Stefan R Henz

Max Placnk Institute for Developmental Biology · Department of Molecular Biology

Research interests

  • Interests
    Phylogeny, Assembly, Annotation, Genetic Analysis

Publications

  • 9.43
    Impact points
    Reference-guided assembly of four diverse Arabidopsis thaliana genomes.

    Korbinian Schneeberger, Stephan Ossowski, Felix Ott, Juliane D Klein, Xi Wang, Christa Lanz, Lisa M Smith, Jun Cao, Joffrey Fitz, Norman Warthmann, Stefan R Henz, Daniel H Huson, Detlef Weigel

    Proceedings of the National Academy of Sciences of the United States of America. 06/2011; 108(25):10249-54.

    We present whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125-Mb reference genome sequence released a decade ago. Using a newly developed reference-guided approach, we assembled large contigs from 9 to 42 Gb of Illumina short-read data from the Landsberg e... [more] We present whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125-Mb reference genome sequence released a decade ago. Using a newly developed reference-guided approach, we assembled large contigs from 9 to 42 Gb of Illumina short-read data from the Landsberg erecta (Ler-1), C24, Bur-0, and Kro-0 strains, which have been sequenced as part of the 1,001 Genomes Project for this species. Using alignments against the reference sequence, we first reduced the complexity of the de novo assembly and later integrated reads without similarity to the reference sequence. As an example, half of the noncentromeric C24 genome was covered by scaffolds that are longer than 260 kb, with a maximum of 2.2 Mb. Moreover, over 96% of the reference genome was covered by the reference-guided assembly, compared with only 87% with a complete de novo assembly. Comparisons with 2 Mb of dideoxy sequence reveal that the per-base error rate of the reference-guided assemblies was below 1 in 10,000. Our assemblies provide a detailed, genomewide picture of large-scale differences between A. thaliana individuals, most of which are difficult to access with alignment-consensus methods only. We demonstrate their practical relevance in studying the expression differences of polymorphic genes and show how the analysis of sRNA sequencing data can lead to erroneous conclusions if aligned against the reference genome alone. Genome assemblies, raw reads, and further information are accessible through http://1001genomes.org/projects/assemblies.html.
  • 11.34
    Impact points
    A spatial and temporal map of C. elegans gene expression.

    W Clay Spencer, Georg Zeller, Joseph D Watson, Stefan R Henz, Kathie L Watkins, Rebecca D McWhirter, Sarah Petersen, Vipin T Sreedharan, Christian Widmer, Jeanyoung Jo, Valerie Reinke, Lisa Petrella, Susan Strome, Stephen E Von Stetina, Menachem Katz, Shai Shaham, Gunnar Rätsch, David M Miller

    Genome research. 02/2011; 21(2):325-41.

    The C. elegans genome has been completely sequenced, and the developmental anatomy of this model organism is described at single-cell resolution. Here we utilize strategies that exploit this precisely defined architecture to link gene expression to cell type. We obtained RNAs from specific cells and... [more] The C. elegans genome has been completely sequenced, and the developmental anatomy of this model organism is described at single-cell resolution. Here we utilize strategies that exploit this precisely defined architecture to link gene expression to cell type. We obtained RNAs from specific cells and from each developmental stage using tissue-specific promoters to mark cells for isolation by FACS or for mRNA extraction by the mRNA-tagging method. We then generated gene expression profiles of more than 30 different cells and developmental stages using tiling arrays. Machine-learning-based analysis detected transcripts corresponding to established gene models and revealed novel transcriptionally active regions (TARs) in noncoding domains that comprise at least 10% of the total C. elegans genome. Our results show that about 75% of transcripts with detectable expression are differentially expressed among developmental stages and across cell types. Examination of known tissue- and cell-specific transcripts validates these data sets and suggests that newly identified TARs may exercise cell-specific functions. Additionally, we used self-organizing maps to define groups of coregulated transcripts and applied regulatory element analysis to identify known transcription factor- and miRNA-binding sites, as well as novel motifs that likely function to control subsets of these genes. By using cell-specific, whole-genome profiling strategies, we have detected a large number of novel transcripts and produced high-resolution gene expression maps that provide a basis for establishing the roles of individual genes in cellular differentiation.
  • 9.43
    Impact points
    Receptor-type guanylate cyclase is required for carbon dioxide sensation by Caenorhabditis elegans.

