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genome scale model

Marjolein M J van Donkelaar, Martine Hoogman, Irene Pappa, Henning Tiemeier, Jan K Buitelaar, Barbara Franke, Janita Bralten
Reactive and proactive subtypes of aggression have been recognized to help parse etiological heterogeneity of this complex phenotype. With a heritability of about 50%, genetic factors play a role in the development of aggressive behavior. Imaging studies implicate brain structures related to social behavior in aggression etiology, most notably the amygdala and striatum. This study aimed to gain more insight into the pathways from genetic risk factors for aggression to aggression phenotypes. To this end, we conducted genome-wide gene-based cross-trait meta-analyses of aggression with the volumes of amygdala, nucleus accumbens and caudate nucleus to identify genes influencing both aggression and aggression-related brain volumes...
2018: Frontiers in Behavioral Neuroscience
Chisato Shimanoe, Tsuyoshi Hachiya, Megumi Hara, Yuichiro Nishida, Keitaro Tanaka, Yoichi Sutoh, Atsushi Shimizu, Asahi Hishida, Sayo Kawai, Rieko Okada, Takashi Tamura, Keitaro Matsuo, Hidemi Ito, Etsuko Ozaki, Daisuke Matsui, Rie Ibusuki, Ippei Shimoshikiryo, Naoyuki Takashima, Aya Kadota, Kokichi Arisawa, Hirokazu Uemura, Sadao Suzuki, Miki Watanabe, Kiyonori Kuriki, Kaori Endoh, Haruo Mikami, Yohko Nakamura, Yukihide Momozawa, Michiaki Kubo, Masahiro Nakatochi, Mariko Naito, Kenji Wakai
Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 13,088 participants aged 35-69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were measured and analyzed...
April 17, 2018: Genes, Brain, and Behavior
Juan Francisco Viso, Patricia Belelli, Matías Machado, Humberto González, Sergio Pantano, María Julia Amundarain, Fernando Zamarreño, Maria Marta Branda, Diego M A Guérin, Marcelo D Costabel
In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in the capsid of small and non-enveloped icosahedral viruses. With this purpose we examine Triatoma Virus (TrV) as a case study. This virus has a stable capsid under highly acidic conditions but disassembles and releases the genome in alkaline environments. Our calculations range from a subtle sub-atomic proton interchange to the dismantling of a large-scale system representing several million of atoms. Our results provide structure-based explanations for the three roles played by the capsid to enable genome release...
April 16, 2018: PLoS Computational Biology
Busra Aydin, Tugba Ozer, Ebru Toksoy Oner, Kazim Yalcin Arga
Metabolic systems engineering is being used to redirect microbial metabolism for the overproduction of chemicals of interest with the aim of transforming microbial hosts into cellular factories. In this study, a genome-based metabolic systems engineering approach was designed and performed to improve biopolymer biosynthesis capability of a moderately halophilic bacterium Halomonas smyrnensis AAD6T producing levan, which is a fructose homopolymer with many potential uses in various industries and medicine. For this purpose, the genome-scale metabolic model for AAD6T was used to characterize the metabolic resource allocation, specifically to design metabolic engineering strategies for engineered bacteria with enhanced levan production capability...
March 2018: Omics: a Journal of Integrative Biology
Amalio Telenti, Christoph Lippert, Pi-Chuan Chang, Mark DePristo
The human genome is now investigated through high throughput functional assays, and through the generation of population genomic data. These advances support the identification of functional genetic variants and the prediction of traits (eg. deleterious variants and disease). This review summarizes lessons learned from the large-scale analyses of genome and exome datasets, modeling of population data and machine learning strategies to solve complex genomic sequence regions. The review also portrays the rapid adoption of artificial intelligence/deep neural networks in genomics; in particular, deep learning approaches are well suited to model the complex dependencies in the regulatory landscape of the genome, and to provide predictors for genetic variant calling and interpretation...
April 10, 2018: Human Molecular Genetics
Jackson Peter, Matteo De Chiara, Anne Friedrich, Jia-Xing Yue, David Pflieger, Anders Bergström, Anastasie Sigwalt, Benjamin Barre, Kelle Freel, Agnès Llored, Corinne Cruaud, Karine Labadie, Jean-Marc Aury, Benjamin Istace, Kevin Lebrigand, Pascal Barbry, Stefan Engelen, Arnaud Lemainque, Patrick Wincker, Gianni Liti, Joseph Schacherer
Large-scale population genomic surveys are essential to explore the phenotypic diversity of natural populations. Here we report the whole-genome sequencing and phenotyping of 1,011 Saccharomyces cerevisiae isolates, which together provide an accurate evolutionary picture of the genomic variants that shape the species-wide phenotypic landscape of this yeast. Genomic analyses support a single 'out-of-China' origin for this species, followed by several independent domestication events. Although domesticated isolates exhibit high variation in ploidy, aneuploidy and genome content, genome evolution in wild isolates is mainly driven by the accumulation of single nucleotide polymorphisms...
