RUbioSeq+: A multiplatform application that executes parallelized pipelines to analyse next-generation sequencing data

This is the peer reviewed version of the following article: Computer Methods and Programs in Biomedine 138 (2016): 73-81, which has been published in final form at http://dx.doi.org/10.1016/j.cmpb.2016.10.008Background and objective To facilitate routine analysis and to improve the reproducibility of the results, next-generation sequencing (NGS) analysis requires intuitive, efficient and integrated data processing pipelines. Methods We have selected well-established software to construct a suite of automated and parallelized workflows to analyse NGS data for DNA-seq (single-nucleotide variants (SNVs) and indels), CNA-seq, bisulfite-seq and ChIP-seq experiments. Results Here, we present RUbioSeq+, an updated and extended version of RUbioSeq, a multiplatform application that incorporates a suite of automated and parallelized workflows to analyse NGS data. This new version includes: (i) an interactive graphical user interface (GUI) that facilitates its use by both biomedical researchers and bioinformaticians, (ii) a new pipeline for ChIP-seq experiments, (iii) pair-wise comparisons (case–control analyses) for DNA-seq experiments, (iv) and improvements in the parallelized and multithreaded execution options. Results generated by our software have been experimentally validated and accepted for publication. Conclusions RUbioSeq+ is free and open to all users at http://rubioseq.bioinfo.cnio.es/.M.R-C is funded by the BLUEPRINT Consortium (FP7/ 2007-2013) under grant agreement number 282510. J.M.F is funded by the INB Node 2 - CNIO, a member of Proteored - PRB2-ISCIII and is supported by grant PT13/0001, of the PE I+D+i 2013-2016, funded by ISCIII and FEDER. H.L-F is funded by a postdoctoral fellowship from the Xunta de Galicia. F.F-R and D.G-P are funded by the European Union's Seventh Framework Programme FP7/REGPOT 2012 2013.1 under grant agreement n° 316265 (BIOCAPS) and the "Platform of integration of intelligent techniques for analysis of biomedical information" project (TIN2013-47153-C3-3-R) financed by the Spanish Ministry of Economy and Competitiveness C.FT is funded by the "Spanish National Youth Guarantee Implementation Plan” (2013/2016) financed by the Spanish Ministry of Economy and Competitivenes

La planimetría como forma de conocimiento en las Iglesias de Guadalajara

Durante los dos últimos años, el grupo de investigación AIPA “Análisis e Intervención en el Patrimonio Arquitectónico de la Universidad Politécnica de Madrid2, ha venido estudiando algunas iglesias de la provincia de Guadalajara, que presentaban problemas en su conservación. En ellas se han podido observar elementos comunes; tipológicos, morfológicos, en sus sistemas constructivos y en su evolución, que podría repercutir en la aparición y desarrollo de determinados daños, habituales en muchas de estas iglesias. La realización de levantamientos planimétricos de los edificios ha sido vital y nos ha permitido valorar la evolución de sus fábricas a lo largo del tiempo. A continuación presentamos cuatro casos significativos sobre esta experiencia y que son el objeto de la comunicación

Reconstrucción ideal de un artesonado de la iglesia de Sta. Mª de la Cuesta de Durón a partir de los elementos encontrados durante su restauración

El lamentable estado del templo hizo que Luis de Villanueva y Susana Mora redactaran un Proyecto de Restauración, cuya primera fase era la Restauración de cubiertas. Éstas se desmontaron cuidadosamente, apareciendo en la nave sur una viga cambiada de posición de labra supuestamente mudéjar, lo que hizo exagerar las precauciones. Pudimos así observar otra ménsula de madera labrada que servía de apoyo a elementos pétreos de la cabecera. En la nave lateral norte se encontraron durmientes, varios tirantes, y rebajes equidistantes, que podrían corresponder a estribos. En la nave central, formando parte de las quijeras, estaban integrados elementos con sencillas decoraciones azuladas, que podrían corresponder a restos de los citados estribos de la nave lateral. Las hipótesis se comprobaron, y con el apoyo de textos especializados, se formuló una propuesta de techumbre que podría acercarnos a las construcciones de esta zona del Señorío de Mendoza entre los siglos XV y XVI

Analysis of Paired Primary-Metastatic Hormone-Receptor Positive Breast Tumors (HRPBC) Uncovers Potential Novel Drivers of Hormonal Resistance

