Annotation-Agnostic Differential Expression and Binding Analyses

My thesis work is centered around the development of R software packages for analyzing RNA sequencing (RNA-seq) and ChIP sequencing (ChIP-seq) high throughput genomic data. Chapter 2 describes the derfinder Bioconductor package which implements the DER Finder approach for identifying differentially expressed regions with RNA-seq data in an annotation-agnostic manner. Chapter 3 shows how derfinder can be applied to ChIP-seq data to identify differentially bounded regions. Chapter 4 describes the regionReport Bioconductor package for producing HTML or PDF reports from region-based genomic analyses, such as the derfinder analyses described in the previous chapters

Improving the value of public RNA-seq expression data by phenotype prediction.

Publicly available genomic data are a valuable resource for studying normal human variation and disease, but these data are often not well labeled or annotated. The lack of phenotype information for public genomic data severely limits their utility for addressing targeted biological questions. We develop an in silico phenotyping approach for predicting critical missing annotation directly from genomic measurements using well-annotated genomic and phenotypic data produced by consortia like TCGA and GTEx as training data. We apply in silico phenotyping to a set of 70 000 RNA-seq samples we recently processed on a common pipeline as part of the recount2 project. We use gene expression data to build and evaluate predictors for both biological phenotypes (sex, tissue, sample source) and experimental conditions (sequencing strategy). We demonstrate how these predictions can be used to study cross-sample properties of public genomic data, select genomic projects with specific characteristics, and perform downstream analyses using predicted phenotypes. The methods to perform phenotype prediction are available in the phenopredict R package and the predictions for recount2 are available from the recount R package. With data and phenotype information available for 70,000 human samples, expression data is available for use on a scale that was not previously feasible

Chloroplasts morphology investigation with diverse microscopy approaches and inter-specific variation in Laurencia species (Rhodophyta)

The present study described with different microscopy approaches chloroplasts lobes in Laurencia sensu latu (Rhodophyta) species and found inter-specific differences among them. Chloroplasts were investigated using confocal laser scanning microscopy (LSM), transmission electron microscopy (TEM) and high resolution scanning electron microscopy (HRSEM). Using and TEM and HRSEM images we distinguished chloroplasts with lobes than chloroplasts without lobes in Yuzurua poiteaui var. gemmifera (Harvey) M. J. Wynne and Laurencia dendroidea J. Agardh cortical cells. The LSM images showed chloroplasts lobes (CLs) with different morphologies, varying from thicker and longer undulated projections in Y. poiteaui var. and L. dendroidea to very small and thin tubules as in Laurencia translucida Fujii & Cordeiro-Marino. The diameter and length of CLs from Y poiteaui var. and L. dendroidea were significantly higher than L. translucida CLs (p \u3c 0.01). Based on LSM observations, we suggest that lobes morphology has a taxonomic validity only to characterize L. translucida species

escheR: unified multi-dimensional visualizations with Gestalt principles

SUMMARY: The creation of effective visualizations is a fundamental component of data analysis. In biomedical research, new challenges are emerging to visualize multi-dimensional data in a 2D space, but current data visualization tools have limited capabilities. To address this problem, we leverage Gestalt principles to improve the design and interpretability of multi-dimensional data in 2D data visualizations, layering aesthetics to display multiple variables. The proposed visualization can be applied to spatially-resolved transcriptomics data, but also broadly to data visualized in 2D space, such as embedding visualizations. We provide an open source R package escheR, which is built off of the state-of-the-art ggplot2 visualization framework and can be seamlessly integrated into genomics toolboxes and workflows. AVAILABILITY AND IMPLEMENTATION: The open source R package escheR is freely available on Bioconductor (https://bioconductor.org/packages/escheR)

Variables socioeconómicas influyentes en los modelos de desarrollo de Singapur y Panamá

