Development and validation of AMANDA, a new algorithm for selecting highly relevant regions in Molecular Interaction Fields

Descriptors based on Molecular Interaction Fields (MIF) are highly suitable for drug discovery, but their size (thousands of variables) often limits their application in practice. Here we describe a simple and fast computational method that extracts from a MIF a handful of highly informative points (hot spots) which summarize the most relevant information. The method was specifically developed for drug discovery, is fast, and does not require human supervision, being suitable for its application on very large series of compounds. The quality of the results has been tested by running the method on the ligand structure of a large number of ligand-receptor complexes and then comparing the position of the selected hot spots with actual atoms of the receptor. As an additional test, the hot spots obtained with the novel method were used to obtain GRIND-like molecular descriptors which were compared with the original GRIND. In both cases the results show that the novel method is highly suitable for describing ligand-receptor interactions and compares favorably with other state-of-the-art methods.

Suitability of GRIND-based principal properties for the description of molecular similarity and ligand-based virtual screening

The information provided by the alignment-independent GRid Independent Descriptors (GRIND) can be condensed by the application of principal component analysis, obtaining a small number of principal properties (GRIND-PP), which is more suitable for describing molecular similarity. The objective of the present study is to optimize diverse parameters involved in the obtention of the GRIND-PP and validate their suitability for applications, requiring a biologically relevant description of the molecular similarity. With this aim, GRIND-PP computed with a collection of diverse settings were used to carry out ligand-based virtual screening (LBVS) on standard conditions. The quality of the results obtained was remarkable and comparable with other LBVS methods, and their detailed statistical analysis allowed to identify the method settings more determinant for the quality of the results and their optimum. Remarkably, some of these optimum settings differ significantly from those used in previously published applications, revealing their unexplored potential. Their applicability in large compound database was also explored by comparing the equivalence of the results obtained using either computed or projected principal properties. In general, the results of the study confirm the suitability of the GRIND-PP for practical applications and provide useful hints about how they should be computed for obtaining optimum results.

Y-chromosome diversity in native mexicans reveals continental transition of genetic structure in the Americas

The genetic characterization of Native Mexicans is important to understand multiethnic based features influencing the medical genetics of present Mexican populations, as well as to the reconstruct the peopling of the Americas. We describe the Y-chromosome genetic diversity of 197 Native Mexicans from 11 populations and 1,044 individuals from 44 Native American populations after combining with publicly available data. We found extensive heterogeneity among Native Mexican populations and ample segregation of Q-M242* (46%) and Q-M3 (54%) haplogroups within Mexico. The northernmost sampled populations falling outside Mesoamerica (Pima and Tarahumara) showed a clear differentiation with respect to the other populations, which is in agreement with previous results from mtDNA lineages. However, our results point toward a complex genetic makeup of Native Mexicans whose maternal and paternal lineages reveal different narratives of their population history, with sex-biased continental contributions and different admixture proportions. At a continental scale, we found that Arctic populations and the northernmost groups from North America cluster together, but we did not find a clear differentiation within Mesoamerica and the rest of the continent, which coupled with the fact that the majority of individuals from Central and South American samples are restricted to the Q-M3 branch, supports the notion that most Native Americans from Mesoamerica southwards are descendants from a single wave of migration. This observation is compatible with the idea that present day Mexico might have constituted an area of transition in the diversification of paternal lineages during the colonization of the Americas.

Signatures of selection in the human olfactory receptor OR5I1 gene

The human olfactory receptor repertoire is reduced in comparison to other mammalsand to other non-human primates. Nonetheless, this olfactory decline opens an opportunity forevolutionary innovation and improvement. In the present study, we focus on an olfactoryreceptor gene, OR5I1, which had previously been shown to present an excess of amino acidreplacement substitutions between humans and chimpanzees. We analyze the geneticvariation in OR5I1 in a large worldwide human panel and find an excess of derived allelessegregating at relatively high frequencies in all populations. Additional evidence for selectionincludes departures from neutrality in allele frequency spectra tests but no unusually extendedhaplotype structure. Moreover, molecular structural inference suggests that one of thenonsynonymous polymorphisms defining the presumably adaptive protein form of OR5I1may alter the functional binding properties of the olfactory receptor. These results arecompatible with positive selection having modeled the pattern of variation found in the OR5I1gene and with a relatively ancient, mild selective sweep predating the “Out of Africa”expansion of modern humans.

Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD

Background: It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates. Within each gene region and population we use r2 between all possible single nucleotide polymorphism (SNP) pairs as a measure of linkage disequilibrium and focus on the proportion of SNP pairs with r2 greater than 0.8.Results: Although the average r2 was found to be significantly different both between and within continental regions, a much higher proportion of r2 variance could be attributed to differences between continental regions (2.8% vs. 0.5%, respectively). Similarly, while the proportion of SNP pairs with r2 > 0.8 was significantly different across continents for all distance classes, it was generally much more homogenous within continents, except in the case of Africa and the Americas. The only isolated populations with consistently higher LD in all distance classes with respect to their continent are the Kalash (Central South Asia) and the Surui (America). Moreover, isolated populations showed only slightly higher proportions of SNP pairs with r2 > 0.8 per gene region than non-isolated populations in the same continent. Thus, the number of SNPs in isolated populations that need to be genotyped may be only slightly less than in non-isolates. Conclusion: The "isolated population" label by itself does not guarantee a greater genotyping efficiency in association studies, and properties other than increased linkage disequilibrium may make these populations interesting in genetic epidemiology.

Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

Background: Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results: This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC.Conclusion: This study proposes that variation at putative 8q24 cis-regulator(s) of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

African signatures of recent positive selection in human FOXI1

Background: The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene underhuman-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences.Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans,20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39worldwide human populations from the HGDP-CEPH diversity panel.Results: The genome sequences recently available from other primate and non-primate species showed that FOXI1divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant inEuropeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsbstatistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recentepisode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on theputatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies stronglycorrelated with the absolute geographical latitude of the populations sampled.Conclusions: We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate mightbe related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediatedwater-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.

Creación de materiales con soporte web para la mejora de la función docente de la Escuela Superior Politécnica-Universidad Pompeu Fabra

La Unidad de Apoyo a la Calidad y a la Innovación Docente de la Escuela Superior Politécnica (Universidad Pompeu Fabra) crea una Web para potenciar las experiencias innovadoras que responden a las necesidades y demandas del profesorado de la Escuela así como a las directrices del EEES. Esta Web se propone afianzar el contacto entre esta Unidad y el personal a quien ofrece sus servicios – fundamentalmente, profesorado de la ESUP- de manera muy dinámica. Quedan recogidas publicaciones, congresos, recursos metodológicos, bibliográficos, etc. En catalán, español e inglés respondiendo a la tendencia multilingüe hacía la que se dirige la UPF.

LdShake: learning design solutions sharing and co-edition

Two important challenges that teachers are currently facing are the sharing and the collaborative authoring of their learning design solutions, such as didactical units and learning materials. On the one hand, there are tools that can be used for the creation of design solutions and only some of them facilitate the co-edition. However, they do not incorporate mechanisms that support the sharing of the designs between teachers. On the other hand, there are tools that serve as repositories of educational resources but they do not enable the authoring of the designs. In this paper we present LdShake, a web tool whose novelty is focused on the combined support for the social sharing and co-edition of learning design solutions within communities of teachers. Teachers can create and share learning designs with other teachers using different access rights so that they can read, comment or co-edit the designs. Therefore, each design solution is associated to a group of teachers able to work on its definition, and another group that can only see the design. The tool is generic in that it allows the creation of designs based on any pedagogical approach. However, it can be particularized in instances providing pre-formatted designs structured according to a specific didactic method (such as Problem-Based Learning, PBL). A particularized LdShake instance has been used in the context of Human Biology studies where teams of teachers are required to work together in the design of PBL solutions. A controlled user study, that compares the use of a generic LdShake and a Moodle system, configured to enable the creation and sharing of designs, has been also carried out. The combined results of the real and controlled studies show that the social structure, and the commenting, co-edition and publishing features of LdShake provide a useful, effective and usable approach for facilitating teachers' teamwork.

Applying recommendations to aligncompetences, methodology and assessment in Telematics, Computing and Electronic Engineering courses

The alignment between competences, teaching-learning methodologies and assessment is a key element of the European Higher Education Area. This paper presents the efforts carried out by six Telematics, Computer Science and Electronic Engineering Education teachers towards achieving this alignment in their subjects. In a joint work with pedagogues, a set of recommended actions were identified. A selection of these actions were applied and evaluated in the six subjects. The cross-analysis of the results indicate that the actions allow students to better understand the methodologies and assessment planned for the subjects, facilitate (self-) regulation and increase students’ involvement in the subjects.

Neología y variedades del español: el proyecto Antenas

Reseña sobre el Proyecto Antenas, que nació a finales del 2002 bajo la coordinación del Observatorio de Neología (IULA-UPF). Consta de una red de grupos que trabajan en la detección y recopilación de neologismos para las distintas variedades geográficas del español y se propone realizar un análisis contrastivo de los diferentes mecanismos de creación léxica en estas variedades.

The role of the Teaching Quality and Innovation Support Unit in the ICT Engineering Studies at Universitat Pompeu Fabra

One of the strategies of Universitat Pompeu Fabra to support Quality Learning has been the creation of Units for the Support of Teaching Quality and Innovation within each faculty. In the seminar we will present the role and activities of the Polytechnic School Unit in charge or coordinating the efforts towards quality learning in the Information and Communication Technologies (ICT) Engineering Studies. We will also discuss how these activities are informed to relevant academic stakeholders.

