KinMutRF: a random forest classifier of sequence variants in the human protein kinase superfamily

Background: The association between aberrant signal processing by protein kinases and human diseases such as cancer was established long time ago. However, understanding the link between sequence variants in the protein kinase superfamily and the mechanistic complex traits at the molecular level remains challenging: cells tolerate most genomic alterations and only a minor fraction disrupt molecular function sufficiently and drive disease. Results: KinMutRF is a novel random-forest method to automatically identify pathogenic variants in human kinases. Twenty six decision trees implemented as a random forest ponder a battery of features that characterize the variants: a) at the gene level, including membership to a Kinbase group and Gene Ontology terms; b) at the PFAM domain level; and c) at the residue level, the types of amino acids involved, changes in biochemical properties, functional annotations from UniProt, Phospho.ELM and FireDB. KinMutRF identifies disease-associated variants satisfactorily (Acc: 0.88, Prec:0.82, Rec:0.75, F-score:0.78, MCC:0.68) when trained and cross-validated with the 3689 human kinase variants from UniProt that have been annotated as neutral or pathogenic. All unclassified variants were excluded from the training set. Furthermore, KinMutRF is discussed with respect to two independent kinase-specific sets of mutations no included in the training and testing, Kin-Driver (643 variants) and Pon-BTK (1495 variants). Moreover, we provide predictions for the 848 protein kinase variants in UniProt that remained unclassified. A public implementation of KinMutRF, including documentation and examples, is available online (http://kinmut2.bioinfo.cnio.es). The source code for local installation is released under a GPL version 3 license, and can be downloaded from https://github.com/Rbbt-Workflows/KinMut2. Conclusions: KinMutRF is capable of classifying kinase variation with good performance. Predictions by KinMutRF compare favorably in a benchmark with other state-of-the-art methods (i.e. SIFT, Polyphen-2, MutationAssesor, MutationTaster, LRT, CADD, FATHMM, and VEST). Kinase-specific features rank as the most elucidatory in terms of information gain and are likely the improvement in prediction performance. This advocates for the development of family-specific classifiers able to exploit the discriminatory power of features unique to individual protein families

Influence of tillage on soil surface roughness structure andsurface porosity.

Soil erosion is a complex phenomenon involving the detachment and transport of soil particles, storage and runoff of rainwater, and infiltration. The relative magnitude and importance of these processes depends on several factors being one of them surface microtopography, usually quantified trough soil surface roughness (SSR). Surface soil porosity and SSR can be altered by tillage operation. Even though the surface porosity is an important parameter of a tilled field, however, no practical technique for rapid and non-contact measurement of surface porosity has been developed yet

Biometría ecográfica del globo ocular en caballos (Equus ferus caballus) de trabajo del departamento de Córdoba, Colombia

The B-mode ultrasound technique offers the possibility of performing an ocular biometric evaluation of the horse. In Colombia there are no reports on ocular biometric measurements in horses, so the objective of this article was to report the ultrasound appearance of the normal eye and obtain biometric values that can serve as a basis for ocular evaluation. A descriptive study was conducted in the eyes of 50 working horses from the department of Córdoba. The anterior chamber (AC), lens length (Ll), lens width (Lw), vitreous chamber (VC) and axial globe length (AGL) were measured by ultrasound. The sample consisted mainly of Colombian Creole horses (60%) and Appaloosa (32%), 58% were males, average age of 6.7±4.9 years. The biometric values obtained corresponded to AC: 0.68±0.08 cm; Ll: 1.11±0.09 cm, Lw: 2.00±0.16 cm; VC: 1.80±0.15 cm, and AGL: 3.91±0.28 cm. Sex differences were observed for Lw and AGL.La técnica de ultrasonido en modo B ofrece la posibilidad de realizar una evaluación biométrica ocular del caballo. En Colombia no se encuentran reportes sobre mediciones biométricas oculares en caballos, por lo que el objetivo de este artículo fue reportar la apariencia ecográfica del ojo normal y obtener valores biométricos que puedan servir de base para la evaluación ocular. Se realizó un estudio descriptivo en los ojos de 50 caballos de trabajo del departamento de Córdoba, Colombia. Se midió mediante ecografía la cámara anterior (CA), largo del lente (Ll), ancho del lente (La), cámara vítrea (CV) y longitud axial del globo (LAG). La muestra estuvo constituida principalmente por caballos de raza criollo colombiano (60%) y Appaloosa (32%), 58% fueron machos, edad promedio de 6.7±4.9 años. Los valores biométricos obtenidos correspondieron a CA: 0.68±0.08 cm; Ll: 1.11±0.09 cm, La: 2.00±0.16 cm; CV: 1.80±0.15 cm, y LAG: 3.91±0.28 cm. Se observó diferencia entre sexos para La y LAG

A two-stage approach for the spatio-temporal analysis of high-throughput phenotyping data

