Gene selection and classification of microarray data using random forest

BACKGROUND: Selection of relevant genes for sample classification is a common task in most gene expression studies, where researchers try to identify the smallest possible set of genes that can still achieve good predictive performance (for instance, for future use with diagnostic purposes in clinical practice). Many gene selection approaches use univariate (gene-by-gene) rankings of gene relevance and arbitrary thresholds to select the number of genes, can only be applied to two-class problems, and use gene selection ranking criteria unrelated to the classification algorithm. In contrast, random forest is a classification algorithm well suited for microarray data: it shows excellent performance even when most predictive variables are noise, can be used when the number of variables is much larger than the number of observations and in problems involving more than two classes, and returns measures of variable importance. Thus, it is important to understand the performance of random forest with microarray data and its possible use for gene selection. RESULTS: We investigate the use of random forest for classification of microarray data (including multi-class problems) and propose a new method of gene selection in classification problems based on random forest. Using simulated and nine microarray data sets we show that random forest has comparable performance to other classification methods, including DLDA, KNN, and SVM, and that the new gene selection procedure yields very small sets of genes (often smaller than alternative methods) while preserving predictive accuracy. CONCLUSION: Because of its performance and features, random forest and gene selection using random forest should probably become part of the "standard tool-box" of methods for class prediction and gene selection with microarray data

Exploring the mechanical response of low-carbon soil improvement mixtures

As society moves towards decarbonisation, it is important to assess the hydromechanical behaviour of binders that could offer a low-carbon alternative to Portland cement in ground improvement technologies. This work considers two such alternatives: one still largely unexplored (metakaolin-based geopolymers) and a better known one (colloidal silica). Results from unconfined compressive strength, permeability tests, undrained monotonic and cyclic triaxial tests on granular soils (sand and silty sand) treated with those two binders are presented and discussed, emphasizing similarities and differences with the response of similar soils treated with other conventional and unconventional binders. Effects of silt content, curing conditions and soil/binder ratios are examined. Both colloidal silica and metakaolin-based geopolymer significantly improve the mechanical properties of the treated soils, although the geopolymer results in a stronger and stiffer material. Both treatments reduce much the permeability of the treated soil, but the reduction achieved with colloidal silica is larger.Peer ReviewedPostprint (author's final draft

Knapping on the hill: A lithic workshop site of hunter-gatherer groups from Tierra del Fuego island

6 páginas, 3 figuras.-- et al.[EN]: This paper provides the initial results obtained from the analysis of a lithic workshop, named Altos del Varela I, located on the top of Petersen hill in Tierra del Fuego Island (Argentina). The site contains distinctive areas entirely composed of a high frequency of flakes made from local metamorphic rhyolite. These results open the debate about the use of mountain landscape between the fuegian hunter-gatherers as well as the interaction between coastal and inland groups.[ES]: En este trabajo se presentan los resultados iniciales obtenidos del análisis de un taller lítico, denominado Altos del Varela I, ubicado en la cima del cerro Petersen en la isla Grande de Tierra del Fuego (Argentina). El sitio presenta diferentes áreas que incluyen, de manera exclusiva, una alta frecuencia de lascas de riolitas metamorfizadas de origen local. Los resultados permiten abrir el debate sobre el uso de los paisajes montañosos por parte de las sociedades cazadoras-recolectoras fueguinas así como sobre la interacción costa-interior.Este proyecto fue financiado por un subsidio de la Agencia Nacional de Promoción Científica y Tecnológica (PICT 2071).Peer reviewe

Determinación de un modelo para medir la productividad para una empresa productora de palmito ubicada en el cantón de San Miguel de los Bancos. Caso: “La Rogelia”

El palmito es un delicioso producto gourmet que se produce en el Ecuador y que tiene una gran demanda a nivel mundial por su excelente calidad. El objetivo del caso de estudio es medir la productividad de “La Rogelia” y de este modo proponer estrategias de mejora en la empresa así como determinar un modelo de productividad que se pueda aplicar para empresas similares. Para realizar el estudio se tomó en consideración los balances de los años 2011 y 2012 así como el proyectado que se realizó para el 2012, los balances y estados de resultados fueron elaborados durante el estudio con la información brindada por los accionistas de la mencionada empresa. Adicionalmente se realizó una visita de campo para poder obtener datos como cantidades de producción y tiempos. Una vez analizados los 10 modelos de productividad propuestos y en base a una matriz de ponderación conjuntamente analizada con los accionistas de “La Rogelia” se determinó que los modelos que aplican para este tipo de empresas son Kurosawa y el DEA, por lo que se elaboró los formatos respectivos para cada uno de ellos con el fin que puedan ser aplicados por cualquier otra empresa del medio. A la par se identificaron los factores que pueden mejorar el proceso productivo y son: el uso de la inclinación de los suelos para lograr un mejor y más rápido crecimiento del palmito, y por otro lado utilizar mejor maquinaria para realizar las labores culturales ya que así se logrará ahorrar mucho tiempo que los trabajadores podrían ocupar en otras actividades

Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer

Background: In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies. Methods: We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls. Results: We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines. Conclusions: Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient’s progression and therapeutic response.The study was financially supported by FIS (ISCIII) and ERDF/FSE funds (PI15/00186, PI18/0050, and ERDF/FSE, A way to make Europe). The authors gratefully acknowledge the Colombian Ministry for Science, Technology and Innovation (MINCIENCIAS), Code 568-2012, for providing J.S. with partial funding for this study

