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Qanbari S.,University of Gottingen | Strom T.M.,Helmholtz Center Munich | Haberer G.,Institute of Bioinformatics and Systems Biology | Weigend S.,Institute of Farm Animal Genetics | And 6 more authors.
PLoS ONE | Year: 2012

In most studies aimed at localizing footprints of past selection, outliers at tails of the empirical distribution of a given test statistic are assumed to reflect locus-specific selective forces. Significance cutoffs are subjectively determined, rather than being related to a clear set of hypotheses. Here, we define an empirical p-value for the summary statistic by means of a permutation method that uses the observed SNP structure in the real data. To illustrate the methodology, we applied our approach to a panel of 2.9 million autosomal SNPs identified from re-sequencing a pool of 15 individuals from a brown egg layer line. We scanned the genome for local reductions in heterozygosity, suggestive of selective sweeps. We also employed a modified sliding window approach that accounts for gaps in the sequence and increases scanning resolution by moving the overlapping windows by steps of one SNP only, and suggest to call this a "creeping window" strategy. The approach confirmed selective sweeps in the region of previously described candidate genes, i.e. TSHR, PRL, PRLHR, INSR, LEPR, IGF1, and NRAMP1 when used as positive controls. The genome scan revealed 82 distinct regions with strong evidence of selection (genome-wide p-value<0.001), including genes known to be associated with eggshell structure and immune system such as CALB1 and GAL cluster, respectively. A substantial proportion of signals was found in poor gene content regions including the most extreme signal on chromosome 1. The observation of multiple signals in a highly selected layer line of chicken is consistent with the hypothesis that egg production is a complex trait controlled by many genes. © 2012 Qanbari et al. Source

Laaser I.,Helmholtz Center for Environmental Research | Theis F.J.,Institute of Bioinformatics and Systems Biology | De Angelis M.H.,Helmholtz Center for Environmental Research | De Angelis M.H.,TU Munich | And 3 more authors.
OMICS A Journal of Integrative Biology | Year: 2011

Over 90% of human genes produce more than one mRNA by alternative splicing (AS). Human UTY (ubiquitously transcribed tetratricopeptide repeat protein on the chromosome Y) has six mRNA-transcripts. UTY is subject to interdisciplinary approaches such as Y chromosomal genetics or development of leukemia immunotherapy based on UTY-specific peptides. Investigating UTY expression in a normal and leukemic setting we discovered an exceptional splicing phenomenon fostering huge transcript diversity. Transcript sequencing identified 90 novel AS-events being almost randomly combined in 284 new transcripts. We uncovered a novel system of transcript architecture and genomic organization in UTY. On a basis of a new UTY-splicing multigraph including a mathematical model we calculated the theoretical yield to exceed 1.3 billion distinct transcripts. To our knowledge, this is the greatest estimated transcript diversity by AS. On protein level we demonstrated interaction of AS-derived proteins with new interactors by yeast-two-hybrid assay. For translational research we predicted new UTY-peptide candidates for leukemia therapy development. Our study provides new insights into the complexity of human alternative splicing and its potential contribution to the transcript diversity of the transcriptome. Copyright © 2011, Mary Ann Liebert, Inc. Source

Kaufmann S.,TU Munich | Frishman D.,TU Munich | Frishman D.,Institute of Bioinformatics and Systems Biology | Frishman D.,Saint Petersburg State Polytechnic University
PLoS ONE | Year: 2014

High-quality mapping of genomic regions and genes between two organisms is an indispensable prerequisite for evolutionary analyses and comparative genomics. Existing approaches to this problem focus on either delineating orthologs or finding extended sequence regions of common evolutionary origin (syntenic blocks). We propose SyntenyMapper, a novel tool for refining predefined syntenic regions. SyntenyMapper creates a set of blocks with conserved gene order between two genomes and finds all minor rearrangements that occurred since the evolutionary split of the two species considered. We also present TrackMapper, a SyntenyMapper-based tool that allows users to directly compare genome features, such as histone modifications, between two organisms, and identify genes with highly conserved features. We demonstrate SyntenyMapper's advantages by conducting a large-scale analysis of micro-rearrangements within syntenic regions of 25 eukaryotic species. Unsurprisingly, the number and length of syntenic regions is correlated with evolutionary distance, while the number of micro-rearrangements depends only on the size of the harboring region. On the other hand, the size of rearranged regions remains relatively constant regardless of the evolutionary distance between the organisms, implying a length constraint in the rearrangement process. SyntenyMapper is a useful software tool for both large-scale and gene-centric genome comparisons. ©2014 Kaufmann Frishman. Source

Ko L.-W.,Institute of Bioinformatics and Systems Biology | Ko L.-W.,National Chiao Tung University
Proceedings - 2015 IEEE Symposium Series on Computational Intelligence, SSCI 2015 | Year: 2015

Hybrid Brain Computer Interface (BCI) is gaining attention as it can provide better performance or increase the number of user commands to control an external device. Hybrid BCI system using Motor imagery (MI) and Steady-state visually evoked potential (SSVEP) is one such system. Maintaining the performance during channel reduction is important in practical applications. In this paper we propose a combined feature extraction method using Canonical Correlation Analysis (CCA) and Common Frequency Pattern (CFP) method, where the features obtained from these methods were combined for classification. We used LDC and PARZEN for estimating the classification accuracy for the proposed method and individual method. Highest accuracy of 96.1 % is obtained for combined feature method (CCA+CFP). Whereas, the accuracy is 89.6% with CCA and 91.6% with CFP method. A significance test has shown that the performance of the proposed method is significantly different from both the individual methods (p < 0.05). © 2015 IEEE. Source

Schwab S.,Institute of Epidemiology II | Zierer A.,Institute of Epidemiology II | Schneider A.,Institute of Epidemiology II | Heier M.,Institute of Epidemiology II | And 7 more authors.
British Journal of Nutrition | Year: 2015

The aim of the present study was to examine the association between intake of five common antioxidative nutrients from supplements and medications (vitamin E, vitamin C, carotenoids, Se, and Zn) and levels of high-sensitivity C-reactive protein (hs-CRP) in the general population. For this purpose, a total of 2924 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006-8) were investigated cross-sectionally. Intake of dietary supplements and medication during the last 7 d was recorded in a personal interview, when participants were asked to show product packages of ingested preparations. Linear regression models were calculated; first, the exposure to regular nutrient intake was treated with a binary response (yes/no); then regularly ingested amounts were divided into quartiles to examine dose-response relationships. Effect of single v. combined supplementation of antioxidants was assessed through the inclusion of interaction terms into the models. Regular intake of any of the five investigated antioxidants per se was not associated with hs-CRP levels. However, dose-response analyses revealed that participants who regularly ingested more than 78 mg vitamin E/d, which corresponds to the upper quartile, had 22 % lower hs-CRP levels (95 % CI 0·63, 0·97) compared to those of persons who were not exposed to any vitamin E supplementation. Stratified analyses showed that this association was found only in persons who took vitamin E in combination with other antioxidants. The combined supplementation of vitamin E with other antioxidants could thus be a promising strategy for the prevention of inflammation-related diseases in the general population, if further studies could confirm that the proposed association is causal. © 2015 The Authors. Source

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