    Elissa A Hallem, W Clay Spencer, Rebecca D McWhirter, Georg Zeller, Stefan R Henz, Gunnar Rätsch, David M Miller, H Robert Horvitz, Paul W Sternberg, Niels Ringstad

    Proceedings of the National Academy of Sciences of the United States of America. 01/2011; 108(1):254-9.

    CO(2) is both a critical regulator of animal physiology and an important sensory cue for many animals for host detection, food location, and mate finding. The free-living soil nematode Caenorhabditis elegans shows CO(2) avoidance behavior, which requires a pair of ciliated sensory neurons, the BAG n... [more] CO(2) is both a critical regulator of animal physiology and an important sensory cue for many animals for host detection, food location, and mate finding. The free-living soil nematode Caenorhabditis elegans shows CO(2) avoidance behavior, which requires a pair of ciliated sensory neurons, the BAG neurons. Using in vivo calcium imaging, we show that CO(2) specifically activates the BAG neurons and that the CO(2)-sensing function of BAG neurons requires TAX-2/TAX-4 cyclic nucleotide-gated ion channels and the receptor-type guanylate cyclase GCY-9. Our results delineate a molecular pathway for CO(2) sensing and suggest that activation of a receptor-type guanylate cyclase is an evolutionarily conserved mechanism by which animals detect environmental CO(2).
  • 34.48
    Impact points
    The genome of Tetranychus urticae reveals herbivorous pest adaptations.

    Miodrag Grbić, Thomas Van Leeuwen, Richard M Clark, Stephane Rombauts, Pierre Rouzé, Vojislava Grbić, Edward J Osborne, Wannes Dermauw, Phuong Cao Thi Ngoc, Félix Ortego, [......], Kristof Demeestere, Stefan R Henz, T Ryan Gregory, Johannes Mathieu, Lou Verdon, Laurent Farinelli, Jeremy Schmutz, Erika Lindquist, René Feyereisen, Yves Van de Peer

    Nature. 01/2011; 479(7374):487-92.

    The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. ... [more] The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the smallest sequenced arthropod genome. Compared with other arthropods, the spider mite genome shows unique changes in the hormonal environment and organization of the Hox complex, and also reveals evolutionary innovation of silk production. We find strong signatures of polyphagy and detoxification in gene families associated with feeding on different hosts and in new gene families acquired by lateral gene transfer. Deep transcriptome analysis of mites feeding on different plants shows how this pest responds to a changing host environment. The T. urticae genome thus offers new insights into arthropod evolution and plant-herbivore interactions, and provides unique opportunities for developing novel plant protection strategies.
  • 29.75
    Impact points
    Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

    Mark B Gerstein, Zhi John Lu, Eric L Van Nostrand, Chao Cheng, Bradley I Arshinoff, Tao Liu, Kevin Y Yip, Rebecca Robilotto, Andreas Rechtsteiner, Kohta Ikegami, [......], X Shirley Liu, Valerie Reinke, Stuart K Kim, LaDeana W Hillier, Steven Henikoff, Fabio Piano, Michael Snyder, Lincoln Stein, Jason D Lieb, Robert H Waterston

    Science (New York, N.Y.). 12/2010; 330(6012):1775-87.

    We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps... [more] We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.
  • 9.43
    Impact points
    Global effects of the small RNA biogenesis machinery on the Arabidopsis thaliana transcriptome.

    Sascha Laubinger, Georg Zeller, Stefan R Henz, Sabine Buechel, Timo Sachsenberg, Jia-Wei Wang, Gunnar Rätsch, Detlef Weigel

    Proceedings of the National Academy of Sciences of the United States of America. 10/2010; 107(41):17466-73.

    In Arabidopsis thaliana, four different dicer-like (DCL) proteins have distinct but partially overlapping functions in the biogenesis of microRNAs (miRNAs) and siRNAs from longer, noncoding precursor RNAs. To analyze the impact of different components of the small RNA biogenesis machinery on the tra... [more] In Arabidopsis thaliana, four different dicer-like (DCL) proteins have distinct but partially overlapping functions in the biogenesis of microRNAs (miRNAs) and siRNAs from longer, noncoding precursor RNAs. To analyze the impact of different components of the small RNA biogenesis machinery on the transcriptome, we subjected dcl and other mutants impaired in small RNA biogenesis to whole-genome tiling array analysis. We compared both protein-coding genes and noncoding transcripts, including most pri-miRNAs, in two tissues and several stress conditions. Our analysis revealed a surprising number of common targets in dcl1 and dcl2 dcl3 dcl4 triple mutants. Furthermore, our results suggest that the DCL1 is not only involved in miRNA action but also contributes to silencing of a subset of transposons, apparently through an effect on DNA methylation.
  • 6.95
    Impact points
    Stress-induced changes in the Arabidopsis thaliana transcriptome analyzed using whole genome tiling arrays.

