Using GWAS Data to Identify Copy Number Variants Contributing to Common Complex Diseases

Copy number variants (CNVs) account for more polymorphic base pairs in the human genome than do single nucleotide polymorphisms (SNPs). CNVs encompass genes as well as noncoding DNA, making these polymorphisms good candidates for functional variation. Consequently, most modern genome-wide association studies test CNVs along with SNPs, after inferring copy number status from the data generated by high-throughput genotyping platforms. Here we give an overview of CNV genomics in humans, highlighting patterns that inform methods for identifying CNVs. We describe how genotyping signals are used to identify CNVs and provide an overview of existing statistical models and methods used to infer location and carrier status from such data, especially the most commonly used methods exploring hybridization intensity. We compare the power of such methods with the alternative method of using tag SNPs to identify CNV carriers. As such methods are only powerful when applied to common CNVs, we describe two alternative approaches that can be informative for identifying rare CNVs contributing to disease risk. We focus particularly on methods identifying de novo CNVs and show that such methods can be more powerful than case-control designs. Finally we present some recommendations for identifying CNVs contributing to common complex disorders.Comment: Published in at http://dx.doi.org/10.1214/09-STS304 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Mechanics reveals the biological trigger in wrinkly fingers

The final publication is available at Springer via http://dx.doi.org/10.1007/s10439-016-1764-6Fingertips wrinkle due to long exposure to water. The biological reason for this morphological change is unclear and still not fully understood. There are two main hypotheses for the underlying mechanism of fingertip wrinkling: the ‘shrink’ model (in which the wrinkling is driven by the contraction of the lower layers of skin, associated with the shrinking of the underlying vasculature), and the ‘swell’ model (in which the wrinkling is driven by the swelling of the upper layers of the skin, associated with osmosis). In reality, contraction of the lower layers of the skin and swelling of the upper layers will happen simultaneously. However, the relative importance of these two mechanisms to drive fingertip wrinkling also remains unclear. Simulating the swelling in the upper layers of skin alone, which is associated with neurological disorders, we found that wrinkles appeared above an increase of volume of ˜10%.˜10%. Therefore, the upper layers can not exceed this swelling level in order to not contradict in vivo observations in patients with such neurological disorders. Simulating the contraction of the lower layers of the skin alone, we found that the volume have to decrease a ˜20%˜20% to observe wrinkles. Furthermore, we found that the combined effect of both mechanisms leads to pronounced wrinkles even at low levels of swelling and contraction when individually they do not. This latter results indicates that the collaborative effect of both hypothesis are needed to induce wrinkles in the fingertips. Our results demonstrate how models from continuum mechanics can be successfully applied to testing hypotheses for the mechanisms that underly fingertip wrinkling, and how these effects can be quantified.Peer ReviewedPostprint (published version

Polarons and Molecules in a Two-Dimensional Fermi Gas

We study an impurity atom in a two-dimensional Fermi gas using variational wave functions for (i) an impurity dressed by particle-hole excitations (polaron) and (ii) a dimer consisting of the impurity and a majority atom. In contrast to three dimensions, where similar calculations predict a sharp transition to a dimer state with increasing interspecies attraction, we show that the polaron ansatz always gives a lower energy. However, the exact solution for a heavy impurity reveals that both a two-body bound state and distortions of the Fermi sea are crucial. This reflects the importance of particle-hole pairs in lower dimensions and makes simple variational calculations unreliable. We show that the energy of an impurity gives important information about its dressing cloud, for which both ans\"atze give inaccurate results.Comment: 5 pages, 2 figures, minor change

Fatal lymphoproliferation and acute monocytic leukemia-like disease following infectious mononucleosis in the elderly

Three elderly patients are reported, in whom serologically confirmed recent infectious mononucleosis is followed by fatal lymphoproliferation (case 1), by acute monocytic leukemia (case 2), and by acute probably monocytic leukemia (case 3)

Feasibility of Inconspicuous GAN-generated Adversarial Patches against Object Detection

Standard approaches for adversarial patch generation lead to noisy conspicuous patterns, which are easily recognizable by humans. Recent research has proposed several approaches to generate naturalistic patches using generative adversarial networks (GANs), yet only a few of them were evaluated on the object detection use case. Moreover, the state of the art mostly focuses on suppressing a single large bounding box in input by overlapping it with the patch directly. Suppressing objects near the patch is a different, more complex task. In this work, we have evaluated the existing approaches to generate inconspicuous patches. We have adapted methods, originally developed for different computer vision tasks, to the object detection use case with YOLOv3 and the COCO dataset. We have evaluated two approaches to generate naturalistic patches: by incorporating patch generation into the GAN training process and by using the pretrained GAN. For both cases, we have assessed a trade-off between performance and naturalistic patch appearance. Our experiments have shown, that using a pre-trained GAN helps to gain realistic-looking patches while preserving the performance similar to conventional adversarial patches

A dipolar self-induced bosonic Josephson junction

We propose a new scheme for observing Josephson oscillations and macroscopic quantum self-trapping phenomena in a toroidally confined Bose-Einstein condensate: a dipolar self-induced Josephson junction. Polarizing the atoms perpendicularly to the trap symmetry axis, an effective ring-shaped, double-well potential is achieved which is induced by the dipolar interaction. By numerically solving the three-dimensional time-dependent Gross-Pitaevskii equation we show that coherent tunneling phenomena such as Josephson oscillations and quantum self-trapping can take place. The dynamics in the self-induced junction can be qualitatively described by a two-mode model taking into account both s-wave and dipolar interactions.Comment: Major changes. Accepted for publication in EP

Excitations of attractive 1-D bosons: Binding vs. fermionization

The stationary states of few bosons in a one-dimensional harmonic trap are investigated throughout the crossover from weak to strongly attractive interactions. For sufficient attraction, three different classes of states emerge: (i) N-body bound states, (ii) bound states of smaller fragments, and (iii) gas-like states that fermionize, that is, map to ideal fermions in the limit of infinite attraction. The two-body correlations and momentum spectra characteristic of the three classes are discussed, and the results are illustrated using the soluble two-particle model.Comment: 7 pages, 5 figure

Binding between two-component bosons in one dimension

We investigate the ground state of one-dimensional few-atom Bose-Bose mixtures under harmonic confinement throughout the crossover from weak to strong inter-species attraction. The calculations are based on the numerically exact multi-configurational time-dependent Hartree method. For repulsive components we detail the condition for the formation of a molecular Tonks-Girardeau gas in the regime of intermediate inter-species interactions, and the formation of a molecular condensate for stronger coupling. Beyond a critical inter-species attraction, the system collapses to an overall bound state. Different pathways emerge for unequal particle numbers and intra-species interactions. In particular, for mixtures with one attractive component, this species can be viewed as an effective potential dimple in the trap center for the other, repulsive component.Comment: 10 pages, 10 figure