High throughput phenotyping (HTP) platforms and devices are increasingly used for the characterization of growth and developmental processes for large sets of plant genotypes. Such HTP data require challenging statistical analyses in which longitudinal genetic signals need to be estimated against a background of spatio-temporal noise processes. We propose a two-stage approach for the analysis of such longitudinal HTP data. In a first stage, we correct for design features and spatial trends per time point. In a second stage, we focus on the longitudinal modelling of the spatially corrected data, thereby taking advantage of shared longitudinal features between genotypes and plants within genotypes. We propose a flexible hierarchical three-level P-spline growth curve model, with plants/plots nested in genotypes, and genotypes nested in populations. For selection of genotypes in a plant breeding context, we show how to extract new phenotypes, like growth rates, from the estimated genotypic growth curves and their first-order derivatives. We illustrate our approach on HTP data from the PhenoArch greenhouse platform at INRAE Montpellier and the outdoor Field Phenotyping platform at ETH Zürich.Ministerio de Ciencia, Innovación y Universidades | Ref. BCAM Severo Ochoa accreditation SEV-2017-0718Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung | Ref. project PhenoCOOL (project no. 169542)Horizon 2020 Framework Programme | Ref. grant agreement ID 731013 (EPPN2020)Ministerio de Ciencia, Innovación y Universidades | Ref. MTM2017-82379-

Iron bioaccessibility and sensory analysis of extruded cereals fortified with different Fe sources

To increase iron (Fe) intake in Fe deficiency-risk groups the combination of Fe source and food-vehicle must be chosen in order to minimize inhibitory effects of food matrix. Fe dialyzability and sensory properties were tested in six model systems (MS) made with extruded cereals fortified with different Fe sources such as FeNaEDTA, FeSO4 and EDTA/FeSO4 among others and with or without the addition of milk. Proximate composition and phytate content were also evaluated. Results showed that Fe dialyzability from samples fortified with FeNaEDTA was less affected by the presence of inhibitory factors such as phytates and milk. The addition of FeSO4 to the extrudates showed sensory differences. Furthermore, fortification with EDTA/FeSO4 or FeNaEDTA showed no sensory differences compared with unfortified or Feº (elemental iron) fortified matrix, with the advantage of increased iron bioaccessibility.Fil: Cagnasso, Carolina Elisa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Calviño, Amalia Mirta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lopez, Laura Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cellerino, Karina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dyner, Luis Marcelo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Binaghi, Maria Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rodriguez, Viviana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Drago, Silvina Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Tecnología de los Alimentos; ArgentinaFil: Gonzalez, Rolando Jose. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Tecnología de los Alimentos; ArgentinaFil: Valencia, Mirta Eva. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

PLANEACIÓN DIDÁCTICA GENERAL DE LA ASIGNATURA: CÁLCULO DIFERENCIAL 2017-B

GUÍA DIDÁCTICA / PLANEACIÓN DIDÁCTICA (NMS

PLANEACIÓN DIDÁCTICA GENERAL DE LA ASIGNATURA: ARITMÉTICA Y LENGUAJE MATEMÁTICO 2017B

GUÍA DIDÁCTICA / PLANEACIÓN DIDÁCTICA (NMS

PLANEACIÓN DIDÁCTICA GENERAL DE LA ASIGNATURA: TRIGONOMETRÍA 2017- B

GUÍA DIDÁCTICA / PLANEACIÓN DIDÁCTICA (NMS

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

Mitochondrial genome sequencing of marine leukaemias reveals cancer contagion between clam species in the Seas of Southern Europe

20 Pág.Clonally transmissible cancers are tumour lineages that are transmitted between individuals via the transfer of living cancer cells. In marine bivalves, leukaemia-like transmissible cancers, called hemic neoplasia (HN), have demonstrated the ability to infect individuals from different species. We performed whole-genome sequencing in eight warty venus clams that were diagnosed with HN, from two sampling points located more than 1000 nautical miles away in the Atlantic Ocean and the Mediterranean Sea Coasts of Spain. Mitochondrial genome sequencing analysis from neoplastic animals revealed the coexistence of haplotypes from two different clam species. Phylogenies estimated from mitochondrial and nuclear markers confirmed this leukaemia originated in striped venus clams and later transmitted to clams of the species warty venus, in which it survives as a contagious cancer. The analysis of mitochondrial and nuclear gene sequences supports all studied tumours belong to a single neoplastic lineage that spreads in the Seas of Southern Europe.We thank the Galicia Supercomputing Centre (CESGA) for the availability of informatic resources. JMCT, SR, SD, and JT are supported by European Research Council (ERC) Starting Grant 716,290 SCUBA CANCERS. ALB is supported by MINECO PhD fellowship BES-2016-078166. DG-S is supported by postdoctoral contract ED481B/2018/091 from Xunta de Galicia. DP is supported by ERC grant ERC-617457-PHYLOCANCER and by Spanish Ministry of Economy and Competitiveness (MINECO) grant PID2019-106247GB-I00. This research was partially funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement 730984, ASSEMBLE Plus project. CESAM got financial support from FCT/MEC (UIDP/50017/2020, UIDB/50017/2020).Peer reviewe