Papers by Elmer Fernandez
High throughput mRNA sample sequencing, known as RNA-seq, is as a powerful approach to detect dif... more High throughput mRNA sample sequencing, known as RNA-seq, is as a powerful approach to detect differentially expressed genes starting from millions of short sequence reads. Although several workflows have been proposed to analyze RNA-seq data, the experiment quality control as a whole is not usually considered, thus potentially biasing the results and/or causing information lost. Experiment quality control refers to the analysis of the experiment as a whole, prior to any analysis. It not only inspects the presence of technical effects, but also if general biological assumptions are fulfilled. In this sense, multivariate approaches are crucial for this task. Here, a multivariate approach for quality control in RNA-seq experiments is proposed. This approach uses simple and yet effective well-known statistical methodologies. In particular, Principal Component Analysis was successfully applied over real data to detect and remove outlier samples. In addition, traditional multivariate exploration tools were applied in order to asses several controls that can help to ensure the results quality. Based on differential expression and functional enrichment analysis, here is demonstrated that the information retrieval is significantly enhanced through experiment quality control. Results show that the proposed multivariate approach increases the information obtained from RNA-seq data after outlier samples removal.
Ambitious eforts to characterize the ge nomics of cancer, made by initiatives such as the Cancer... more Ambitious eforts to characterize the ge nomics of cancer, made by initiatives such as the Cancer Genome Atlas and the Global Cancer Genomics Consortium, have highlighted the disease’s complexity and exposed how far we are from understanding the intrinsic molecular mechanisms that govern cancer outcome and response to therapy (1). Many of these cost-intensive studies used cutting-edge genomic technologies
and were performed in developed countries with the support of national and regional agencies. Since then, investigators have
delved more deeply into the efects of race and ethnic origin, and their intrinsic human genetic variation, on cancer susceptibility, prognosis, and response to therapy. T us, cancer’s complexity has created a challenge that encouraged concerted international efforts to improve the capacity for excellence in translational medicine research in developing countries. This unmet need spurred the Center for Global Health of the U.S.
National Cancer Institute (NCI) to createthe U.S.–Latin America Cancer Research Network (LACRN) (table S1), with the aim
of strengthening collaborative research efforts among the participating countries, advancing translational cancer research, and reducing the global cancer burden. Here, we describe the implementation of the net work’s frst translational study on reast cancer genomics (Table 1).
Gene expression analysis does not end in a list of differentially expressed (DE) genes, but requi... more Gene expression analysis does not end in a list of differentially expressed (DE) genes, but requires a comprehensive functional analysis (FA) of the underlying molecular mechanisms. Gene Set and Singular Enrichment Analysis (GSEA and SEA) over Gene Ontology (GO) are the most used FA approaches. Several statistical methods have been developed and compared in terms of computational efficiency and/or appropriateness. However, none of them were evaluated from a biological point of view or in terms of consistency on information retrieval. In this context, questions regarding " are methods comparable? " , " is one of them preferable to the others? " , " how sensitive are they to different parameterizations? " All of them are crucial questions to face prior choosing a FA tool and they have not been, up to now, fully addressed. In this work we evaluate and compare the effect of different methods and parameters from an information retrieval point of view in both GSEA and SEA under GO. Several experiments comparing breast cancer subtypes with known different outcome (i.e. Basal-Like vs. Luminal A) were analyzed. We show that GSEA could lead to very different results according to the used statistic, model and parameters. We also show that GSEA and SEA results are fairly overlapped , indeed they complement each other. Also an integrative framework is proposed to provide complementary and a stable enrichment information according to the analyzed datasets.
J Nutr Health Aging, 2011
To assess the effectiveness of health and nutrition program (NutriAlz) versus usual care on funct... more To assess the effectiveness of health and nutrition program (NutriAlz) versus usual care on functional level in elderly people with dementia living at home, as well as on clinical practice related to nutrition and on the caregiver's burden. Cluster randomized multi-centre study with one-year follow-up. 11 Alzheimer outpatients and day care centres (Barcelona, Spain). Nine hundred and forty six home-living Alzheimer patients with identified caregiver were consecutively recruited (intervention group: 6 centres, 448 patients vs control group: 5 centres, 498 patients). The intervention was a teaching and training intervention on health and nutrition program, NutriAlz, directed both to physician and main caregiver, as well as persons affected by Alzheimer's disease or other dementias, including a standardised protocol for feeding and nutrition. The main outcome measure was the reduction in the loss of autonomy (Activities of daily living (ADL/IADL) scales) assessed at 6 and 12 months. Secondary outcomes measures were Improvement in nutritional status (Mini Nutritional Assessment (MNA), BMI, and weight changes), and caregiver burden (Zarit scale). The one-year assessment was completed for 293 patients (65.4%) in the intervention group and 363 patients (72.9%) in the control group (usual care). The annual rate of ADL change was -0.83 vs -0.62 (p=0.984), and the caregiver's subjective burden 0.59 vs 2.36 (p=0.681) in intervention and control group, respectively. MNA, however, showed an improvement (+0.46 vs -0.66, p=0.028), suggesting an effective nutritional behaviour. The NutriAlz program had no effect on functional decline in Alzheimer disease patients living at home over one year, but reduced the risk for malnutrition, as recommendations concerning diet and exercise were provided.