    Georg Zeller, Stefan R Henz, Christian K Widmer, Timo Sachsenberg, Gunnar Rätsch, Detlef Weigel, Sascha Laubinger

    The Plant journal : for cell and molecular biology. 03/2009;

    Abstract Plant responses to abiotic stresses are accompanied by massive changes in transcriptome composition. To provide a comprehensive view of stress-induced changes in the Arabidopsis thaliana transcriptome, we have used whole-genome tiling arrays to analyze the effects of salt, osmotic, cold and... [more] Abstract Plant responses to abiotic stresses are accompanied by massive changes in transcriptome composition. To provide a comprehensive view of stress-induced changes in the Arabidopsis thaliana transcriptome, we have used whole-genome tiling arrays to analyze the effects of salt, osmotic, cold and heat stress as well as application of the hormone abscisic acid (ABA), an important mediator of stress responses. Among annotated genes in the reference strain Columbia, we have found many stress-responsive genes, including several transcription factor genes as well as pseudogenes and transposons that have been missed in previous analyses with standard expression arrays. In addition, we report hundreds of newly identified, stress-induced transcribed regions. These often overlap with known, annotated genes. The results are accessible through the Arabidopsis thaliana Tiling Array Express (At-TAX) homepage, which provides convenient tools for displaying expression values of annotated genes, as well as visualization of unannotated transcribed regions along each chromosome.
  • 6.63
    Impact points
    At-TAX: a whole genome tiling array resource for developmental expression analysis and transcript identification in Arabidopsis thaliana.

    Sascha Laubinger, Georg Zeller, Stefan Henz, Timo Sachsenberg, Christian Widmer, Naira Naouar, Marnik Vuylsteke, Bernhard Scholkopf, Gunnar Ratsch, Detlef Weigel

    Genome biology. 08/2008; 9(7):R112.

    ABSTRACT: Gene expression maps for model organisms, including Arabidopsis thaliana, have typically been created using gene-centric expression arrays. Here, we describe a comprehensive expression atlas, At-TAX, which is based on whole-genome tiling arrays. We demonstrate that tiling arrays are an acc... [more] ABSTRACT: Gene expression maps for model organisms, including Arabidopsis thaliana, have typically been created using gene-centric expression arrays. Here, we describe a comprehensive expression atlas, At-TAX, which is based on whole-genome tiling arrays. We demonstrate that tiling arrays are an accurate tool for gene expression analysis and identified more than a thousand unannotated transcribed regions. Visualizations of gene expression estimates, transcribed regions and tiling probe measurements are accessible online at the At-TAX homepage.
  • Transcript normalization and segmentation of tiling array data.

    Georg Zeller, Stefan R Henz, Sascha Laubinger, Detlef Weigel, Gunnar Rätsch

    Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 02/2008;

    For the analysis of transcriptional tiling arrays we have developed two methods based on state-of-the-art machine learning algorithms. First, we present a novel transcript normalization technique to alleviate the effect of oligonucleotide probe sequences on hybridization intensity. It is specificall... [more] For the analysis of transcriptional tiling arrays we have developed two methods based on state-of-the-art machine learning algorithms. First, we present a novel transcript normalization technique to alleviate the effect of oligonucleotide probe sequences on hybridization intensity. It is specifically designed to decrease the variability observed for individual probes complementary to the same transcript. Applying this normalization technique to Arabidopsis tiling arrays, we are able to reduce sequence biases and also significantly improve separation in signal intensity between exonic and intronic/intergenic probes. Our second contribution is a method for transcript mapping. It extends an algorithm proposed for yeast tiling arrays to the more challenging task of spliced transcript identification. When evaluated on raw versus normalized intensities our method achieves highest prediction accuracy when segmentation is performed on transcript-normalized tiling array data.
  • Transcript Normalization and Segmentation of Tiling Array Data.