April 11, 2018: Nature
Steve D M Brown, Chris C Holmes, Ann-Marie Mallon, Terrence F Meehan, Damian Smedley, Sara Wells
We are entering a new era of mouse phenomics, driven by large-scale and economical generation of mouse mutants coupled with increasingly sophisticated and comprehensive phenotyping. These studies are generating large, multidimensional gene-phenotype data sets, which are shedding new light on the mammalian genome landscape and revealing many hitherto unknown features of mammalian gene function. Moreover, these phenome resources provide a wealth of disease models and can be integrated with human genomics data as a powerful approach for the interpretation of human genetic variation and its relationship to disease...
April 6, 2018: Nature Reviews. Genetics
Yi Tan, Tommy Tsan-Yuk Lam, Lea A Heberlein-Larson, Sandra C Smole, Albert J Auguste, Scott Hennigan, Rebecca A Halpin, Nadia Fedorova, Vinita Puri, Timothy B Stockwell, Meghan H Shilts, Theodore Andreadis, Philip M Armstrong, Robert B Tesh, Scott C Weaver, Thomas R Unnasch, Alexander T Ciota, Laura D Kramer, Suman R Das
Eastern equine encephalitis virus (EEEV) has a high case-fatality rate in horses and humans, and Florida has been hypothesized to be the source of EEEV epidemics for the northeastern U.S. To test this hypothesis, we sequenced complete genomes of 433 EEEV strains collected within the U.S. from 1934 to 2014. Phylogenetic analysis suggested EEEV evolves relatively slowly and that transmission is enzootic in Florida, characterized by higher genetic diversity and long-term local persistence. In contrast, EEEV in New York and Massachusetts were characterized by lower genetic diversity, multiple introductions, and shorter local persistence...
April 4, 2018: Journal of Virology
Barbara H Dobrin, Derrick J Zwickl, Michael J Sanderson
BACKGROUND: The pattern of data availability in a phylogenetic data set may lead to the formation of terraces, collections of equally optimal trees. Terraces can arise in tree space if trees are scored with parsimony or with partitioned, edge-unlinked maximum likelihood. Theory predicts that terraces can be large, but their prevalence in contemporary data sets has never been surveyed. We selected 26 data sets and phylogenetic trees reported in recent literature and investigated the terraces to which the trees would belong, under a common set of inference assumptions...
April 4, 2018: BMC Evolutionary Biology
Liam Stephenson, Yoshua Wakeham, Nick Seidenman, Jarny Choi
Summary: BioPyramid is a python package, which serves as a scaffold for building an online application for the exploration of gene expression data. It is designed for bioinformaticians wishing to quickly share transformed data and interactive analyses with collaborators. Current R-based tools similarly address the need to quickly share "omics"-data in an exploratory format, but these are generally small-scale, single-dataset solutions. Biopyramid is written in python pyramid framework and scalable to address longer-term or more complex projects...
March 29, 2018: Bioinformatics
Shuai Jiang, Yubin Xie, Zhihao He, Ya Zhang, Yuli Zhao, Li Chen, Yueyuan Zheng, Yanyan Miao, Zhixiang Zuo, Jian Ren
Background: Large-scale genome sequencing projects have identified many genetic variants for diverse diseases. A major goal of these projects is to characterize these genetic variants to provide insight into their function and roles in diseases. N6-methyladenosine (m6A) is one of the most abundant RNA modifications in eukaryotes. Recent studies have revealed that aberrant m6A modifications are involved in many diseases. Findings: In this study, we present a user-friendly web server called "m6ASNP" that is dedicated to the identification of genetic variants targeting m6A modification sites...
April 2, 2018: GigaScience
Arthur Zwaenepoel, Tim Diels, David Amar, Thomas Van Parys, Ron Shamir, Yves Van de Peer, Oren Tzfadia
Recent times have seen an enormous growth of "omics" data, of which high-throughput gene expression data are arguably the most important from a functional perspective. Despite huge improvements in computational techniques for the functional classification of gene sequences, common similarity-based methods often fall short of providing full and reliable functional information. Recently, the combination of comparative genomics with approaches in functional genomics has received considerable interest for gene function analysis, leveraging both gene expression based guilt-by-association methods and annotation efforts in closely related model organisms...