Molecular and Cellular Endocrinology, 2013
The aim of this study was to analyse the biological response to different recombinant human FSH (... more The aim of this study was to analyse the biological response to different recombinant human FSH (rhFSH) glycosylation variants on the endocrine activity and gene expression at whole-genome scale in human granulosa-like tumor cell line, KGN. The effects of differences in rhFSH sialylation and oligosaccharide complexity were determined on steroid hormone and inhibin production. A microarray approach was used to explore gene expression patterns induced by rhFSH glycosylation variants. Set enrichment analysis revealed that hormone sialylation and oligosaccharide complexity in rhFSH differentially affected the expression of genes involved in essential biological processes and molecular functions of KGN cells. The relevance of rhFSH oligosaccharide structure on steroidogenesis was confirmed assessing gene expression by real time-PCR. The results demonstrate that FSH oligosaccharide structure affects expression of genes encoding proteins, growth factors and hormones essential for granulosa cells function.
La posible influencia de la actividad solar sobre la salud humana a través de procesos biogeomagn... more La posible influencia de la actividad solar sobre la salud humana a través de procesos biogeomagnéticos es en la actualidad un tema de gran discusión. Algunos procesos que ocurren en el Sol pueden afectar el entorno terrestre y producir grandes perturbaciones en el campo geomagnético. El índice Dst, el cual mide un promedio de las perturbaciones del campo geomagnético en el ecuador terrestre, es un buen indicador global de estas fluctuaciones. Por otro lado, los eritrocitos, los leucocitos y las plaquetas desempeñan un rol esencial en los sistemas vivos, ya que son responsables del transporte de oxígeno, de la respuesta del sistema inmunológico y de la coagulación, respectivamente. En este trabajo se analiza la posible asociación entre el número de células sanguíneas (colectadas de dos ovejas durante 1024 días consecutivos) y el índice Dst. Se ha encontrado que la correlación cruzada entre ambas series temporales es muy baja. Sin embargo, se encuentra una correlación significativa en las amplitudes del espacio de frecuencias. La identificación y análisis de los principales picos presentes en los espectros muestra que en ambas series se encuentra presente una importante componente en 7 días.
The sequencing efforts of the past decade have not only allowed us to gain knowledge of the genom... more The sequencing efforts of the past decade have not only allowed us to gain knowledge of the genomes of hundreds of organisms -including the human genome-but have also expanded the horizons of scientific research. The logical next step after having collected the list of genes from all those genomes is to discover how these genes work in their cellular environment. As a response to this challenge, new technologies such as DNA microarrays, mass-spectrometry and fluorescent microscopy, to name a few, have been developed to study gene activity under a variety of cellular conditions. The grand-total of these new technologies along with the information-technology methodology that makes possible the analysis and interpretation of the massive amount of data that ensued, has given rise to a new sub-discipline known as functional genomics. Perhaps the most mature among the technologies used in functional genomics is that of DNA microarrays, which allow us to simultaneously measure the activity of thousands of genes. In this tutorial article we discuss the design of these devices, the challenges associated to normalization and noise-reduction that render a more precise measurement of gene expression levels, and the most popular statistical methodologies used in the data analysis. As an outcome of these efforts in functional genomics, important medical applications such as disease diagnostics, stratification of clinical cohorts and drug toxicology, among others, are now foreseeable in the near future.
The possible influence of solar activity on human health through magneto-biological mechanisms is... more The possible influence of solar activity on human health through magneto-biological mechanisms is a prominent and controversial matter. Several physical mechanisms that occur in the Sun can affect the interplanetary environment of the Earth, and produce perturbations in the geomagnetic field. The Dst index, which measures the average disturbance magnetic field at the Earth’s equator, is a good indicator of these global magnetic fluctuations. Erythrocytes, platelets and leukocytes play a key role in living systems because they are responsible for the transport of oxygen, coagulation and the immune response respectively. In the healthy subject, blood cell counts fluctuate and it is customary to talk of normal ranges or maximal limits. However, it has recently been reported that these fluctuations are scale-invariant. Daily fluctuations in the number of a given type of blood cell are expected to reflect the intrinsic dynamics of the hematologic system and its response to various intrin...