    Georg Zeller, Stefan R. Henz, Sascha Laubinger, Detlef Weigel, Gunnar Rätsch

    Biocomputing 2008, Proceedings of the Pacific Symposium, Kohala Coast, Hawaii, USA, 4-8 January 2008; 01/2008

  • 6.24
    Impact points
    Distinct expression patterns of natural antisense transcripts in Arabidopsis.

    Stefan R Henz, Jason S Cumbie, Kristin D Kasschau, Jan U Lohmann, James C Carrington, Detlef Weigel, Markus Schmid

    Plant physiology. 08/2007; 144(3):1247-55.

    It has been shown that overlapping cis-natural antisense transcripts (cis-NATs) can form a regulatory circuit in which small RNAs derived from one transcript regulate stability of the other transcript, which manifests itself as anticorrelated expression. However, little is known about how widespread... [more] It has been shown that overlapping cis-natural antisense transcripts (cis-NATs) can form a regulatory circuit in which small RNAs derived from one transcript regulate stability of the other transcript, which manifests itself as anticorrelated expression. However, little is known about how widespread antagonistic expression of cis-NATs is. We have determined how frequently cis-NAT pairs, which make up 7.4% of annotated transcription units in the Arabidopsis (Arabidopsis thaliana) genome, show anticorrelated expression patterns. Indeed, global expression profiles of pairs of cis-NATs on average have significantly lower pairwise Pearson correlation coefficients than other pairs of neighboring genes whose transcripts do not overlap. However, anticorrelated expression that is greater than expected by chance is found in only a small number of cis-NAT pairs. The degree of anticorrelation does not depend on the length of the overlap or on the distance of the 5' ends of the transcripts. Consistent with earlier findings, cis-NATs do not exhibit an increased likelihood to give rise to small RNAs, as determined from available small RNA sequences and massively parallel signature sequencing tags. However, the overlapping regions of cis-NATs appeared to be enriched for small RNA loci compared to nonoverlapping regions. Furthermore, expression of cis-NATs was not disproportionately affected in various RNA-silencing mutants. Our results demonstrate that there is a trend toward anticorrelated expression of cis-NAT pairs in Arabidopsis, but currently available data do not produce a strong signature of small RNA-mediated silencing for this process.
  • 4.11
    Impact points
    Opsin gene duplication and diversification in the guppy, a model for sexual selection.

    Margarete Hoffmann, Namita Tripathi, Stefan R Henz, Anna K Lindholm, Detlef Weigel, Felix Breden, Christine Dreyer

    Proceedings. Biological sciences / The Royal Society. 02/2007; 274(1606):33-42.

    Identification of genes that control variation in adaptive characters is a prerequisite for understanding the processes that drive sexual and natural selection. Male coloration and female colour perception play important roles in mate choice in the guppy (Poecilia reticulata), a model organism for s... [more] Identification of genes that control variation in adaptive characters is a prerequisite for understanding the processes that drive sexual and natural selection. Male coloration and female colour perception play important roles in mate choice in the guppy (Poecilia reticulata), a model organism for studies of natural and sexual selection. We examined a potential source for the known variation in colour perception, by analysing genomic and complementary DNA sequences of genes that code for visual pigment proteins. We find high sequence variability, both within and between populations, and expanded copy number for long-wave sensitive (LWS) opsin genes. Alleles with non-synonymous changes that suggest dissimilar spectral tuning properties occur in the same population and even in the same individual, and the high frequency of non-synonymous substitutions argues for diversifying selection acting on these proteins. Therefore, variability in tuning amino acids is partitioned within individuals and populations of the guppy, in contrast to variability for LWS at higher taxonomic levels in cichlids, a second model system for differentiation owing to sexual selection. Since opsin variability parallels the extreme male colour polymorphism within guppy populations, we suggest that mate choice has been a major factor driving the coevolution of opsins and male ornaments in this species.
  • 3.76
    Impact points
    ESTs and EST-linked polymorphisms for genetic mapping and phylogenetic reconstruction in the guppy, Poecilia reticulata.

    Christine Dreyer, Margarete Hoffmann, Christa Lanz, Eva-Maria Willing, Markus Riester, Norman Warthmann, Andrea Sprecher, Namita Tripathi, Stefan R Henz, Detlef Weigel

    BMC genomics. 02/2007; 8:269.

