Ecological models at fish community and species level to support effective river restoration

RESUMEN Los peces nativos son indicadores de la salud de los ecosistemas acuáticos, y se han convertido en un elemento de calidad clave para evaluar el estado ecológico de los ríos. La comprensión de los factores que afectan a las especies nativas de peces es importante para la gestión y conservación de los ecosistemas acuáticos. El objetivo general de esta tesis es analizar las relaciones entre variables biológicas y de hábitat (incluyendo la conectividad) a través de una variedad de escalas espaciales en los ríos Mediterráneos, con el desarrollo de herramientas de modelación para apoyar la toma de decisiones en la restauración de ríos. Esta tesis se compone de cuatro artículos. El primero tiene como objetivos modelar la relación entre un conjunto de variables ambientales y la riqueza de especies nativas (NFSR), y evaluar la eficacia de potenciales acciones de restauración para mejorar la NFSR en la cuenca del río Júcar. Para ello se aplicó un enfoque de modelación de red neuronal artificial (ANN), utilizando en la fase de entrenamiento el algoritmo Levenberg-Marquardt. Se aplicó el método de las derivadas parciales para determinar la importancia relativa de las variables ambientales. Según los resultados, el modelo de ANN combina variables que describen la calidad de ribera, la calidad del agua y el hábitat físico, y ayudó a identificar los principales factores que condicionan el patrón de distribución de la NFSR en los ríos Mediterráneos. En la segunda parte del estudio, el modelo fue utilizado para evaluar la eficacia de dos acciones de restauración en el río Júcar: la eliminación de dos azudes abandonados, con el consiguiente incremento de la proporción de corrientes. Estas simulaciones indican que la riqueza aumenta con el incremento de la longitud libre de barreras artificiales y la proporción del mesohabitat de corriente, y demostró la utilidad de las ANN como una poderosa herramienta para apoyar la toma de decisiones en el manejo y restauración ecológica de los ríos Mediterráneos. El segundo artículo tiene como objetivo determinar la importancia relativa de los dos principales factores que controlan la reducción de la riqueza de peces (NFSR), es decir, las interacciones entre las especies acuáticas, variables del hábitat (incluyendo la conectividad fluvial) y biológicas (incluidas las especies invasoras) en los ríos Júcar, Cabriel y Turia. Con este fin, tres modelos de ANN fueron analizados: el primero fue construido solamente con variables biológicas, el segundo se construyó únicamente con variables de hábitat y el tercero con la combinación de estos dos grupos de variables. Los resultados muestran que las variables de hábitat son los ¿drivers¿ más importantes para la distribución de NFSR, y demuestran la importancia ecológica de los modelos desarrollados. Los resultados de este estudio destacan la necesidad de proponer medidas de mitigación relacionadas con la mejora del hábitat (incluyendo la variabilidad de caudales en el río) como medida para conservar y restaurar los ríos Mediterráneos. El tercer artículo busca comparar la fiabilidad y relevancia ecológica de dos modelos predictivos de NFSR, basados en redes neuronales artificiales (ANN) y random forests (RF). La relevancia de las variables seleccionadas por cada modelo se evaluó a partir del conocimiento ecológico y apoyado por otras investigaciones. Los dos modelos fueron desarrollados utilizando validación cruzada k-fold y su desempeño fue evaluado a través de tres índices: el coeficiente de determinación (R2 ), el error cuadrático medio (MSE) y el coeficiente de determinación ajustado (R2 adj). Según los resultados, RF obtuvo el mejor desempeño en entrenamiento. Pero, el procedimiento de validación cruzada reveló que ambas técnicas generaron resultados similares (R2 = 68% para RF y R2 = 66% para ANN). La comparación de diferentes métodos de machine learning es muy útil para el análisis crítico de los resultados obtenidos a través de los modelos. El cuarto artículo tiene como objetivo evaluar la capacidad de las ANN para identificar los factores que afectan a la densidad y la presencia/ausencia de Luciobarbus guiraonis en la demarcación hidrográfica del Júcar. Se utilizó una red neuronal artificial multicapa de tipo feedforward (ANN) para representar relaciones no lineales entre descriptores de L. guiraonis con variables biológicas y de hábitat. El poder predictivo de los modelos se evaluó con base en el índice Kappa (k), la proporción de casos correctamente clasificados (CCI) y el área bajo la curva (AUC) característica operativa del receptor (ROC). La presencia/ausencia de L. guiraonis fue bien predicha por el modelo ANN (CCI = 87%, AUC = 0.85 y k = 0.66). La predicción de la densidad fue moderada (CCI = 62%, AUC = 0.71 y k = 0.43). Las variables más importantes que describen la presencia/ausencia fueron: radiación solar, área de drenaje y la proporción de especies exóticas de peces con un peso relativo del 27.8%, 24.53% y 13.60% respectivamente. En el modelo de densidad, las variables más importantes fueron el coeficiente de variación de los caudales medios anuales con una importancia relativa del 50.5% y la proporción de especies exóticas de peces con el 24.4%. Los modelos proporcionan información importante acerca de la relación de L. guiraonis con variables bióticas y de hábitat, este nuevo conocimiento podría utilizarse para apoyar futuros estudios y para contribuir en la toma de decisiones para la conservación y manejo de especies en los en los ríos Júcar, Cabriel y Turia.Olaya Marín, EJ. (2013). Ecological models at fish community and species level to support effective river restoration [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/28853TESI

