’s viewpoint. In particular, the MaxEnt Theory of Ecology (METE) will be the cornerstone of the discussion. METE predicts the shapes of macroecological metrics in relatively static ecosystems using constraints imposed by static state variables. However, in disturbed ecosystems with macroscale state variables that change rapidly over time, its predictions tend to fail. In the final chapter, DynaMETE is therefore presented as an extension of METE from static to dynamic. By predicting how macroecological patterns are likely to change in response to perturbations, DynaMETE can contribute to a better understanding of disturbed ecosystems’ fate and the improvement of conservation and management of carbon sinks, like forests. Targeted strategies in ecosystem management are now indispensable to enhance the interdependence of human well-being and the health of ecosystems, thus avoiding climate change tipping points.