Discovering subgroups of patients from DNA copy number data using NMF on compacted matrices

In the study of complex genetic diseases, the identification of subgroups of patients sharing similar genetic characteristics represents a challenging task, for example, to improve treatment decision. One type of genetic lesion, frequently investigated in such disorders, is the change of the DNA copy number (CN) at specific genomic traits. Non-negative Matrix Factorization (NMF) is a standard technique to reduce the dimensionality of a data set and to cluster data samples, while keeping its most relevant information in meaningful components. Thus, it can be used to discover subgroups of patients from CN profiles. It is however computationally impractical for very high dimensional data, such as CN microarray data. Deciding the most suitable number of subgroups is also a challenging problem. The aim of this work is to derive a procedure to compact high dimensional data, in order to improve NMF applicability without compromising the quality of the clustering. This is particularly important for analyzing high-resolution microarray data. Many commonly used quality measures, as well as our own measures, are employed to decide the number of subgroups and to assess the quality of the results. Our measures are based on the idea of identifying robust subgroups, inspired by biologically/clinically relevance instead of simply aiming at well-separated clusters. We evaluate our procedure using four real independent data sets. In these data sets, our method was able to find accurate subgroups with individual molecular and clinical features and outperformed the standard NMF in terms of accuracy in the factorization fitness function. Hence, it can be useful for the discovery of subgroups of patients with similar CN profiles in the study of heterogeneous diseases.

Small area estimation for the price of habitation transaction: comparison of different uncertainty measures of temporal EBLUP

Local level planning requires statistics for small areas, but normally due to cost or logistic constraints, sample surveys are often planned to provide reliable estimates only for large geographical regions and large subgroups of a population.

Analysis of multiple change-points in normally distributed series.

Tesis (Maestría en Ciencias con Orientación en Matemáticas) UANL, 2013.

Localización de faltas en sistemas de distribución de energía eléctrica usando métodos basados en el modelo y métodos basados en el conocimiento

La calidad de energía eléctrica incluye la calidad del suministro y la calidad de la atención al cliente. La calidad del suministro a su vez se considera que la conforman dos partes, la forma de onda y la continuidad. En esta tesis se aborda la continuidad del suministro a través de la localización de faltas. Este problema se encuentra relativamente resuelto en los sistemas de transmisión, donde por las características homogéneas de la línea, la medición en ambos terminales y la disponibilidad de diversos equipos, se puede localizar el sitio de falta con una precisión relativamente alta. En sistemas de distribución, sin embargo, la localización de faltas es un problema complejo y aún no resuelto. La complejidad es debida principalmente a la presencia de conductores no homogéneos, cargas intermedias, derivaciones laterales y desbalances en el sistema y la carga. Además, normalmente, en estos sistemas sólo se cuenta con medidas en la subestación, y un modelo simplificado del circuito. Los principales esfuerzos en la localización han estado orientados al desarrollo de métodos que utilicen el fundamental de la tensión y de la corriente en la subestación, para estimar la reactancia hasta la falta. Como la obtención de la reactancia permite cuantificar la distancia al sitio de falta a partir del uso del modelo, el Método se considera Basado en el Modelo (MBM). Sin embargo, algunas de sus desventajas están asociadas a la necesidad de un buen modelo del sistema y a la posibilidad de localizar varios sitios donde puede haber ocurrido la falta, esto es, se puede presentar múltiple estimación del sitio de falta. Como aporte, en esta tesis se presenta un análisis y prueba comparativa entre varios de los MBM frecuentemente referenciados. Adicionalmente se complementa la solución con métodos que utilizan otro tipo de información, como la obtenida de las bases históricas de faltas con registros de tensión y corriente medidos en la subestación (no se limita solamente al fundamental). Como herramienta de extracción de información de estos registros, se utilizan y prueban dos técnicas de clasificación (LAMDA y SVM). Éstas relacionan las características obtenidas de la señal, con la zona bajo falta y se denominan en este documento como Métodos de Clasificación Basados en el Conocimiento (MCBC). La información que usan los MCBC se obtiene de los registros de tensión y de corriente medidos en la subestación de distribución, antes, durante y después de la falta. Los registros se procesan para obtener los siguientes descriptores: a) la magnitud de la variación de tensión ( dV ), b) la variación de la magnitud de corriente ( dI ), c) la variación de la potencia ( dS ), d) la reactancia de falta ( Xf ), e) la frecuencia del transitorio ( f ), y f) el valor propio máximo de la matriz de correlación de corrientes (Sv), cada uno de los cuales ha sido seleccionado por facilitar la localización de la falta. A partir de estos descriptores, se proponen diferentes conjuntos de entrenamiento y validación de los MCBC, y mediante una metodología que muestra la posibilidad de hallar relaciones entre estos conjuntos y las zonas en las cuales se presenta la falta, se seleccionan los de mejor comportamiento. Los resultados de aplicación, demuestran que con la combinación de los MCBC con los MBM, se puede reducir el problema de la múltiple estimación del sitio de falta. El MCBC determina la zona de falta, mientras que el MBM encuentra la distancia desde el punto de medida hasta la falta, la integración en un esquema híbrido toma las mejores características de cada método. En este documento, lo que se conoce como híbrido es la combinación de los MBM y los MCBC, de una forma complementaria. Finalmente y para comprobar los aportes de esta tesis, se propone y prueba un esquema de integración híbrida para localización de faltas en dos sistemas de distribución diferentes. Tanto los métodos que usan los parámetros del sistema y se fundamentan en la estimación de la impedancia (MBM), como aquellos que usan como información los descriptores y se fundamentan en técnicas de clasificación (MCBC), muestran su validez para resolver el problema de localización de faltas. Ambas metodologías propuestas tienen ventajas y desventajas, pero según la teoría de integración de métodos presentada, se alcanza una alta complementariedad, que permite la formulación de híbridos que mejoran los resultados, reduciendo o evitando el problema de la múltiple estimación de la falta.