A Latent Parameter Node-Centric Model for Spatial Networks

Spatial networks, in which nodes and edges are embedded in space, play a vital role in the study of complex systems. For example, many social networks attach geo-location information to each user, allowing the study of not only topological interactions between users, but spatial interactions as well. The defining property of spatial networks is that edge distances are associated with a cost, which may subtly influence the topology of the network. However, the cost function over distance is rarely known, thus developing a model of connections in spatial networks is a difficult task. In this paper, we introduce a novel model for capturing the interaction between spatial effects and network structure. Our approach represents a unique combination of ideas from latent variable statistical models and spatial network modeling. In contrast to previous work, we view the ability to form long/short-distance connections to be dependent on the individual nodes involved. For example, a node's specific surroundings (e.g. network structure and node density) may make it more likely to form a long distance link than other nodes with the same degree. To capture this information, we attach a latent variable to each node which represents a node's spatial reach. These variables are inferred from the network structure using a Markov Chain Monte Carlo algorithm. We experimentally evaluate our proposed model on 4 different types of real-world spatial networks (e.g. transportation, biological, infrastructure, and social). We apply our model to the task of link prediction and achieve up to a 35% improvement over previous approaches in terms of the area under the ROC curve. Additionally, we show that our model is particularly helpful for predicting links between nodes with low degrees. In these cases, we see much larger improvements over previous models

Structural Prediction of Protein–Protein Interactions by Docking: Application to Biomedical Problems

A huge amount of genetic information is available thanks to the recent advances in sequencing technologies and the larger computational capabilities, but the interpretation of such genetic data at phenotypic level remains elusive. One of the reasons is that proteins are not acting alone, but are specifically interacting with other proteins and biomolecules, forming intricate interaction networks that are essential for the majority of cell processes and pathological conditions. Thus, characterizing such interaction networks is an important step in understanding how information flows from gene to phenotype. Indeed, structural characterization of protein–protein interactions at atomic resolution has many applications in biomedicine, from diagnosis and vaccine design, to drug discovery. However, despite the advances of experimental structural determination, the number of interactions for which there is available structural data is still very small. In this context, a complementary approach is computational modeling of protein interactions by docking, which is usually composed of two major phases: (i) sampling of the possible binding modes between the interacting molecules and (ii) scoring for the identification of the correct orientations. In addition, prediction of interface and hot-spot residues is very useful in order to guide and interpret mutagenesis experiments, as well as to understand functional and mechanistic aspects of the interaction. Computational docking is already being applied to specific biomedical problems within the context of personalized medicine, for instance, helping to interpret pathological mutations involved in protein–protein interactions, or providing modeled structural data for drug discovery targeting protein–protein interactions.Spanish Ministry of Economy grant number BIO2016-79960-R; D.B.B. is supported by a predoctoral fellowship from CONACyT; M.R. is supported by an FPI fellowship from the Severo Ochoa program. We are grateful to the Joint BSC-CRG-IRB Programme in Computational Biology.Peer ReviewedPostprint (author's final draft

Systems biology in animal sciences

Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed ‘omics’ technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A ‘system’ approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with ‘system approaches’ in animal sciences, providing exciting opportunities to predict and modulate animal traits

Evaluation of protein surface roughness index using its heat denatured aggregates

Recent research works on potential of different protein surface describing parameters to predict protein surface properties gained significance for its possible implication in extracting clues on protein's functional site. In this direction, Surface Roughness Index, a surface topological parameter, showed its potential to predict SCOP-family of protein. The present work stands on the foundation of these works where a semi-empirical method for evaluation of Surface Roughness Index directly from its heat denatured protein aggregates (HDPA) was designed and demonstrated successfully. The steps followed consist, the extraction of a feature, Intensity Level Multifractal Dimension (ILMFD) from the microscopic images of HDPA, followed by the mapping of ILMFD into Surface Roughness Index (SRI) through recurrent backpropagation network (RBPN). Finally SRI for a particular protein was predicted by clustering of decisions obtained through feeding of multiple data into RBPN, to obtain general tendency of decision, as well as to discard the noisy dataset. The cluster centre of the largest cluster was found to be the best match for mapping of Surface Roughness Index of each protein in our study. The semi-empirical approach adopted in this paper, shows a way to evaluate protein's surface property without depending on its already evaluated structure

Hot-spot analysis for drug discovery targeting protein-protein interactions

Introduction: Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.This work has been funded by grants BIO2016-79930-R and SEV-2015-0493 from the Spanish Ministry of Economy, Industry and Competitiveness, and grant EFA086/15 from EU Interreg V POCTEFA. M Rosell is supported by an FPI fellowship from the Severo Ochoa program. The authors are grateful for the support of the the Joint BSC-CRG-IRB Programme in Computational Biology.Peer ReviewedPostprint (author's final draft