Evaluación del curso de introducción a la universidad (INECE’08)

El Curso de Introducción a la Universidad (CIU) se desarrolla enla Escuela Superior Politécnica de la Universidad Pompeu Fabra con la intención de alcanzar dos objetivos: (I) ofrecer a los nuevos información sobre las características organizativas y académicas de los estudios que ofrece la Escuela e (II) introducirlos a la metodología implantada mediante el Espacio Europeo de Educación Superior (EEES) de forma participativa y activa. Para la consecución de los objetivos se plantean actividades, clases yseminarios en base a tres grandes bloques temáticos: aspectosinstitucionales, metodológicos y recursos disponibles.Se administran dos instrumentos que permiten realizar la evaluación de la organización y desarrollo de las actividades realizadas en particular, así como del curso en general. Estos resultados son analizados individual y globalmente y posteriormente se comparan con los obtenidos en el CIU 07-08.De toda esta información se extraen conclusiones del CIU a dos niveles en cuanto a la organización del mismo: por un lado se verifica la incorporación de mejoras respecto el CIU del curso pasado y, por el otro, se extraen nuevas propuestas de mejora para implementar de cara al próximo curso.

Aplicación de recomendaciones en pro de la alineación entre competencias-metodología-evaluación en asignaturas de ingeniería telemática.

Este trabajo recoge la experiencia llevada a cabo en tres asignaturas en cuanto a la aplicación de recomendaciones (acciones) dirigidas a la mejora de la alineación entre las competencias planteadas en los respectivos planes docentes, la metodología para trabajarlas y evaluación de las mismas. Concretamente las asignaturas que han puesto en marcha estas recomendaciones pertenecen a la Universidad Pompeu Fabra (una asignatura) y a la Universidad de Valladolid (las otras dos) todas pertenecientes al área de Ingeniería Telemática. Además de incluir una breve descripción de las recomendaciones aplicadas se presenta el contexto de cada caso (características básicas de las asignaturas), el proceso seguido durante su aplicación así como la evaluación llevada a cabo (tanto durante el proceso de aplicacióncomo al finalizar) para conocer el nivel de satisfacción tanto del colectivo discente como del docente. Finalmente se incluyen las reflexiones realizadas en forma de conclusiones que giran entorno a dos ejes: el primero de ellos es el impacto de la aplicación de las recomendaciones en la calidad de la función docente y el segundo hace referencia al aumento de la visibilidad de esta relación desde la perspectiva discente y las repercusiones en su proceso de aprendizaje.

La evaluación como elemento clave de la formación basada en competencias: tres casos en el ámbito de la ingenierías

El Espacio Europeo de Educación Superior implica cambios organizativos y académicos referentes a la formación basada en competencias. El proyecto AlineaME, coordinado por la Unidad de Soporte a la Calidad y la Innovación Docente de la Escuela Superior Politécnica - Universidad Pompeu Fabra, propuso a docentes del área TIC y a pedagogos la reflexión conjunta en aras a diseñar recomendaciones centradas en la alineación entre los tres elementos clave del proyecto: competencias, metodología y evaluación (C*M*E). Este trabajo recoge tres casos de aplicación de recomendaciones, concretamente de Ingeniería Telemática (dos casos - Universidad de Valladolid y Pompeu Fabra) y de Ingeniería Técnica en Informática de Gestión (un caso - Universidad de Sevilla).Las recomendaciones aplicadas hacen referencia a la necesidad de explicitar la alineación C*M*E en los Planes Docentes de Asignaturas y de presentar esta alineación al estudiantado. También a la integración de la evaluación de la asignatura como tarea-proceso de aprendizaje. La metodología seguida para laaplicación de ambas es (salvo pequeñas diferencias) parecida en los tres casos. La primera recomendación consistió en recoger en el Plan Docente la Alineación y en verbalizar dicha alineación en la sesión de presentación de la asignatura. La segunda se incorporó incluyendo actividades formativas en las que se favorecía la evaluación entre iguales. Para evaluar la aplicación de recomendaciones se recogieron evidencias en clave de satisfacción por parte del estudiantado así como valoraciones de los propios docentes. Para ello se diseñaron instrumentos específicos.En cuanto a la presentación de la alineación C*M*E en los Planes Docentes de asignaturas, los resultados indican que los alumnos son más conscientes de qué, cómo y por qué van a trabajar y ser evaluados. Globalmente valoran positivamente su utilidad para la autorregulación. Asimismo, plantear la evaluación como tarea deaprendizaje resultó ser para los estudiantes un interesante elemento de reflexión.