RESUMEN Uno de los objetivos más frecuentes en los análisis de expresión génica es identificar ge... more RESUMEN Uno de los objetivos más frecuentes en los análisis de expresión génica es identificar genes cuyos niveles de expresión cambian entre dos o más condiciones experimentales. Para este fin es habitual utilizar modelos paramétricos [1] o no paramétricos [2] sobre cada gen de manera independiente. Este enfoque es adecuado en diseños simples pero se vuelve insuficiente cuando el diseño experimental adquiere mayor complejidad. En este marco, los modelos mixtos se presentan como una herramienta potente y flexible para el análisis de experimentos multifactoriales complejos, como aquellos que involucran diseños desbalanceados, medidas repetidas o dependencias entre los datos. Sin embargo, los mismos presentan algunas dificultades técnicas que han complicado su uso en forma extendida. En primer lugar, los algoritmos utilizados son computacionalmente intensivos, lo cual no es despreciable cuando se deben ajustar miles de modelos en simultáneo. Además, la selección del modelo más plausib...
Lecture Notes in Computer Science, 1999
Computers in Cardiology 1996, 1996
Abstract Presents a comparison between two different methods for analyzing ischemic episodes. Bot... more Abstract Presents a comparison between two different methods for analyzing ischemic episodes. Both methods are based on a beat by beat analysis of a large number of parameters. The authors process these data in order to extract information regarding the detection of meaningful cycles (presumably related to ischemic episodes) on ECG parameter evolution. In order to facilitate visual inspection of parameter evolution and thus facilitate the definition of criteria to detect such meaningful cycles, the authors apply a ...
Neuropharmacology, 2015
Whether the treatment of Parkinson&am... more Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets.
Lecture Notes in Computer Science, 2012
The tree architecture has been employed to solve multi-class problems based on SVM. It is an alte... more The tree architecture has been employed to solve multi-class problems based on SVM. It is an alternative to the well known OVO/OVA strategies. Most of the tree base SVM classifiers try to split the multi-class space, mostly, by some clustering like algorithms into several binary partitions. One of the main drawbacks of this is that the natural class structure is not taken into account. Also the same SVM parameterization is used for all classifiers. Here a preliminary and promising result of a multi-class space partition method that account for data base class structure and allow node's parameter specific solutions is presented. In each node the space is split into two class problem possibilities and the best SVM solution found. Preliminary results show that accuracy is improved, lesser information is required, each node reaches specific cost values and hard separable classes can easily be identified.
El control de calidad es una etapa fundamental para remover artefactos técnicos en datos de expre... more El control de calidad es una etapa fundamental para remover artefactos técnicos en datos de expresión de genes obtenidos a través de microarreglos de ADN. Los abordajes tradicionales sólo emplean estrategias univariadas, con el fin de comprobar el supuesto de normalidad global de los genes, al igual que para obtener valores de expresión comparables entre las diferentes muestras. No obstante, los anteriores presentan dos falencias: i) no incluyen la información del diseño experimental en el control de calidad; ii) la exploración de los genes se realiza de forma univariada. En este contexto, se presenta como alternativa para el control de calidad, descomponer los valores observados de expresión utilizando la información del diseño experimental a través de un análisis de la varianza (ANOVA). Luego, la contribución de los diferentes factores puede ser analizada de forma multivariada mediante dos técnicas de exploración como los son el Análisis de Componentes Principales (PCA por sus siglas en inglés) y la regresión de Mínimos Cuadrados Parciales (PLS por sus siglas en inglés). La estrategia propuesta ha sido aplicada con éxito sobre un experimento de microarreglos de dos factores. Con ella se ha logrado detectar y remover artefactos no considerados en el diseño experimental, que no pudieron ser detectados ni removidos por los abordajes tradicionales.
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Papers by Elmer Fernandez
and were performed in developed countries with the support of national and regional agencies. Since then, investigators have
delved more deeply into the efects of race and ethnic origin, and their intrinsic human genetic variation, on cancer susceptibility, prognosis, and response to therapy. T us, cancer’s complexity has created a challenge that encouraged concerted international efforts to improve the capacity for excellence in translational medicine research in developing countries. This unmet need spurred the Center for Global Health of the U.S.
National Cancer Institute (NCI) to createthe U.S.–Latin America Cancer Research Network (LACRN) (table S1), with the aim
of strengthening collaborative research efforts among the participating countries, advancing translational cancer research, and reducing the global cancer burden. Here, we describe the implementation of the net work’s frst translational study on reast cancer genomics (Table 1).
and were performed in developed countries with the support of national and regional agencies. Since then, investigators have
delved more deeply into the efects of race and ethnic origin, and their intrinsic human genetic variation, on cancer susceptibility, prognosis, and response to therapy. T us, cancer’s complexity has created a challenge that encouraged concerted international efforts to improve the capacity for excellence in translational medicine research in developing countries. This unmet need spurred the Center for Global Health of the U.S.
National Cancer Institute (NCI) to createthe U.S.–Latin America Cancer Research Network (LACRN) (table S1), with the aim
of strengthening collaborative research efforts among the participating countries, advancing translational cancer research, and reducing the global cancer burden. Here, we describe the implementation of the net work’s frst translational study on reast cancer genomics (Table 1).