The study seeks to differentiate between the economic development model of Singapore and that of Panama. Its importance lies in determining the macroeconomic variables that comprise GDP, the inflation rate, foreign direct investment, and employment, in which Singapore obtains more significant levels than Panama. The behavior of Singapore's economy since the 1960s has been growing and constant. Education was a determining factor in its model of economic development. The use of a Confucian philosophy constituted the ideological philosophical model that united Singapore's society, establishing long-term objectives and an indissoluble unity in government policies from 1965 to the present. In the ideological model of Panama, an ideological and integrating factor of society was not observed. In this comparative study, one impact-determining variable was observed: The Confucian philosophy linked to the educational model, which helped to further enhance the economic development of Singapore.El estudio busca establecer diferenciación entre el modelo de desarrollo económico de Singapur y el de Panamá. Su importancia radica en determinar las variables causales de la disimilitud. Los resultados más importantes del estudio se basan en variables macroeconómicas que comprenden el PIB, la tasa de inflación, la inversión extrajera directa y el empleo, en las que Singapur obtiene niveles más significativos que el de Panamá. El comportamiento de la economía de Singapur, a partir de los años sesenta, ha sido creciente y constante. La educación fue un factor determinante en su modelo de desarrollo económico. El uso de una filosofía confuciana constituyó el factor filosófico ideológico que cohesionó a la sociedad de Singapur estableciéndose objetivos a largo plazo y una unidad indisoluble en las políticas de gobierno desde el año 1965 hasta la fecha. En el modelo de desarrollo económico de Panamá, no se observó un factor ideológico e integrador de la sociedad. En este estudio comparativo se observó una variable determinante de impacto: la filosofía confuciana vinculada al modelo educativo la cual coadyuvó a potenciar aún más el desarrollo económico de Singapur. &nbsp

IntroVerse: a comprehensive database of introns across human tissues

Dysregulation of RNA splicing contributes to both rare and complex diseases. RNA-sequencing data from human tissues has shown that this process can be inaccurate, resulting in the presence of novel introns detected at low frequency across samples and within an individual. To enable the full spectrum of intron use to be explored, we have developed IntroVerse, which offers an extensive catalogue on the splicing of 332,571 annotated introns and a linked set of 4,679,474 novel junctions covering 32,669 different genes. This dataset has been generated through the analysis of 17,510 human control RNA samples from 54 tissues provided by the Genotype-Tissue Expression Consortium. IntroVerse has two unique features: (i) it provides a complete catalogue of novel junctions and (ii) each novel junction has been assigned to a specific annotated intron. This unique, hierarchical structure offers multiple uses, including the identification of novel transcripts from known genes and their tissue-specific usage, and the assessment of background splicing noise for introns thought to be mis-spliced in disease states. IntroVerse provides a user-friendly web interface and is freely available at https://rytenlab.com/browser/app/introverse

Radiosensibilidad in vitro de dos tipos de explante de frijol común cultivar 'BAT-93'

The use of Gamma radiations combined with in vitro tissue culture is a useful tool in breeding programs. However, for its application it is necessary to have an efficient plant regeneration system. The objective of this work was to determine the in vitro radiosensitivity of two types of explant of common bean (Phaseolus vulgaris L.) cultivar 'BAT-93' to Gamma radiations. Two-month harvested seeds and the cotyledonal node were irradiated with two cotyledons (NC-2), with doses of 50 and 80 Gy. As control, 100 non-irradiated seeds were used. It was evaluated the germination percentage of the irradiated seeds, the explants with callus and the number of shoots per callus at 21 days of culture in the culture media for formation and regeneration of callus, respectively. It was found that the type of explant and the radiation dose influenced the formation of calli and the shoots regeneration. From the irradiated seeds, callus was formed with the two doses of Gamma radiation used. However, the shoots regeneration just was achieved with the dose of 50 Gy. In the NC-2 explant, callus was not formed with the radiation doses used. The seed is the explant that is recommended for the application of Gamma radiations combined with the regeneration of plants via indirect organogenesis in Phaseolus vulgaris L. cultivar 'BAT 93'.Keywords: in vitro culture, cotyledonary node, mutagenesis, Phaseolus vulgaris L., seedsEl empleo de radiaciones Gamma combinadas con el cultivo de tejidos in vitro es una herramienta útil en los programas de mejoramiento genético. Sin embargo, para su aplicación es necesario disponer de un sistema de regeneración eficiente de plantas. El presente trabajo tuvo como objetivo determinar la radiosensibilidad in vitro de dos tipos de explante de frijol común (Phaseolus vulgaris L.) cultivar 'BAT-93' alas radiaciones Gamma. Se irradiaron semillas de dos meses de cosechadas y el nudo cotiledonal con dos cotiledones (NC-2), con dosis de 50 y 80 Gy. Como control se emplearon 100 semillas sin irradiar. Se evaluó el porcentaje de germinación de las semillas irradiadas, los de explantes con callo y número de brotes por callo a los 21 días de cultivo en los medios de cultivo de formación y regeneración de callos, respectivamente. Se encontró que el tipo de explante y la dosis de radiación influyeron en la formación de callos y la regeneración de brotes. De las semillas irradiadas se formaron callos con las dos dosis de radiaciones Gamma utilizadas. Sin embargo, solo se logró la regeneración de brotes con la dosis de 50 Gy. En el explante NC-2 no se formó callo con las dosis de radiación utilizadas. La semilla es el explante que se recomienda para la aplicación de radiaciones Gamma combinado con la regeneración de plantas vía organogénesis indirecta en Phaseolus vulgaris L. cultivar 'BAT 93'. Palabras clave: cultivo in vitro, nudo cotiledonal, mutagénesis, Phaseolus vulgaris L., semilla

