Genome Biology

Uberon, an integrative multi-species anatomy ontology.

Publication Date: 2012 Jan 31 PMID: 22293552
Authors: Mungall, C. J. - Torniai, C. - Gkoutos, G. V. - Lewis, S. E. - Haendel, M. A.
Journal: Genome Biol

ABSTRACT: We present Uberon, an integrated cross-species ontology consisting of over 6500 classes representing a variety of anatomical entities, organized according to traditional anatomical classification criteria. The ontology represents structures in a species-neutral way and includes extensive associations to existing species-centric anatomical ontologies, allowing integration of model organism and human data. Uberon provides a necessary bridge between anatomical structures in different taxa for cross-species inference. It uses novel methods for representing taxonomic variation, and has proved to be essential for translational phenotype analyses. Uberon is available at http://obo.svn.sourceforge.net/viewvc/obo/uberon/releases/2011-09-25/

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SpliceGrapher: Detecting patterns of alternative splicing from RNA-seq data in the context of gene models and EST data.

Publication Date: 2012 Jan 31 PMID: 22293517
Authors: Rogers, M. F. - Thomas, J. - Reddy, A. S. - Ben-Hur, A.
Journal: Genome Biol

ABSTRACT: We propose a method for predicting splice graphs that enhances curated gene models using evidence from RNA-Seq and EST alignments. Results obtained using RNA-Seq experiments in Arabidopsis thaliana show that predictions made by our SpliceGrapher method are more consistent with current gene models than predictions made by TAU and Cufflinks. Furthermore, analysis of plant and human data indicates that the machine learning approach used by SpliceGrapher is useful for discriminating between real and spurious splice sites, and can improve the reliability of detection of alternative splicing. SpliceGrapher is available for download at http://SpliceGrapher.sf.net.

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Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes.

Publication Date: 2012 Jan 31 PMID: 22293439
Authors: St John, J. A. - Braun, E. L. - Isberg, S. R. - Miles, L. G. - Chong, A. Y. - Gongora, J. - Dalzell, P. - Moran, C. - Bed'hom, B. - Abzhanov, A. - Burgess, S. C. - Cooksey, A. M. - Castoe, T. A. - Crawford, N. G. - Densmore, L. D. - Drew, J. C. - Edwards, S. V. - Faircloth, B. C. - Fujita, M. K. - Greenwold, M. J. - Hoffmann, F. G. - Howard, J. M. - Iguchi, T. - Janes, D. E. - Khan, S. Y. - Kohno, S. - de Koning, A. J. - Lance, S. L. - McCarthy, F. M. - McCormack, J. E. - Merchant, M. E. - Peterson, D. G. - Pollock, D. D. - Pourmand, N. - Raney, B. J. - Roessler, K. A. - Sanford, J. R. - Sawyer, R. H. - Schmidt, C. J. - Triplett, E. W. - Tuberville, T. D. - Venegas-Anaya, M. - Howard, J. T. - Jarvis, E. D. - Guillette, L. J. Jr - Glenn, T. C. - Green, R. E. - Ray, D. A.
Journal: Genome Biol

ABSTRACT: The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial (Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described.

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Dissecting the regulatory architecture of gene expression QTLs.

Publication Date: 2012 Jan 31 PMID: 22293038
Authors: Gaffney, D. J. - Veyrieras, J. B. - Degner, J. F. - Roger, P. R. - Pai, A. A. - Crawford, G. E. - Stephens, M. - Gilad, Y. - Pritchard, J. K.
Journal: Genome Biol

ABSTRACT: BACKGROUND: Expression quantitative trait loci (eQTLs) are likely to play an important role in the genetics of complex traits; however their functional basis remains poorly understood. Using the HapMap lymphoblastoid cell lines, we combine 1000 Genomes genotypes and an extensive catalogue of human functional elements to investigate the biological mechanisms that eQTLs perturb. RESULTS: We use a Bayesian hierarchical model to estimate the enrichment of eQTLs in a wide variety of regulatory annotations. We find that ~40% of eQTLs occur in open chromatin, and that they are particularly enriched in transcription factor binding sites, suggesting that many directly impact protein-DNA interactions. Analysis of core promoter regions shows that eQTLs also frequently disrupt some known core promoter motifs but, surprisingly, are not enriched in other well-known motifs such as the TATA box. We also show that information from regulatory annotations alone, when weighted by the hierarchical model, can provide a meaningful ranking of the SNPs that are most likely to drive gene expression variation. CONCLUSIONS: Our study demonstrates how regulatory annotation and the association signal derived from eQTL-mapping can be combined into a single framework. We used this approach to further our understanding of the biology that drives human gene expression variation, and of the putatively causal SNPs that underlie it.

