A new paradigm for the folding of ribonucleic acids

De récentes découvertes montrent le rôle important que joue l’acide ribonucléique (ARN) au sein des cellules, que ce soit le contrôle de l’expression génétique, la régulation de plusieurs processus homéostasiques, en plus de la transcription et la traduction de l’acide désoxyribonucléique (ADN) en protéine. Si l’on veut comprendre comment la cellule fonctionne, nous devons d’abords comprendre ses composantes et comment ils interagissent, et en particulier chez l’ARN. La fonction d’une molécule est tributaire de sa structure tridimensionnelle (3D). Or, déterminer expérimentalement la structure 3D d’un ARN s’avère fort coûteux. Les méthodes courantes de prédiction par ordinateur de la structure d’un ARN ne tiennent compte que des appariements classiques ou canoniques, similaires à ceux de la fameuse structure en double-hélice de l’ADN. Ici, nous avons amélioré la prédiction de structures d’ARN en tenant compte de tous les types possibles d’appariements, dont ceux dits non-canoniques. Cela est rendu possible dans le contexte d’un nouveau paradigme pour le repliement des ARN, basé sur les motifs cycliques de nucléotides ; des blocs de bases pour la construction des ARN. De plus, nous avons dévelopées de nouvelles métriques pour quantifier la précision des méthodes de prédiction des structures 3D des ARN, vue l’introduction récente de plusieurs de ces méthodes. Enfin, nous avons évalué le pouvoir prédictif des nouvelles techniques de sondage de basse résolution des structures d’ARN.Recent findings show the important role of ribonucleic acid (RNA) within the cell, be it the control of gene expression, the regulation of several homeostatic processes, in addition to the transcription and translation of deoxyribonucleic acid (DNA) into protein. If we wish to understand how the cell works, we first need to understand its components and how they interact, and in particular for RNA. The function of a molecule is tributary of its three-dimensional (3D) structure. However, experimental determination of RNA 3D structures imparts great costs. Current methods for RNA structure prediction by computers only take into account the classical or canonical base pairs, similar to those found in the well-celebrated DNA double helix. Here, we improved RNA structure prediction by taking into account all possible types of base pairs, even those said non-canonicals. This is made possible in the context of a new paradigm for the folding of RNA, based on nucleotide cyclic motifs (NCM): basic blocks for the construction of RNA. Furthermore, we have developed new metrics to quantify the precision of RNA 3D structure prediction methods, given the recent introduction of many of those methods. Finally, we have evaluated the predictive power of the latest low-resolution RNA structure probing techniques

Les feuillets beta dans les protéines : annotation, comparaison et construction

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

On Docking, Scoring and Assessing Protein-DNA Complexes in a Rigid-Body Framework

We consider the identification of interacting protein-nucleic acid partners using the rigid body docking method FTdock, which is systematic and exhaustive in the exploration of docking conformations. The accuracy of rigid body docking methods is tested using known protein-DNA complexes for which the docked and undocked structures are both available. Additional tests with large decoy sets probe the efficacy of two published statistically derived scoring functions that contain a huge number of parameters. In contrast, we demonstrate that state-of-the-art machine learning techniques can enormously reduce the number of parameters required, thereby identifying the relevant docking features using a miniscule fraction of the number of parameters in the prior works. The present machine learning study considers a 300 dimensional vector (dependent on only 15 parameters), termed the Chemical Context Profile (CCP), where each dimension reflects a specific type of protein amino acid-nucleic acid base interaction. The CCP is designed to capture the chemical complementarities of the interface and is well suited for machine learning techniques. Our objective function is the Chemical Context Discrepancy (CCD), which is defined as the angle between the native system's CCP vector and the decoy's vector and which serves as a substitute for the more commonly used root mean squared deviation (RMSD). We demonstrate that the CCP provides a useful scoring function when certain dimensions are properly weighted. Finally, we explore how the amino acids on a protein's surface can help guide DNA binding, first through long-range interactions, followed by direct contacts, according to specific preferences for either the major or minor grooves of the DNA