2018: Frontiers in Plant Science
Margaret J Grant, Matthew S Loftus, Aiola P Stoja, Dean H Kedes, M Mitchell Smith
By tethering their circular genomes (episomes) to host chromatin, DNA tumor viruses ensure retention and segregation of their genetic material during cell divisions. Despite functional genetic and crystallographic studies, there is little information addressing the 3D structure of these tethers in cells, issues critical for understanding persistent infection by these viruses. Here, we have applied direct stochastic optical reconstruction microscopy (dSTORM) to establish the nanoarchitecture of tethers within cells latently infected with the oncogenic human pathogen, Kaposi's sarcoma-associated herpesvirus (KSHV)...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Bar Lavi, Eli Levy Karin, Tal Pupko, Einat Hazkani-Covo
Perfect short inverted repeats (IRs) are known to be enriched in a variety of bacterial and eukaryotic genomes. Currently, it is unclear whether perfect IRs are conserved over evolutionary time scales. In this study, we aimed to characterize the prevalence and evolutionary conservation of IRs across 20 proteobacterial strains. We first identified IRs in Escherichia coli K-12 substr MG1655 and showed that they are overabundant. We next aimed to test whether this overabundance is reflected in the conservation of IRs over evolutionary time scales...
March 1, 2018: Genome Biology and Evolution
Markus H Kuehn, Rajashree Mishra, Benjamin E Deonovic, Kimberly N Miller, Shana E McCormack, Grant T Liu, Mark J Kupersmith, Michael Wall
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure of unknown cause. IIH has been shown to be associated with female sex as well as obesity. This genome-wide association study was performed to determine whether genetic variants are associated with this condition. METHODS: We analyzed the chromosomal DNA of 95 patients with IIH enrolled in the Idiopathic Intracranial Hypertension Treatment Trial and 95 controls matched on sex, body mass index, and self-reported ethnicity...
March 30, 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
José Luis Alonzo-Velázquez, Salvador Botello-Rionda, Rafael Herrera-Guzmán, Mauricio Carrillo-Tripp
Viruses are the most abundant pathogens affecting all forms of life. A major component of a virus is a protein shell, known as the viral capsid, that encapsulates the genomic material. The fundamental functions of the capsid are to protect and transport the viral genome, and recognize the host cell. Descriptions of this macromolecular complex have been proposed at different scales of approximation. Here, we introduce a methodology to generate a structured volumetric mesh of icosahedral viral capsids (CapsidMesh) based on the atomic positions of their constituents...
March 30, 2018: International Journal for Numerical Methods in Biomedical Engineering
Hannah Weigand, Martina Weiss, Huimin Cai, Yongping Li, Lili Yu, Christine Zhang, Florian Leese
Local adaptation is of fundamental importance for populations to cope with fast, human-mediated environmental changes. In the past, analyses of local adaptation were restricted to few model species. Nowadays, due to the increased affordability of high-throughput sequencing, local adaptation can be studied much easier by searching for patterns of positive selection using genomic data. In the present study, we analysed effects of wastewater treatment plant and ore mining effluents on stream invertebrate populations...
March 27, 2018: Science of the Total Environment
Pratyaydipta Rudra, K Alaine Broadaway, Erin B Ware, Min A Jhun, Lawrence F Bielak, Wei Zhao, Jennifer A Smith, Patricia A Peyser, Sharon L R Kardia, Michael P Epstein, Debashis Ghosh
Many gene mapping studies of complex traits have identified genes or variants that influence multiple phenotypes. With the advent of next-generation sequencing technology, there has been substantial interest in identifying rare variants in genes that possess cross-phenotype effects. In the presence of such effects, modeling both the phenotypes and rare variants collectively using multivariate models can achieve higher statistical power compared to univariate methods that either model each phenotype separately or perform separate tests for each variant...
March 30, 2018: Genetic Epidemiology
Blanca Hernando-Rodríguez, Annmary Paul Erinjeri, María Jesús Rodríguez-Palero, Val Millar, Sara González-Hernández, María Olmedo, Bettina Schulze, Ralf Baumeister, Manuel J Muñoz, Peter Askjaer, Marta Artal-Sanz
BACKGROUND: Advances in automated image-based microscopy platforms coupled with high-throughput liquid workflows have facilitated the design of large-scale screens utilising multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential genes has lagged behind because lethal or sterile mutations pose a bottleneck for high-throughput approaches, and a systematic way to analyse genetic interactions of essential genes in multicellular organisms has been lacking...
March 29, 2018: BMC Biology
Andrew Storfer, Austin Patton, Alexandra K Fraik
As next-generation sequencing data become increasingly available for non-model organisms, a shift has occurred in the focus of studies of the geographic distribution of genetic variation. Whereas landscape genetics studies primarily focus on testing the effects of landscape variables on gene flow and genetic population structure, landscape genomics studies focus on detecting candidate genes under selection that indicate possible local adaptation. Navigating the transition between landscape genomics and landscape genetics can be challenging...
2018: Frontiers in Genetics
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