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MetaMerge: scaling up genome-scale metabolic reconstructions, with application to Mycobacterium tuberculosis.

Publication Date: 2012 Jan 31 PMID: 22292986
Authors: Chindelevitch, L. - Stanley, S. - Hung, D. - Regev, A. - Berger, B.
Journal: Genome Biol

ABSTRACT: Reconstructed models of metabolic networks are widely used for studying metabolism in various organisms. Many different reconstructions of the same organism often exist concurrently, forcing researchers to choose one of them at the exclusion of the others. We describe MetaMerge, an algorithm for semi-automatically reconciling a pair of existing metabolic network reconstructions into a single metabolic network model. We use MetaMerge to combine two published metabolic networks for Mycobacterium tuberculosis into a single network which allows many reactions that could not be active in the individual models to become active, and predicts essential genes with a higher positive predictive value.

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Dynamic systems.

Publication Date: 2012 Jan 30 PMID: 22289510
Authors: Bakal, C.
Journal: Genome Biol

ABSTRACT: A report of the Wellcome Trust Functional Genomics and Systems Biology Conference, Hinxton, UK, 29 November to 1 December 2011.

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Low-cost sequencing opens new insights into diverse plant genomes.

Publication Date: 2012 Jan 30 PMID: 22289505
Authors: Birnbaum, K. D.
Journal: Genome Biol

ABSTRACT: A report on the Plant Genomes and Biotechnology: From Genes to Networks meeting, held at Cold Spring Harbor Laboratory, 30 November to 3 December 2011.

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The dog particle.

Publication Date: 2012 Jan 30 PMID: 22289440
Authors: Petsko, G. A.
Journal: Genome Biol

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Co-survival of the fittest few: mosaic amplification of receptor tyrosine kinases in glioblastoma.

Publication Date: 2012 Jan 30 PMID: 22289423
Authors: Chen, F. - Ding, L.
Journal: Genome Biol

ABSTRACT: Mosaic amplification of receptor tyrosine kinases in glioblastoma suggests that tumor cells with different progression driver mutations may coevolve rather than compete during clonal evolution.

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Whack-an-E. coli with the morbidostat.

Publication Date: 2012 Jan 27 PMID: 22283927
Authors: Fridman, O. - Goldberg, A. - Balaban, N. Q.
Journal: Genome Biol

ABSTRACT: Using a device termed the 'morbidostat', a recent study sheds new light on the determinism of genetic and phenotypic trajectories leading to high antibiotic resistance.

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DNA-protein interactions in high definition.

Publication Date: 2012 Jan 27 PMID: 22283870
Authors: Mendenhall, E. M. - Bernstein, B. E.
Journal: Genome Biol

ABSTRACT: An elegant, genome-wide approach to define the precise DNA sequences bound by transcription factors has been developed by Rhee and Pugh.

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A genome triplication associated with early diversification of the core eudicots.

Publication Date: 2012 Jan 26 PMID: 22280555
Authors: Jiao, Y. - Leebens-Mack, J. - Ayyampalayam, S. - Bowers, J. E. - McKain, M. R. - McNeal, J. - Rolf, M. - Ruzicka, D. R. - Wafula, E. - Wickett, N. J. - Wu, X. - Zhang, Y. - Wang, J. - Zhang, Y. - Carpenter, E. J. - Deyholos, M. K. - Kutchan, T. M. - Chanderbali, A. S. - Soltis, P. S. - Stevenson, D. W. - McCombie, R. - Pires, C. J. - Wong, G. K. - Soltis, D. E. - Depamphilis, C. W.
Journal: Genome Biol