RKB: a Semantic Web knowledge base for RNA

Increasingly sophisticated knowledge about RNA structure and function requires an inclusive knowledge representation that facilitates the integration of independently –generated information arising from such efforts as genome sequencing projects, microarray analyses, structure determination and RNA SELEX experiments. While RNAML, an XML-based representation, has been proposed as an exchange format for a select subset of information, it lacks domain-specific semantics that are essential for answering questions that require expert knowledge. Here, we describe an RNA knowledge base (RKB) for structure-based knowledge using RDF/OWL Semantic Web technologies. RKB extends a number of ontologies and contains basic terminology for nucleic acid composition along with context/model-specific structural features such as sugar conformations, base pairings and base stackings. RKB (available at http://semanticscience.org/projects/rkb) is populated with PDB entries and MC-Annotate structural annotation. We show queries to the RKB using description logic reasoning, thus opening the door to question answering over independently-published RNA knowledge using Semantic Web technologies

Fire Activity and Severity in the Western US Vary along Proxy Gradients Representing Fuel Amount and Fuel Moisture

Numerous theoretical and empirical studies have shown that wildfire activity (e.g., area burned) at regional to global scales may be limited at the extremes of environmental gradients such as productivity or moisture. Fire activity, however, represents only one component of the fire regime, and no studies to date have characterized fire severity along such gradients. Given the importance of fire severity in dictating ecological response to fire, this is a considerable knowledge gap. For the western US, we quantify relationships between climate and the fire regime by empirically describing both fire activity and severity along two climatic water balance gradients, actual evapotranspiration (AET) and water deficit (WD), that can be considered proxies for fuel amount and fuel moisture, respectively. We also concurrently summarize fire activity and severity among ecoregions, providing an empirically based description of the geographic distribution of fire regimes. Our results show that fire activity in the western US increases with fuel amount (represented by AET) but has a unimodal (i.e., humped) relationship with fuel moisture (represented by WD); fire severity increases with fuel amount and fuel moisture. The explicit links between fire regime components and physical environmental gradients suggest that multivariable statistical models can be generated to produce an empirically based fire regime map for the western US. Such models will potentially enable researchers to anticipate climate-mediated changes in fire recurrence and its impacts based on gridded spatial data representing future climate scenarios

Wildland fire deficit and surplus in the western United States, 1984–2012

Wildland fire is an important disturbance agent in the western US and globally. However, the natural role of fire has been disrupted in many regions due to the influence of human activities, which have the potential to either exclude or promote fire, resulting in a ‘‘fire deficit’’ or ‘‘fire surplus’’, respectively. In this study, we developed a model of expected area burned for the western US as a function of climate from 1984 to 2012.We then quantified departures from expected area burned to identify geographic regions with fire deficit or surplus. We developed our model of area burned as a function of several climatic variables from reference areas with low human influence; the relationship between climate and fire is strong in these areas. We then quantified the degree of fire deficit or surplus for all areas of the western US as the difference between expected (as predicted with the model) and observed area burned from 1984 to 2012. Results indicate that many forested areas in the western US experienced a fire deficit from 1984 to 2012, likely due to fire exclusion by human activities. We also found that large expanses of non-forested regions experienced a fire surplus, presumably due to introduced annual grasses and the prevalence of anthropogenic ignitions. The heterogeneity in patterns of fire deficit and surplus among ecoregions emphasizes fundamentally different ecosystem sensitivities to human influences and suggests that largescale adaptation and mitigation strategies will be necessary in order to restore and maintain resilient, healthy, and naturally functioning ecosystems

Wildland fire deficit and surplus in the western United States, 1984–2012

Wildland fire is an important disturbance agent in the western US and globally. However, the natural role of fire has been disrupted in many regions due to the influence of human activities, which have the potential to either exclude or promote fire, resulting in a ‘‘fire deficit’’ or ‘‘fire surplus’’, respectively. In this study, we developed a model of expected area burned for the western US as a function of climate from 1984 to 2012.We then quantified departures from expected area burned to identify geographic regions with fire deficit or surplus. We developed our model of area burned as a function of several climatic variables from reference areas with low human influence; the relationship between climate and fire is strong in these areas. We then quantified the degree of fire deficit or surplus for all areas of the western US as the difference between expected (as predicted with the model) and observed area burned from 1984 to 2012. Results indicate that many forested areas in the western US experienced a fire deficit from 1984 to 2012, likely due to fire exclusion by human activities. We also found that large expanses of non-forested regions experienced a fire surplus, presumably due to introduced annual grasses and the prevalence of anthropogenic ignitions. The heterogeneity in patterns of fire deficit and surplus among ecoregions emphasizes fundamentally different ecosystem sensitivities to human influences and suggests that largescale adaptation and mitigation strategies will be necessary in order to restore and maintain resilient, healthy, and naturally functioning ecosystems

