DMET-Miner: Efficient discovery of association rules from pharmacogenomic data

AbstractMicroarray platforms enable the investigation of allelic variants that may be correlated to phenotypes. Among those, the Affymetrix DMET (Drug Metabolism Enzymes and Transporters) platform enables the simultaneous investigation of all the genes that are related to drug absorption, distribution, metabolism and excretion (ADME). Although recent studies demonstrated the effectiveness of the use of DMET data for studying drug response or toxicity in clinical studies, there is a lack of tools for the automatic analysis of DMET data. In a previous work we developed DMET-Analyzer, a methodology and a supporting platform able to automatize the statistical study of allelic variants, that has been validated in several clinical studies. Although DMET-Analyzer is able to correlate a single variant for each probe (related to a portion of a gene) through the use of the Fisher test, it is unable to discover multiple associations among allelic variants, due to its underlying statistic analysis strategy that focuses on a single variant for each time. To overcome those limitations, here we propose a new analysis methodology for DMET data based on Association Rules mining, and an efficient implementation of this methodology, named DMET-Miner. DMET-Miner extends the DMET-Analyzer tool with data mining capabilities and correlates the presence of a set of allelic variants with the conditions of patient’s samples by exploiting association rules. To face the high number of frequent itemsets generated when considering large clinical studies based on DMET data, DMET-Miner uses an efficient data structure and implements an optimized search strategy that reduces the search space and the execution time. Preliminary experiments on synthetic DMET datasets, show how DMET-Miner outperforms off-the-shelf data mining suites such as the FP-Growth algorithms available in Weka and RapidMiner. To demonstrate the biological relevance of the extracted association rules and the effectiveness of the proposed approach from a medical point of view, some preliminary studies on a real clinical dataset are currently under medical investigation

10th Workshop on Biomedical and Bioinformatics Challenges for Computer Science - BBC2017

Agapito, G., Cannataro, M., Castelli, M., Dondi, R., & Zoppis, I. (2017). 10th Workshop on Biomedical and Bioinformatics Challenges for Computer Science - BBC2017. Procedia Computer Science, 108, 1113-1114. https://doi.org/10.1016/j.procs.2017.05.279We present the 10th Workshop on Biomedical and Bioinformatics Challenges for Computer Science - BBC2017, held in Zurich, 12 - 14 June 2017.publishersversionpublishe

BioPAX-Parser: parsing and enrichment analysis of BioPAX pathways

Abstract Summary Biological pathways are fundamental for learning about healthy and disease states. Many existing formats support automatic software analysis of biological pathways, e.g. BioPAX (Biological Pathway Exchange). Although some algorithms are available as web application or stand-alone tools, no general graphical application for the parsing of BioPAX pathway data exists. Also, very few tools can perform pathway enrichment analysis (PEA) using pathway encoded in the BioPAX format. To fill this gap, we introduce BiP (BioPAX-Parser), an automatic and graphical software tool aimed at performing the parsing and accessing of BioPAX pathway data, along with PEA by using information coming from pathways encoded in BioPAX. Availability and implementation BiP is freely available for academic and non-profit organizations at https://gitlab.com/giuseppeagapito/bip under the LGPL 2.1, the GNU Lesser General Public License. Supplementary information Supplementary data are available at Bioinformatics online

Aging changes complexity of heart rate dynamics assessed by entropy and Lyapunov exponent analysis

In recent years, many research groups are trying to quantify the physiological signals of an individual, proposing new models to assess the complex dynamics of biological control systems. Indeed, life coincides with the good handling of the structures in the organism and of physiological control mechanisms, while disease and death coincide with the loss of structure and of coordinated functions. The homeodynamic systems which normally govern health are the same that cause pathological events when activated inadequately, or rather, when the balance between order and chaos of the elementary physiological processes is no longer effectively controlled in relation to any type of stress, both external and internal to the body. In a complex system, loss or alteration of communication between physiological signals means pathology. In this paper a signal analysis method based on Entropy (E), Lyapunov exponent (1), Median Absolute Deviation (MAD), Multiscale Entropy (MSE), is proposed to estimate the complexity of long-range temporal correlation heart rate (HR) time series for an elderly person and a young person both healthy. These new methods could improve overall understanding of the physiological system of the human organism, by adopting new models and experimental paradigms, such as those of fractality and entropy, who have the ability to direct from an organ medicine to a modern systemic medicine