ABSTRACT: BACKGROUND: Although it is agreed that a major polyploidy event, gamma, occurred within the eudicots, the phylogenetic placement of the event remains unclear. RESULTS: To determine when this polyploidization occurred relative to speciation events in angiosperm history, we employed a phylogenomic approach to investigate the timing of gene set duplications located on syntenic gamma blocks. 769 putative gene families were populated with large sets of homologs obtained from public transcriptomes of basal angiosperms, magnoliids, asterids, and more than 91.8 gigabases of new Next-Generation transcriptome sequences of non-grass monocots and basal eudicots. The overwhelming majority (95%) of well-resolved gamma duplications was placed before the separation of rosids and asterids and after the split of monocots and eudicots, providing strong evidence that the gamma polyploidy event occurred early in eudicot evolution. Further, the majority of gene duplications was placed after the divergence of the Ranunculales and core eudicots, indicating that the gamma appears to be restricted to core eudicots. Molecular dating estimates indicate that the duplication events were intensely concentrated around 117 million years ago. CONCLUSIONS: The rapid radiation of core eudicot lineages that gave rise to nearly 75% of angiosperm species appears to have occurred coincidentally or shortly following the gamma triplication event. Reconciliation of gene trees with a species phylogeny can elucidate the timing of major events in genome evolution, even when genome sequences are only available for a subset of species represented in the gene trees. Comprehensive transcriptome datasets are valuable complements to genome sequences for high-resolution phylogenomic analysis.

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Implications for health and disease in the genetic signature of the Ashkenazi Jewish population.

Publication Date: 2012 Jan 25 PMID: 22277159
Authors: Guha, S. - Rosenfeld, J. A. - Malhotra, A. K. - Lee, A. T. - Gregersen, P. K. - Kane, J. M. - Pe'er, I. - Darvasi, A. - Lencz, T.
Journal: Genome Biol

ABSTRACT: BACKGROUND: Relatively small, reproductively isolated populations with reduced genetic diversity may have advantages for genomewide association mapping in disease genetics. The Ashkenazi Jewish population represents a unique population for study based on its recent (<1000 year) history of a limited number of founders, population bottlenecks and tradition of marriage within the community. We genotyped more than 1300 Ashkenazi Jewish healthy volunteers from the Hebrew University Genetic Resource with the Illumina HumanOmni1-Quad platform. Comparison of the genotyping data with that of neighboring European and Asian populations enabled the Ashkenazi Jewish-specific component of the variance to be characterized with respect to disease-relevant alleles and pathways. RESULTS: Using clustering, principal components, and pairwise genetic distance as converging approaches, we identified an Ashkenazi Jewish-specific genetic signature that differentiated these subjects from both European and Middle Eastern samples. Most notably, gene ontology analysis of the Ashkenazi Jewish genetic signature revealed an enrichment of genes functioning in transepithelial chloride transport, such as CFTR, and in equilibrioception, potentially shedding light on cystic fibrosis, Usher syndrome and other diseases over-represented in the Ashkenazi Jewish population. Results also impact risk profiles for autoimmune and metabolic disorders in this population. Finally, residual intra-Ashkenazi population structure was minimal, primarily determined by Class 1 MHC alleles, and not related to host country of origin. CONCLUSIONS: The Ashkenazi Jewish population is of potential utility in disease-mapping studies due to its relative homogeneity and distinct genomic signature. Results suggest that Ashkenazi-associated disease genes may be components of population-specific genomic differences in key functional pathways.

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Transcriptional enhancers in development and disease.

Publication Date: 2012 Jan 23 PMID: 22269347
Authors: Sakabe, N. J. - Savic, D. - Nobrega, M. A.
Journal: Genome Biol

ABSTRACT: Distal transcription enhancers are cis-regulatory elements that promote gene expression, enabling spatiotemporal control of genetic programs such as those required in metazoan developmental processes. Because of their importance, their disruption can lead to disease.

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What is complex about complex disorders?

Publication Date: 2012 Jan 23 PMID: 22269335
Authors: Mitchell, K. J.
Journal: Genome Biol

ABSTRACT: Rather than being polygenic, complex disorders probably represent umbrella terms for collections of conditions caused by rare, recent mutations in any of a large number of different genes.

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Genetic adaptation to high altitude in the Ethiopian highlands.

Publication Date: 2012 Jan 20 PMID: 22264333
Authors: Scheinfeldt, L. B. - Soi, S. - Thompson, S. - Ranciaro, A. - Meskel, D. W. - Beggs, W. - Lambert, C. - Jarvis, J. P. - Abate, D. - Belay, G. - Tishkoff, S. A.
Journal: Genome Biol

ABSTRACT: BACKGROUND: Genomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high and low altitude populations living in Ethiopia for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome-wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude. RESULTS: We have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high and low altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels. CONCLUSIONS: We highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia.

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