Wildland fire deficit and surplus in the western United States, 1984-2012

Wildland fire is an important disturbance agent in the western US and globally. However, the natural role of fire has been disrupted in many regions due to the influence of human activities, which have the potential to either exclude or promote fire, resulting in a fire deficit or fire surplus, respectively. In this study, we developed a model of expected area burned for the western US as a function of climate from 1984 to 2012. We then quantified departures from expected area burned to identify geographic regions with fire deficit or surplus. We developed our model of area burned as a function of several climatic variables from reference areas with low human influence; the relationship between climate and fire is strong in these areas. We then quantified the degree of fire deficit or surplus for all areas of the western US as the difference between expected (as predicted with the model) and observed area burned from 1984 to 2012. Results indicate that many forested areas in the western US experienced a fire deficit from 1984 to 2012, likely due to fire exclusion by human activities. We also found that large expanses of non-forested regions experienced a fire surplus, presumably due to introduced annual grasses and the prevalence of anthropogenic ignitions. The heterogeneity in patterns of fire deficit and surplus among ecoregions emphasizes fundamentally different ecosystem sensitivities to human influences and suggests that large scale adaptation and mitigation strategies will be necessary in order to restore and maintain resilient, healthy, and naturally functioning ecosystems

Contrasting human influences and macro-environmental factors on fire activity inside and outside protected areas in North America

Human activities threaten the effectiveness of protected areas (PAs) in achieving their conservation goals across the globe. In this study, we contrast the influence of human and macro-environmental factors driving fire activity inside and outside PAs. Using area burned between 1984 and 2014 for 11 ecoregions in Canada and the United States, we built and compared statistical models of fire likelihood using the MaxEnt software and a set of 11 key anthropogenic, climatic, and physical variables. Overall, the full model (i.e. including all variables) performed better (adjusted area under the curve ranging from 0.71 to 0.95 for individual ecoregions) than the model that excluded anthropogenic variables. Both model types (with and without anthropogenic variables) generally performed better inside than outside the PAs. Climatic variables were usually of foremost importance in explaining fire activity inside and outside PAs, with anthropogenic variables being the second most important predictors, even inside PAs. While the individual contributions of anthropogenic variables indicate that fire activity decreased as of function of increasing human footprint, the anthropogenic effects were often substantially greater than those of physical features and were comparable to or even greater than climatic effects in some densely developed ecoregions, both outside and within PAs (e.g. Mediterranean California, Eastern Temperate Forest, and Tropical Wet Forests). Together, these results show the pervasive impact of humans on fire regimes inside PAs, as well as outside PAs. Given the increasing attractiveness of PAs, the implications for adaptive fire management beyond the concept of naturalness in the PAs are discussed. Our assessment of human-altered fire activity could serve as an indicator of human pressure in PAs; however, we suggest that further analysis is needed to understand specific interactions among fire, human pressures, and the environmental conditions at the scale of PAs

Discovering RNA-Protein Interactome by Using Chemical Context Profiling of the RNA-Protein Interface

SummaryRNA-protein (RNP) interactions generally are required for RNA function. At least 5% of human genes code for RNA-binding proteins. Whereas many approaches can identify the RNA partners for a specific protein, finding the protein partners for a specific RNA is difficult. We present a machine-learning method that scores a protein’s binding potential for an RNA structure by utilizing the chemical context profiles of the interface from known RNP structures. Our approach is applicable even when only a single RNP structure is available. We examined 801 mammalian proteins and find that 37 (4.6%) potentially bind transfer RNA (tRNA). Most are enzymes involved in cellular processes unrelated to translation and were not known to interact with RNA. We experimentally tested six positive and three negative predictions for tRNA binding in vivo, and all nine predictions were correct. Our computational approach provides a powerful complement to experiments in discovering new RNPs