We sought to identify genetic variants associated with disease relapse and failure to hormonal treatment in hormone-receptor positive breast cancer (HRPBC). We analyzed a series of HRPBC with distant relapse, by sequencing pairs (n = 11) of tumors (primary and metastases) at >800X. Comparative genomic hybridization was performed as well. Top hits, based on the frequency of alteration and severity of the changes, were tested in the TCGA series. Genes determining the most parsimonious prognostic signature were studied for their functional role in vitro, by performing cell growth assays in hormonal-deprivation conditions, a setting that mimics treatment with aromatase inhibitors. Severe alterations were recurrently found in 18 genes in the pairs. However, only MYC, DNAH5, CSFR1, EPHA7, ARID1B, and KMT2C preserved an independent prognosis impact and/or showed a significantly different incidence of alterations between relapsed and non-relapsed cases in the TCGA series. The signature composed of MYC, KMT2C, and EPHA7 best discriminated the clinical course, (overall survival 90,7 vs. 144,5 months; p = 0.0001). Having an alteration in any of the genes of the signature implied a hazard ratio of death of 3.25 (p<0.0001), and early relapse during the adjuvant hormonal treatment. The presence of the D348N mutation in KMT2C and/or the T666I mutation in the kinase domain of EPHA7 conferred hormonal resistance in vitro. Novel inactivating mutations in KMT2C and EPHA7, which confer hormonal resistance, are linked to adverse clinical course in HRPBC

Antecedentes y perspectivas de algunas enfermedades prioritarias que afectan a la ganadería bovina en México

The review focused on concisely presenting the contributions that INIFAP researchers have developed, directly or in collaboration with researchers from other institutions, on different aspects of the diseases that affect cattle farming in Mexico. It describes the research on viral diseases such as rabies and bovine viral diarrhea; bacterial diseases such as anaplasmosis, brucellosis, tuberculosis, paratuberculosis, leptospirosis and bovine respiratory disease, and among parasitic diseases, tick infestation and babesiosis. It identifies potential lines of research that can help mitigate the impact of diseases on production. It considers contributions on the development or adaptation of serological and molecular diagnostic techniques and the diagnosis of resistance to ixodicides. In addition, it indicates epidemiological parameters of the diseases and makes reference to the biologics generated, which include vaccines against rabies, anaplasmosis and babesiosis; bacterin against leptospirosis, and a bacterin-toxoid against pneumonia. It also discusses the evaluations of the use of BCG against tuberculosis and a new generation vaccine against brucellosis. The review concludes that the research of INIFAP in animal health must necessarily have the omic sciences as a perspective. This is the only way to complement the understanding of disease mechanisms, the development of new diagnostic techniques and the design of effective and safe vaccines. Therefore, the great challenge will be the involvement of the animal health area in the concept of "One Health".La revisión se enfocó en presentar de manera concisa las aportaciones que investigadores del INIFAP, han desarrollado directamente o en colaboración con investigadores de otras instituciones sobre diferentes aspectos de las enfermedades que afectan a la ganadería bovina en México. Se describen investigaciones sobre enfermedades virales como la rabia y la diarrea viral bovina; bacterianas como la anaplasmosis, brucelosis, tuberculosis, paratuberculosis, leptospirosis y enfermedad respiratoria bovina; de las enfermedades parasitarias se incluye a la infestación por garrapatas y a la babesiosis. Se identifican posibles líneas de investigación que pueden coadyuvar a mitigar el impacto de las enfermedades en la producción. Se señalan aportes sobre el desarrollo o adaptación de técnicas diagnósticas de tipo serológico y molecular y se considera el diagnóstico de resistencia a los ixodicidas. Además, se indican parámetros epidemiológicos de las enfermedades y se refieren los biológicos generados que comprenden vacuna contra rabia, anaplasmosis y babesiosis; bacterina contra leptospirosis y una bacterina-toxoide contra neumonías. Asimismo, se comentan las evaluaciones del uso de BCG contra tuberculosis y una vacuna de nueva generación contra la brucelosis. En la revisión se concluye que la investigación del INIFAP en salud animal debe forzosamente tener como perspectiva las ciencias ómicas. Solo así se complementará el entendimiento de los mecanismos de las enfermedades, el desarrollo de nuevas técnicas diagnósticas y el diseño de vacunas efectivas y seguras. De modo que el gran reto será el involucramiento del área de salud animal al concepto de "Una Salud"