    BACKGROUND: The guppy, Poecilia reticulata, is a well-known model organism for studying inheritance and variation of male ornamental traits as well as adaptation to different river habitats. However, genomic resources for studying this important model were not previously widely available. RESULTS: W... [more] BACKGROUND: The guppy, Poecilia reticulata, is a well-known model organism for studying inheritance and variation of male ornamental traits as well as adaptation to different river habitats. However, genomic resources for studying this important model were not previously widely available. RESULTS: With the aim of generating molecular markers for genetic mapping of the guppy, cDNA libraries were constructed from embryos and different adult organs to generate expressed sequence tags (ESTs). About 18,000 ESTs were annotated according to BLASTN and BLASTX results and the sequence information from the 3' UTRs was exploited to generate PCR primers for re-sequencing of genomic DNA from different wild type strains. By comparison of EST-linked genomic sequences from at least four different ecotypes, about 1,700 polymorphisms were identified, representing about 400 distinct genes. Two interconnected MySQL databases were built to organize the ESTs and markers, respectively. A robust phylogeny of the guppy was reconstructed, based on 10 different nuclear genes. CONCLUSION: Our EST and marker databases provide useful tools for genetic mapping and phylogenetic studies of the guppy.
  • 7.19
    Impact points
    Comparative analysis of Hox downstream genes in Drosophila.

    Stefanie D Hueber, Daniela Bezdan, Stefan R Henz, Martina Blank, Haijia Wu, Ingrid Lohmann

    Development (Cambridge, England). 02/2007; 134(2):381-92.

    Functional diversification of body parts is dependent on the formation of specialized structures along the various body axes. In animals, region-specific morphogenesis along the anteroposterior axis is controlled by a group of conserved transcription factors encoded by the Hox genes. Although it has... [more] Functional diversification of body parts is dependent on the formation of specialized structures along the various body axes. In animals, region-specific morphogenesis along the anteroposterior axis is controlled by a group of conserved transcription factors encoded by the Hox genes. Although it has long been assumed that Hox proteins carry out their function by regulating distinct sets of downstream genes, only a small number of such genes have been found, with very few having direct roles in controlling cellular behavior. We have quantitatively identified hundreds of Hox downstream genes in Drosophila by microarray analysis, and validated many of them by in situ hybridizations on loss- and gain-of-function mutants. One important finding is that Hox proteins, despite their similar DNA-binding properties in vitro, have highly specific effects on the transcriptome in vivo, because expression of many downstream genes respond primarily to a single Hox protein. In addition, a large fraction of downstream genes encodes realizator functions, which directly affect morphogenetic processes, such as orientation and rate of cell divisions, cell-cell adhesion and communication, cell shape and migration, or cell death. Focusing on these realizators, we provide a framework for the morphogenesis of the maxillary segment. As the genomic organization of Hox genes and the interaction of Hox proteins with specific co-factors are conserved in vertebrates and invertebrates, and similar classes of downstream genes are regulated by Hox proteins across the metazoan phylogeny, our findings represent a first step toward a mechanistic understanding of morphological diversification within a species as well as between species.
  • ESTs and EST-linked polymorphisms for genetic mapping and phylogenetic reconstruction in the guppy, Poecilia reticulata

    Christine Dreyer, Margarete Hoffmann, Christa Lanz, Eva-Maria Willing, Markus Riester, Norman Warthmann, Andrea Sprecher, Namita Tripathi, Stefan Henz, Detlef Weigel

    BMC Genomics. 01/2007;

    Abstract Background The guppy, Poecilia reticulata , is a well-known model organism for studying inheritance and variation of male ornamental traits as well as adaptation to different river habitats. However, genomic resources for studying this important model were not previously widely available.... [more] Abstract Background The guppy, Poecilia reticulata , is a well-known model organism for studying inheritance and variation of male ornamental traits as well as adaptation to different river habitats. However, genomic resources for studying this important model were not previously widely available. Results With the aim of generating molecular markers for genetic mapping of the guppy, cDNA libraries were constructed from embryos and different adult organs to generate expressed sequence tags (ESTs). About 18,000 ESTs were annotated according to BLASTN and BLASTX results and the sequence information from the 3' UTRs was exploited to generate PCR primers for re-sequencing of genomic DNA from different wild type strains. By comparison of EST-linked genomic sequences from at least four different ecotypes, about 1,700 polymorphisms were identified, representing about 400 distinct genes. Two interconnected MySQL databases were built to organize the ESTs and markers, respectively. A robust phylogeny of the guppy was reconstructed, based on 10 different nuclear genes. Conclusion Our EST and marker databases provide useful tools for genetic mapping and phylogenetic studies of the guppy.
  • 8.99
    Impact points
    A divergent external loop confers antagonistic activity on floral regulators FT and TFL1.