Recall of deaf and normally hearing children on a short term memory task

This paper discusses memory and hearing impaired children.

A comparison of physical measurements of pure-tones, third-octave bands of noise and third-octave bands of speech to subjective judgments of audibility threshold, MCL and UCL for three normally hearing listeners

This study investigates the relation between physical measurements of pure-tones, third-octave bands of noise and third-octave bands of speech and subjective judgments of auditory threshold, most-comfortable listening level (MCL) and uncomfortable-listening level (UCL) for three normally hearing listeners.

Immediate recall by aphasic, deaf and normally hearing children for visual forms presented simultaneously or sequentially in tim

This paper discusses a study to investigate immediate recall of visual stimuli presented simultaneously or sequentially in time.

Phonological processing in the reading of deaf and normally hearing children

This paper reviews measurement of phonological processes in reading among deaf children and children who are of normal hearing.

The structural component of linguistic meaning and the reading of normally hearing and deaf children

This paper discusses an experiment in psycholinguistic method and its application to the field of education.

Gene expression profiling of human hibernating myocardium: Increased expression of B-type natriuretic peptide and proenkephalin in hypocontractile vs normally-contracting regions of the heart

A greater understanding of the molecular basis of hibernating myocardium may assist in identifying those patients who would most benefit from revascularization. Paired heart biopsies were taken from hypocontractile and normally-contracting myocardium (identified by cardiovascular magnetic resonance) from 6 patients with chronic stable angina scheduled for bypass grafting. Gene expression profiles of hypocontractile and normally-contracting samples were compared using Affymetrix microarrays. The data for patients with confirmed hibernating myocardium were analysed separately and a different, though overlapping, set (up to 380) of genes was identified which may constitute a molecular fingerprint for hibernating myocardium. The expression of B-type natriuretic peptide (BNP) was increased in hypocontractile relative to normally-contracting myocardium. The expression of BNP correlated most closely with the expression of proenkephalin and follistatin 3, which may constitute additional heart failure markers. Our data illustrate differential gene expression in hypocontractile and/hibernating myocardium relative to normally-contracting myocardium within individual human hearts. Changes in expression of these genes, including increased relative expression of natriuretic and other factors, may constitute a molecular signature for hypocontractile and/or hibernating myocardium.

Intake of total and subgroups of fat minimally affect the associations between selected single nucleotide polymorphisms in the PPARγ pathway and changes in anthropometry among European adults from cohorts of the DiOGenes study

BACKGROUND: Although the peroxisome proliferator-activated receptor γ (PPARγ) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association. OBJECTIVES: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARγ pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations. METHODS: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein β (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARγ gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y. RESULTS: The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele. Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat. CONCLUSIONS: Among European men and women, the influence of dietary fat on associations between SNPs in the PPARγ pathway and anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation.

The three-dimensional structure of bothropasin, the main hemorrhagic factor from Bothrops jararaca venom: Insights for a new classification of snake venom metalloprotease subgroups

Bothropasin is a 48 kDa hemorrhagic PIII snake venom metalloprotease (SVMP) isolated from Bothrops jararaca, containing disintegrin/cysteine-rich adhesive domains. Here we present the crystal structure of bothropasin complexed with the inhibitor POL647. The catalytic domain consists of a scaffold of two subdomains organized similarly to those described for other SVMPs, including the zinc and calcium-binding sites. The free cysteine residue Cys(189) is located within a hydrophobic core and it is not available for disulfide bonding or other interactions. There is no identifiable secondary structure for the disintegrin domain, but instead it is composed mostly of loops stabilized by seven disulfide bonds and by two calcium ions. The ECD region is in a loop and is structurally related to the RGD region of RGD disintegrins, which are derived from I`ll SVMPs. The ECD motif is stabilized by the Cys(117)_Cys(310) disulfide bond (between the disintegrin and cysteine-rich domains) and by one calcium ion. The side chain of Glu(276) of the ECD motif is exposed to solvent and free to make interactions. In bothropasin, the HVR (hyper-variable region) described for other Pill SVMPs in the cysteine-rich domain, presents a well-conserved sequence with respect to several other Pill members from different species. We propose that this subset be referred to as PIII-HCR (highly conserved region) SVMPs. The differences in the disintegrin-like, cysteine-rich or disintegrin-like cysteine-rich domains may be involved in selecting target binding, which in turn could generate substrate diversity or specificity for the catalytic domain. (C) 2008 Elsevier Ltd. All rights reserved.

Generalizations of Pelczynski`s decomposition method for Banach spaces containing a complemented copy of their squares

Suppose that X and Y are Banach spaces isomorphic to complemented subspaces of each other. In 1996, W. T. Gowers solved the Schroeder- Bernstein Problem for Banach spaces by showing that X is not necessarily isomorphic to Y. However, if X-2 is complemented in X with supplement A and Y-2 is complemented in Y with supplement B, that is, { X similar to X-2 circle plus A Y similar to Y-2 circle plus B, then the classical Pelczynski`s decomposition method for Banach spaces shows that X is isomorphic to Y whenever we can assume that A = B = {0}. But unfortunately, this is not always possible. In this paper, we show that it is possible to find all finite relations of isomorphism between A and B which guarantee that X is isomorphic to Y. In order to do this, we say that a quadruple (p, q, r, s) in N is a P-Quadruple for Banach spaces if X is isomorphic to Y whenever the supplements A and B satisfy A(p) circle plus B-q similar to A(r) circle plus B-s . Then we prove that (p, q, r, s) is a P-Quadruple for Banach spaces if and only if p - r = s - q = +/- 1.