The numerical simulation tool for the MAORY multiconjugate adaptive optics system

The Multiconjugate Adaptive Optics RelaY (MAORY) is and Adaptive Optics module to be mounted on the ESO European-Extremely Large Telescope (E-ELT). It is a hybrid Natural and Laser Guide System that will perform the correction of the atmospheric turbulence volume above the telescope feeding the Multi-AO Imaging Camera for Deep Observations Near Infrared spectro-imager (MICADO). We developed an end-to-end Monte- Carlo adaptive optics simulation tool to investigate the performance of a the MAORY and the calibration, acquisition, operation strategies. MAORY will implement Multiconjugate Adaptive Optics combining Laser Guide Stars (LGS) and Natural Guide Stars (NGS) measurements. The simulation tool implements the various aspect of the MAORY in an end to end fashion. The code has been developed using IDL and uses libraries in C++ and CUDA for efficiency improvements. Here we recall the code architecture, we describe the modeled instrument components and the control strategies implemented in the code.Comment: 6 pages, 1 figure, Proceeding 9909 310 of the conference SPIE Astronomical Telescopes + Instrumentation 2016, 26 June 1 July 2016 Edinburgh, Scotland, U

Petrología y geocronología K-Ar del complejo Marañón (Región Huánuco-Tingo María), Cordillera Oriental de los Andes Peruanos: consideraciones tectónicas preliminares

El Complejo Marañón incluye un conjunto de rocas metamórficas de grado bajo y de edad PreOrdoviciana, las que se encuentran expuestas de manera semi-continua a lo largo de la Cordillera Oriental Peruana, entre los ríos Marañón y Huallaga. Las relaciones de campo sugieren que se trata de una secuencia metamórfica, de bajo grado constituida por un intervalo de esquistos cuarzo-micáceos, intercalados con algunas meta-tufos y rocas carbonatadas, y otra de muy bajo grado constituida por pizarras y meta-arentias. Estructuralmente se observan 3 a 4 fábricas formadas en condiciones dúctiles en las rocas de más alto grado, y 2 en las de bajo grado. En la primera, la foliación principal está definida por las micas, y por Sn anterior siendo preservada en microlitones. Las otras fábricas son crenulaciones menores y plegamientos regionales sin recristalización metamórfica. Las rocas de más bajo grado presentan una estructura planar aparentemente subparalela con la estratificación, sobre la que se sobrepone un plegamiento asociado a un clivaje espaciado. Las características microestructurales de las rocas de bajo grado en la zona de Tingo-María, muestran el predominio de texturas elásticas relictas, y minerales detríticos (plagioclasas, feldespato-K, turmalina, muscovita). La deformación observada en meta-arenitas y rocas calcáreas, incluye calcitas con macias del tipo II y III, extinción ondulatoria, formación de subgranos, migración del borde de granos en el cuarzo y formación de sericita. En las pizarras son comunes residuos insolubles en zonas de crenulación y venas de cuarzo típicas de procesos de disolución por presión. Estos elementos indican temperaturas entre 200°-350° C (Ferrill, 1991, Burkhard, 1993, Passchier y Trouw, 1996, Ferril et al, in press)

Genetic variants associated with gastrointestinal symptoms in Fabry disease.

Gastrointestinal symptoms (GIS) are often among the earliest presenting events in Fabry disease (FD), an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A. Despite recent advances in clinical and molecular characterization of FD, the pathophysiology of the GIS is still poorly understood. To shed light either on differential clinical presentation or on intervariability of GIS in FD, we genotyped 1936 genetic markers across 231 genes that encode for drug-metabolizing enzymes and drug transport proteins in 49 FD patients, using the DMET Plus platform. All nine single nucleotide polymorphisms (SNPs) mapped within four genes showed statistically significant differences in genotype frequencies between FD patients who experienced GIS and patients without GIS: ABCB11 (odd ratio (OR) = 18.07, P = 0,0019; OR = 8.21, P = 0,0083; OR=8.21, P = 0,0083; OR = 8.21, P = 0,0083),SLCO1B1 (OR = 9.23, P = 0,0065; OR = 5.08, P = 0,0289; OR = 8.21, P = 0,0083), NR1I3 (OR = 5.40, P = 0,0191) and ABCC5 (OR = 14.44, P = 0,0060). This is the first study that investigates the relationships between genetic heterogeneity in drug absorption, distribution, metabolism and excretion (ADME) related genes and GIS in FD. Our findings provide a novel genetic variant framework which warrants further investigation for precision medicine in FD