    Ji Hoon Ahn, David Miller, Victoria J. Winter, Mark J Banfield, Jeong Hwan Lee, So Yeon Yoo, Stefan R Henz, Robert Leo Brady, Detlef Weigel

    The EMBO journal. 03/2006; 25(3):605-14.

    The Arabidopsis genes FT and TERMINAL FLOWER1 (TFL1) encode related proteins with similarity to human Raf kinase inhibitor protein. FT, and likely also TFL1, is recruited to the promoters of floral genes through interaction with FD, a bZIP transcription factor. FT, however, induces flowering, while ... [more] The Arabidopsis genes FT and TERMINAL FLOWER1 (TFL1) encode related proteins with similarity to human Raf kinase inhibitor protein. FT, and likely also TFL1, is recruited to the promoters of floral genes through interaction with FD, a bZIP transcription factor. FT, however, induces flowering, while TFL1 represses flowering. Residues responsible for the opposite activities of FT and TFL1 were mapped by examining plants that overexpress chimeric proteins. A region important in vivo localizes to a 14-amino-acid segment that evolves very rapidly in TFL1 orthologs, but is almost invariant in FT orthologs. Crystal structures show that this segment forms an external loop of variable conformation. The only residue unambiguously distinguishing the FT and TFL1 loops makes a hydrogen bond with a residue near the entrance of a potential ligand-binding pocket in TFL1, but not in FT. This pocket is contacted by a C-terminal peptide, which also contributes to the opposite FT and TFL1 activities. In combination, these results identify a molecular surface likely to be recognized by FT- and/or TFL1-specific interactors.
  • 3.43
    Impact points
    Genome BLAST distance phylogenies inferred from whole plastid and whole mitochondrion genome sequences.

    Alexander F Auch, Stefan R Henz, Barbara R Holland, Markus Göker

    BMC bioinformatics. 02/2006; 7:350.

    BACKGROUND: Phylogenetic methods which do not rely on multiple sequence alignments are important tools in inferring trees directly from completely sequenced genomes. Here, we extend the recently described Genome BLAST Distance Phylogeny (GBDP) strategy to compute phylogenetic trees from all complete... [more] BACKGROUND: Phylogenetic methods which do not rely on multiple sequence alignments are important tools in inferring trees directly from completely sequenced genomes. Here, we extend the recently described Genome BLAST Distance Phylogeny (GBDP) strategy to compute phylogenetic trees from all completely sequenced plastid genomes currently available and from a selection of mitochondrial genomes representing the major eukaryotic lineages. BLASTN, TBLASTX, or combinations of both are used to locate high-scoring segment pairs (HSPs) between two sequences from which pairwise similarities and distances are computed in different ways resulting in a total of 96 GBDP variants. The suitability of these distance formulae for phylogeny reconstruction is directly estimated by computing a recently described measure of "treelikeness", the so-called delta value, from the respective distance matrices. Additionally, we compare the trees inferred from these matrices using UPGMA, NJ, BIONJ, FastME, or STC, respectively, with the NCBI taxonomy tree of the taxa under study. RESULTS: Our results indicate that, at this taxonomic level, plastid genomes are much more valuable for inferring phylogenies than are mitochondrial genomes, and that distances based on breakpoints are of little use. Distances based on the proportion of "matched" HSP length to average genome length were best for tree estimation. Additionally we found that using TBLASTX instead of BLASTN and, particularly, combining TBLASTX and BLASTN leads to a small but significant increase in accuracy. Other factors do not significantly affect the phylogenetic outcome. The BIONJ algorithm results in phylogenies most in accordance with the current NCBI taxonomy, with NJ and FastME performing insignificantly worse, and STC performing as well if applied to high quality distance matrices. delta values are found to be a reliable predictor of phylogenetic accuracy. CONCLUSION: Using the most treelike distance matrices, as judged by their delta values, distance methods are able to recover all major plant lineages, and are more in accordance with Apicomplexa organelles being derived from "green" plastids than from plastids of the "red" type. GBDP-like methods can be used to reliably infer phylogenies from different kinds of genomic data. A framework is established to further develop and improve such methods. delta values are a topology-independent tool of general use for the development and assessment of distance methods for phylogenetic inference.
  • 34.28
    Impact points
    A gene expression map of Arabidopsis thaliana development.