Extreme genomic erosion after recurrent demographic bottlenecks in the highly endangered Iberian lynx

Background: Genomic studies of endangered species provide insights into their evolution and demographic history, reveal patterns of genomic erosion that might limit their viability, and offer tools for their effective conservation. The Iberian lynx (Lynx pardinus) is the most endangered felid and a unique example of a species on the brink of extinction. Results: We generate the first annotated draft of the Iberian lynx genome and carry out genome-based analyses of lynx demography, evolution, and population genetics. We identify a series of severe population bottlenecks in the history of the Iberian lynx that predate its known demographic decline during the 20th century and have greatly impacted its genome evolution. We observe drastically reduced rates of weak-to-strong substitutions associated with GC-biased gene conversion and increased rates of fixation of transposable elements. We also find multiple signatures of genetic erosion in the two remnant Iberian lynx populations, including a high frequency of potentially deleterious variants and substitutions, as well as the lowest genome-wide genetic diversity reported so far in any species. Conclusions: The genomic features observed in the Iberian lynx genome may hamper short- and long-term viability through reduced fitness and adaptive potential. The knowledge and resources developed in this study will boost the research on felid evolution and conservation genomics and will benefit the ongoing conservation and management of this emblematic species

Molecular basis of targeted therapy in T/NKcell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed

Comparación de secuencias genómicas e identificación de proteínas utilizando FPGAS

La comparación de cadenas es una parte importante de muchos programas y aplicaciones, en particular, es creciente su uso en el terreno de la biología y la investigación científica. Miles de secuencias provenientes de enormes bases de datos de contenido genético son diariamente comparadas con este motivo. Por ello, se hace necesaria la utilización de algoritmos rápidos, y no sólo eso, sino que sus resultados sean lo más fiables posible. Los algoritmos existentes actualmente se basan en la búsqueda exacta, es decir, en comprobar si una cadena es igual a otra dada, o en la búsqueda inexacta, consistente en hallar un coste o valoración que indicaría lo que una cadena difiere de otra. El algoritmo de Smith-Waterman pertenece a este segundo grupo y es el que hemos elegido para implementar la comparación entre secuencias de ADN, dado que es el mejor dentro de los algoritmos de búsqueda inexacta. Utilizando Smith-Waterman quedaría resuelto el problema de la fiabilidad, pero también es muy importante la velocidad, ya que cuanto más rápido se obtenga el resultado, el trabajo de los investigadores o programas también se acelerará y por lo tanto mejorará. Una solución software del algoritmo se obtendría aproximadamente en un tiempo N *M, siendo N y M las longitudes de las cadenas a comparar. Mientras que una solución hardware aprovechando el paralelismo que aportan arquitecturas como los arrays sistólicos podría obtenerla en N + M. Con lo cual, si las cadenas son largas, como es el caso de las secuencias de ADN, la mejora es enormemente visible. Por ello, para implementar el sistema hemos elegido la opción hardware y para hacerlo utilizaremos FPGA’s. [ABSTRACT] String comparison is an important part of many programs and applications. Its use is especially growing in biology and scientific research. For this reason, thousands of sequences coming from enormous data bases with genetic contents, are compared daily. Therefore fast algorithms with reliable results are necessary. The currently existent algorithms are based either on exact or on inexact search. Exact search verifies if a string is equal to another given one, and inexact search consists in finding a cost or valuation which indicates the resemblance between two strings. The Smith-Waterman algorithm is based on inexact search and is the one we have chosen to implement the comparison of DNA strings given it is the best choice for inexact search. By using Smith-Waterman the reliability problem is solved, but the speed is also very important due to the fact that the faster the result is obtained, the faster the work of researchers and programs is done and therefore improves. A software solution of the algorithm could be obtained in approximately N*M, where N and M are the lengths of the strings to compare. Meanwhile, a hardware solution could be obtained in N+M, taking advantage of the paralelism architectures, such as systolic arrays, offer. Therefore the improvement on large strings, for instance DNA sequences, is clearly visible. Because of this, to implement the system we have chosen the hardware approach using FPGA’s