U/Pb detrital zircon geochronology and Nd isotopes from Paleozoic metasedimentary rocks of the Marañon Complex: insights on the proto-Andean tectonic evolution of the Eastern Peruvian Andes

La evolución tectónica Proto-Andina de los Andes Peruanos se encuentra registrada en una serie discontinua de unidades metamórficas pre-Triásicas (Complejo Marañón), que se extienden entre los 6°-10° lat. S, a lo largo de la Cordillera Oriental. Con el fin de definir las características generales de su evolución tectónica y su proveniencia, fueron realizados análisis geocronológicos en rocas meta-sedimentarias, utilizando los métodos U/Pb LA-ICP-MS y SHRIMP en cristales de circones detríticos y metamórficos, así como análisis isotópico por el método Sm-Nd de muestras de roca total. Los resultados obtenidos en circones indican la existencia de tres unidades metamórficas formadas durante el Paleozoico Inferior, Medio y Superior. De otro lado, la existencia de circones detríticos con edades entre 1.0-3.0 Ga sugieren que el Craton Amazónico es una de las fuentes principales en la formación de los sedimentos, mientras que la presencia de edades Neoproterozoicas indica la existencia de un marco geodinámico más complejo para este segmento de la margen. Las edades modelo Sm-Nd TDM se encuentran entre 1.-2.1 Ga, y el ЄNd(T) calculado para el Paleozoico presenta valores negativos entre - 7 y -12, que conjuntamente sugieren una correlación con las provincias Rondoniano-San Ignacio y Sunsas del Craton Amazónico, así como la presencia de un retrabajamiento de corteza más antigua. Estas características geocronológicas indican que la Proto-margen Andina durante el Paleozoico registra una evolución orogénica caracterizada por eventos sucesivos de erosión, sedimentación y metamorfismo que retrabajan el material previamente formado

The Gray Needle: Large Grains in the HD 15115 Debris Disk from LBT/PISCES/Ks and LBTI/LMIRcam/L' Adaptive Optics Imaging

We present diffraction-limited \ks band and \lprime adaptive optics images of the edge-on debris disk around the nearby F2 star HD 15115, obtained with a single 8.4 m primary mirror at the Large Binocular Telescope. At \ks band the disk is detected at signal-to-noise per resolution element (SNRE) \about 3-8 from \about 1-2\fasec 5 (45-113 AU) on the western side, and from \about 1.2-2\fasec 1 (63-90 AU) on the east. At \lprime the disk is detected at SNRE \about 2.5 from \about 1-1\fasec 45 (45-90 AU) on both sides, implying more symmetric disk structure at 3.8 \microns . At both wavelengths the disk has a bow-like shape and is offset from the star to the north by a few AU. A surface brightness asymmetry exists between the two sides of the disk at \ks band, but not at \lprime . The surface brightness at \ks band declines inside 1\asec (\about 45 AU), which may be indicative of a gap in the disk near 1\asec. The \ks - \lprime disk color, after removal of the stellar color, is mostly grey for both sides of the disk. This suggests that scattered light is coming from large dust grains, with 3-10 \microns -sized grains on the east side and 1-10 \microns dust grains on the west. This may suggest that the west side is composed of smaller dust grains than the east side, which would support the interpretation that the disk is being dynamically affected by interactions with the local interstellar medium.Comment: Apj-accepted March 27 2012; minor correction

MAORY real-time computer preliminary design

MAORY is the Multi-conjugate Adaptive Optics module for the Extremely Large Telescope and it will be located on the Nasmyth platform of the telescope to feed scientific instruments. MAORY will re-image the telescope focal plane providing multi-conjugate adaptive optics correction of the wavefront distortion induced by the atmosphere. The system is based on six laser guide stars and three natural guide stars for sensing the wavefront distortion and three deformable mirrors for correcting it. We will show the current status of the preliminary design of the Real Time Computer in charge of carrying out all the calculations based on the measurements of the guide stars wavefront sensors. The hard real time (primary) loops are in charge of controlling the deformable mirrors and the lasers jitter compensation while the soft real- time (secondary) loops are in charge of updating the primary loops parameters as well as measuring or estimating the atmospheric parameters and the system performance. Telemetry data management/recording and calibration are the other tasks carried out by the real time computer