    Markus Schmid, Timothy S Davison, Stefan R Henz, Utz J Pape, Monika Demar, Martin Vingron, Bernhard Schölkopf, Detlef Weigel, Jan U Lohmann

    Nature genetics. 06/2005; 37(5):501-6.

    Regulatory regions of plant genes tend to be more compact than those of animal genes, but the complement of transcription factors encoded in plant genomes is as large or larger than that found in those of animals. Plants therefore provide an opportunity to study how transcriptional programs control ... [more] Regulatory regions of plant genes tend to be more compact than those of animal genes, but the complement of transcription factors encoded in plant genomes is as large or larger than that found in those of animals. Plants therefore provide an opportunity to study how transcriptional programs control multicellular development. We analyzed global gene expression during development of the reference plant Arabidopsis thaliana in samples covering many stages, from embryogenesis to senescence, and diverse organs. Here, we provide a first analysis of this data set, which is part of the AtGenExpress expression atlas. We observed that the expression levels of transcription factor genes and signal transduction components are similar to those of metabolic genes. Examining the expression patterns of large gene families, we found that they are often more similar than would be expected by chance, indicating that many gene families have been co-opted for specific developmental processes.
  • 4.93
    Impact points
    Whole-genome prokaryotic phylogeny.

    Stefan R Henz, Daniel H Huson, Alexander F Auch, Kay Nieselt-Struwe, Stephan C Schuster

    Bioinformatics (Oxford, England). 06/2005; 21(10):2329-35.

    Current understanding of the phylogeny of prokaryotes is based on the comparison of the highly conserved small ssu-rRNA subunit and similar regions. Although such molecules have proved to be very useful phylogenetic markers, mutational saturation is a problem, due to their restricted lengths. Now, a... [more] Current understanding of the phylogeny of prokaryotes is based on the comparison of the highly conserved small ssu-rRNA subunit and similar regions. Although such molecules have proved to be very useful phylogenetic markers, mutational saturation is a problem, due to their restricted lengths. Now, a growing number of complete prokaryotic genomes are available. This paper addresses the problem of determining a prokaryotic phylogeny utilizing the comparison of complete genomes. We introduce a new strategy, GBDP, 'genome blast distance phylogeny', and show that different variants of this approach robustly produce phylogenies that are biologically sound, when applied to 91 prokaryotic genomes. In this approach, first Blast is used to compare genomes, then a distance matrix is computed, and finally a tree- or network-reconstruction method such as UPGMA, Neighbor-Joining, BioNJ or Neighbor-Net is applied.
  • 9.29
    Impact points
    Comprehensive interaction map of the Arabidopsis MADS Box transcription factors.

    Stefan de Folter, Richard G H Immink, Martin Kieffer, Lucie Parenicová, Stefan R Henz, Detlef Weigel, Marco Busscher, Maarten Kooiker, Lucia Colombo, Martin M Kater, Brendan Davies, Gerco C Angenent

    The Plant cell. 05/2005; 17(5):1424-33.

    Interactions between proteins are essential for their functioning and the biological processes they control. The elucidation of interaction maps based on yeast studies is a first step toward the understanding of molecular networks and provides a framework of proteins that possess the capacity and sp... [more] Interactions between proteins are essential for their functioning and the biological processes they control. The elucidation of interaction maps based on yeast studies is a first step toward the understanding of molecular networks and provides a framework of proteins that possess the capacity and specificity to interact. Here, we present a comprehensive plant protein-protein interactome map of nearly all members of the Arabidopsis thaliana MADS box transcription factor family. A matrix-based yeast two-hybrid screen of >100 members of this family revealed a collection of specific heterodimers and a few homodimers. Clustering of proteins with similar interaction patterns pinpoints proteins involved in the same developmental program and provides valuable information about the participation of uncharacterized proteins in these programs. Furthermore, a model is proposed that integrates the floral induction and floral organ formation networks based on the interactions between the proteins involved. Heterodimers between flower induction and floral organ identity proteins were observed, which point to (auto)regulatory mechanisms that prevent the activity of flower induction proteins in the flower.
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