Efficacy and Safety of Reslizumab in Patients with Severe Asthma with Inadequate Response to Omalizumab : A Multicenter, Open-Label Pilot Study

Funding: This study was endorsed by the Asthma Research Program of the Spanish Respiratory Society (PII de Asma de SEPAR) supported by a grant from Teva Pharmaceutical Industries.Background: Patients with severe allergic and eosinophilic asthma could qualify for different biologic therapies. Objective: To evaluate the efficacy and safety of weight-based intravenous reslizumab dosing in patients who have previously failed therapy with omalizumab. Methods: We carried out a 24-week prospective, multicenter, open-label, single-group, self-controlled study in patients with severe eosinophilic asthma who had previously failed to respond to omalizumab. The main objective was to determine whether treatment with reslizumab significantly improved asthma symptoms assessed by the Asthma Control Test (ACT) at week 24. Secondary objectives were to evaluate symptoms at weeks 4 and 12, change in FEV at week 24, and the incidence of severe exacerbations over the study period. Results: Twenty-nine patients (62.1% women, median age, 50.8 years) were included in the study. The median ACT score significantly increased from 13.0 (interquartile range, 8.0-18.0) at baseline to 21.0 (interquartile range, 14.0-24.0) at 24 weeks (P =.002). Only 2 of 29 patients developed at least 1 severe exacerbation during follow-up and none of them required hospitalization. Overall, 15 of 25 patients (60%) were considered as being controlled (ACT score of ≥20 and no exacerbations) at week 24. The percentage of patients who were receiving daily systemic corticosteroids significantly decreased from 72.4% to 52.0% (P =.019). Adverse events were mostly moderate and within the range of previously reported side effects with reslizumab. Conclusion: Reslizumab is an effective and safe option for patients with severe eosinophilic asthma and a history of omalizumab failure

Transmissibility, hospitalization, and intensive care admissions due to omicron compared to delta variants of SARS-CoV-2 in Catalonia: A cohort study and ecological analysis

The transmissibility of omicron using variant screening data from primary care practices (PCP) and hospital admissions. In addition, we used this data from PCP to establish the two periods when delta and omicron were, respectively, dominant (above 95% of cases). After that, we performed a population-based cohort analysis to calculate the rates of hospital and intensive care unit (ICU) admissions for both periods and to estimate reduction in severity. Rate ratios (RR) and 95% confidence intervals (95% CI) were calculated and stratified by age and vaccination status. In a second analysis, the differential substitution model in primary care vs. hospitals allowed us to obtain a population-level average change in severity.We have included 48,874 cases during the delta period and 560,658 during the omicron period. During the delta period, on average, 3.8% of the detected cases required hospitalization for COVID-19. This percentage dropped to 0.9% with omicron [RR of 0.46 (95% CI: 0.43 to 0.49)]. For ICU admissions, it dropped from 0.8 to 0.1% [RR 0.25 (95% CI: 0.21 to 0.28)]. The proportion of cases hospitalized or admitted to ICU was lower in the vaccinated groups, independently of the variant. Omicron was associated with a reduction in risk of admission to hospital and ICU in all age and vaccination status strata. The differential substitution models showed an average RR between 0.19 and 0.50.Both independent methods consistently show an important decrease in severity for omicron relative to delta. The systematic reduction happens regardless of age. The severity is also reduced for non-vaccinated and vaccinated groups, but it remains always higher in the non-vaccinated population. This suggests an overall reduction in severity, which could be intrinsic to the omicron variant. The fact is that the RR in ICU admission is systematically smaller than in hospitalization points in the same direction.MC received funding from la Caixa Foundation ID 100010434, under agreement LCF/PR/GN17/50300003. MC, CP, and SA received funding from Ministerio de Ciencia, Innovación y Universidades and FEDER, with the project PGC2018-095456- B-I00.Objectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

CONSTRUCTION OF A CURRENT-FED PUSH-PULL CONVERTER: PRACTICAL CONSIDERATIONS (CONSTRUCCION DE UN CONVERTIDOR PUSH-PULL ALIMENTADO EN CORRIENTE: CONSIDERACIONES PRÁCTICAS)

ResumenEn este trabajo se abordan los aspectos a tener en consideración para la construcción de un convertidor Push-Pull alimentado en corriente. Cuando se va a implementar un convertidor es común encontrar suficiente bibliografía sobre el funcionamiento del convertidor Push-Pull alimentado en corriente y el dimensionamiento de sus elementos. Sin embargo, cuando en la etapa de implementación física surgen ciertos retos que no se consideran en el diseño y de los cuales no existe abundante literatura. El propósito de este trabajo es exponer en un documento las consideraciones a tener en cuenta cuando se implementa un convertidor push-pull alimentado en corriente. Estas consideraciones fueron clave para realizar un prototipo de 300 W energizado desde la red eléctrica y con 48 V de tensión en su salida.Palabras claves: convertidor, push-pull, construcción, alimentado en corriente.AbstractThis paper deals with the construction considerations for a current-fed push-pull converter. It is common to find sufficient bibliography about the operation principle of a current fed push-pull converter and the size of its elements. However, when building a prototype issues that were not considered and documented arise. The aim of this paper is to expose the considerations to consider when a current-fed push-pull converter is implemented. These considerations were the main insight to build a 300 W and 48 voltage output prototype, powered by the grid.Keywords: Push-Pull, converter, construction, current-fed