Diferenciación de la respuesta in vitro de Phaseolus vulgaris cv. ‘ICA Pijao’ y cv. ‘Tío Canela- 75’ a altas temperaturas

 To develop an in vitro selection protocol, it is necessary to differentiate between tolerant and susceptible cultivars to the studied factor. The present work was carried out with the objective of selecting the temperature that allows to in vitro differentiating the response of the Phaseolus vulgaris cultivars 'ICA Pijao' (susceptible) and 'Tío Canela-75' (tolerant) to high temperatures. Different temperatures (30, 35, 40, 45 and 50 ºC) were applied to seeds of the two cultivars. In vitro seed germination percentage, radicle and plumule length, number of explants that formed callus and number of shoots per callus were evaluated. It was possible to differentiate between cv. ‘ICA Pijao’ (susceptible) and ‘Tío Canela- 75’ (tolerant) with the variables radicle length, plumule length, percentage of calli formed and number of regenerated shoots. It was selected 35 °C as the selective agent.Para desarrollar un protocolo de selección in vitro se hace necesario lograr la diferenciación entre cultivares tolerantes y susceptibles al factor estudiado. El presente trabajo se realizó con el objetivo de seleccionar la temperatura que permita diferenciar in vitro la respuesta de los cultivares de Phaseolus vulgaris ‘ICA Pijao’ (susceptible) y ‘Tío Canela- 75’  (tolerante) a altas temperaturas. Se aplicaron diferentes temperatura (30, 35, 40, 45 y 50 ºC) a semillas de los  dos cultivares. Se evaluó in vitro, el porcentaje de germinación de las semillas, longitud de la radícula y la plúmula, número de explantes que formaron callos y número de brotes por callo.  Se logró diferenciar entre el cv. ‘ICA Pijao’ (susceptible) y ‘Tío Canela- 75’ (Tolerante) con las variables longitud de la radícula, longitud de la plúmula, porcentaje de callos formados y número de brotes regenerados.  Se seleccionó 35 ºC como agente selectivo

The PHQ-PD as a screening tool for panicdisorder in theprimarcarsetting in Spain.

INTRODUCTION Panic disorder is a common anxiety disorder and is highly prevalent in Spanish primary care centres. The use of validated tools can improve the detection of panic disorder in primary care populations, thus enabling referral for specialized treatment. The aim of this study is to determine the accuracy of the Patient Health Questionnaire-Panic Disorder (PHQ-PD) as a screening and diagnostic tool for panic disorder in Spanish primary care centres. METHOD We compared the psychometric properties of the PHQ-PD to the reference standard, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interview. General practitioners referred 178 patients who completed the entire PHQ test, including the PHQ-PD, to undergo the SCID-I. The sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of the PHQ-PD were assessed. RESULTS The operating characteristics of the PHQ-PD are moderate. The best cut-off score was 5 (sensitivity .77, specificity .72). Modifications to the questionnaire's algorithms improved test characteristics (sensitivity .77, specificity .72) compared to the original algorithm. The screening question alone yielded the highest sensitivity score (.83). CONCLUSION Although the modified algorithm of the PHQ-PD only yielded moderate results as a diagnostic test for panic disorder, it was better than the original. Using only the first question of the PHQ-PD showed the best psychometric properties (sensitivity). Based on these findings, we suggest the use of the screening questions for screening purposes and the modified algorithm for diagnostic purposes