A statistical model for the identification of genes governing the incidence of cancer with age

The cancer incidence increases with age. This epidemiological pattern of cancer incidence can be attributed to molecular and cellular processes of individual subjects. Also, the incidence of cancer with ages can be controlled by genes. Here we present a dynamic statistical model for explaining the epidemiological pattern of cancer incidence based on individual genes that regulate cancer formation and progression. We incorporate the mathematical equations of age-specific cancer incidence into a framework for functional mapping aimed at identifying quantitative trait loci (QTLs) for dynamic changes of a complex trait. The mathematical parameters that specify differences in the curve of cancer incidence among QTL genotypes are estimated within the context of maximum likelihood. The model provides testable quantitative hypotheses about the initiation and duration of genetic expression for QTLs involved in cancer progression. Computer simulation was used to examine the statistical behavior of the model. The model can be used as a tool for explaining the epidemiological pattern of cancer incidence

Mechanism of glycan receptor recognition and specificity switch for avian, swine, and human adapted influenza virus hemagglutinins: a molecular dynamics perspective.

Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to prefer avian and human glycan receptor analogues with distinct topological profiles, pentasaccharides LSTa (alpha-2,3 linkage) and LSTc (alpha-2,6 linkage), in comparative molecular dynamics studies. On the basis of detailed analyses of the dynamic motions of the receptor binding domains (RBDs) and interaction energy profiles with individual glycan residues, we have identified approximately 30 residue positions in the RBD that present distinct profiles with the receptor analogues. Glycan binding constrained the conformational space sampling by the HA. Electrostatic steering appeared to play a key role in glycan binding specificity. The complex dynamic behaviors of the major SSE and trimeric interfaces with or without bound glycans suggested that networks of interactions might account for species specificity in these low affinity and high avidity (multivalent) interactions between different HA and glycans. Contact frequency, energetic decomposition, and H-bond analyses revealed species-specific differences in HA-glycan interaction profiles, not readily discernible from crystal structures alone. Interaction energy profiles indicated that mutation events at the set of residues such as 145, 156, 158, and 222 would favor human or avian receptor analogues, often through interactions with distal asialo-residues. These results correlate well with existing experimental evidence, and suggest new opportunities for simulation-based vaccine and drug development

Computing power of quantitative trait locus association mapping for haploid loci

<p>Abstract</p> <p>Background</p> <p>Statistical power calculations are a critical part of any study design for gene mapping. Most calculations assume that the locus of interest is biallelic. However, there are common situations in human genetics such as X-linked loci in males where the locus is haploid. The purpose of this work is to mathematically derive the biometric model for haploid loci, and to compute power for QTL mapping when the loci are haploid.</p> <p>Results</p> <p>We have derived the biometric model for power calculations for haploid loci and have developed software to perform these calculations. We have verified our calculations with independent mathematical methods.</p> <p>Conclusion</p> <p>Our results fill a need in power calculations for QTL mapping studies. Furthermore, failure to appropriately model haploid loci may cause underestimation of power.</p

Topological Homogeneity for Electron Microscopy Images

In this paper, the concept of homogeneity is defined, from a topological perspective, in order to analyze how uniform is the material composition in 2D electron microscopy images. Topological multiresolution parameters are taken into account to obtain better results than classical techniques.Ministerio de Economía y Competitividad MTM2016-81030-PMinisterio de Economía y Competitividad TEC2012-37868-C04-0

Searching (the) FIRST radio arcs near ACO clusters

Gravitational lensing (GL) of distant radio sources by galaxy clusters should produce radio arc(let)s. We extracted radio sources from the FIRST survey near Abell cluster cores and found their radio position angles to be uniformly distributed with respect to the cluster centres. This result holds even when we restrict the sample to the richest or most centrally condensed clusters, and to sources with high S/N and large axial ratio. Our failure to detect GL with statistical methods may be due to poor cluster centre positions. We did not find convincing candidates for arcs either. Our result agrees with theoretical estimates predicting that surveys much deeper than FIRST are required to detect the effect. This is in apparent conflict with the detection of such an effect claimed by Bagchi & Kapahi (1995).Comment: 6 pages; 8 figures and 1 style file are included; to appear in Proc. "Observational Cosmology with the New Radio Surveys", eds. M. Bremer, N. Jackson & I. Perez-Fournon, Kluwer Acad. Pres

Functional Mapping of Dynamic Traits with Robust t-Distribution

Functional mapping has been a powerful tool in mapping quantitative trait loci (QTL) underlying dynamic traits of agricultural or biomedical interest. In functional mapping, multivariate normality is often assumed for the underlying data distribution, partially due to the ease of parameter estimation. The normality assumption however could be easily violated in real applications due to various reasons such as heavy tails or extreme observations. Departure from normality has negative effect on testing power and inference for QTL identification. In this work, we relax the normality assumption and propose a robust multivariate -distribution mapping framework for QTL identification in functional mapping. Simulation studies show increased mapping power and precision with the distribution than that of a normal distribution. The utility of the method is demonstrated through a real data analysis

Speeding up Simplification of Polygonal Curves using Nested Approximations

We develop a multiresolution approach to the problem of polygonal curve approximation. We show theoretically and experimentally that, if the simplification algorithm A used between any two successive levels of resolution satisfies some conditions, the multiresolution algorithm MR will have a complexity lower than the complexity of A. In particular, we show that if A has a O(N2/K) complexity (the complexity of a reduced search dynamic solution approach), where N and K are respectively the initial and the final number of segments, the complexity of MR is in O(N).We experimentally compare the outcomes of MR with those of the optimal "full search" dynamic programming solution and of classical merge and split approaches. The experimental evaluations confirm the theoretical derivations and show that the proposed approach evaluated on 2D coastal maps either shows a lower complexity or provides polygonal approximations closer to the initial curves.Comment: 12 pages + figure

High Efficiency Differentiation of Human Pluripotent Stem Cells to Cardiomyocytes and Characterization by Flow Cytometry

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Automatically extracting functionally equivalent proteins from SwissProt

In summary, FOSTA provides an automated analysis of annotations in UniProtKB/Swiss-Prot to enable groups of proteins already annotated as functionally equivalent, to be extracted. Our results demonstrate that the vast majority of UniProtKB/Swiss-Prot functional annotations are of high quality, and that FOSTA can interpret annotations successfully. Where FOSTA is not successful, we are able to highlight inconsistencies in UniProtKB/Swiss-Prot annotation. Most of these would have presented equal difficulties for manual interpretation of annotations. We discuss limitations and possible future extensions to FOSTA, and recommend changes to the UniProtKB/Swiss-Prot format, which would facilitate text-mining of UniProtKB/Swiss-Prot