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  • 1. Abreu, Ilka N.
    et al.
    Johansson, Annika I.
    Sokolowska, Katarzyna
    Niittylä, Totte
    Sundberg, Björn
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    A metabolite roadmap of the wood-forming tissue in Populus tremula2020In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 228, no 5, p. 1559-1572Article in journal (Refereed)
    Abstract [en]

    Wood, or secondary xylem, is the product of xylogenesis, a developmental process that begins with the proliferation of cambial derivatives and ends with mature xylem fibers and vessels with lignified secondary cell walls. Fully mature xylem has undergone a series of cellular processes, including cell division, cell expansion, secondary wall formation, lignification and programmed cell death. A complex network of interactions between transcriptional regulators and signal transduction pathways controls wood formation. However, the role of metabolites during this developmental process has not been comprehensively characterized. To evaluate the role of metabolites during wood formation, we performed a high spatial resolution metabolomics study of the wood-forming zone of Populus tremula, including laser dissected aspen ray and fiber cells. We show that metabolites show specific patterns within the wood-forming zone, following the differentiation process from cell division to cell death. The data from profiled laser dissected aspen ray and fiber cells suggests that these two cell types host distinctly different metabolic processes. Furthermore, by integrating previously published transcriptomic and proteomic profiles generated from the same trees, we provide an integrative picture of molecular processes, for example, deamination of phenylalanine during lignification is of critical importance for nitrogen metabolism during wood formation.

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  • 2. Baba, Kyoko
    et al.
    Karlberg, Anna
    Schmidt, Julien
    Schrader, Jarmo
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Bako, Laszlo
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Bhalerao, Rishikesh P
    Activity-dormancy transition in the cambial meristem involves stage-specific modulation of auxin response in hybrid aspen.2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 8, p. 3418-23Article in journal (Refereed)
    Abstract [en]

    The molecular basis of short-day-induced growth cessation and dormancy in the meristems of perennial plants (e.g., forest trees growing in temperate and high-latitude regions) is poorly understood. Using global transcript profiling, we show distinct stage-specific alterations in auxin responsiveness of the transcriptome in the stem tissues during short-day-induced growth cessation and both the transition to and establishment of dormancy in the cambial meristem of hybrid aspen trees. This stage-specific modulation of auxin signaling appears to be controlled via distinct mechanisms. Whereas the induction of growth cessation in the cambium could involve induction of repressor auxin response factors (ARFs) and down-regulation of activator ARFs, dormancy is associated with perturbation of the activity of the SKP-Cullin-F-box(TIR) (SCF(TIR)) complex, leading to potential stabilization of repressor auxin (AUX)/indole-3-acetic acid (IAA) proteins. Although the role of hormones, such as abscisic acid (ABA) and gibberellic acid (GA), in growth cessation and dormancy is well established, our data now implicate auxin in this process. Importantly, in contrast to most developmental processes in which regulation by auxin involves changes in cellular auxin contents, day-length-regulated induction of cambial growth cessation and dormancy involves changes in auxin responses rather than auxin content.

  • 3.
    Björkholm, Patrik
    et al.
    The Linnaeus Centre for Bioinformatics, Uppsala University, Uppsala.
    Daniluk, Pawel
    Department of Biophysics, Faculty of Physics, University of Warsaw, Warsaw, Poland.
    Kryshtafovych, Andriy
    UC Davis Genome Centre, UC Davis, USA.
    Fidelis, Krzysztof
    UC Davis Genome Centre, UC Davis, USA.
    Andersson, Robin
    The Linnaeus Centre for Bioinformatics, Uppsala University, Uppsala.
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Using multi-data hidden Markov models trained on local neighborhoods of protein structure to predict residue-residue contacts.2009In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 25, no 10, p. 1264-1270Article in journal (Refereed)
    Abstract [en]

    MOTIVATION: Correct prediction of residue-residue contacts in proteins that lack good templates with known structure would take ab initio protein structure prediction a large step forward. The lack of correct contacts, and in particular long-range contacts, is considered the main reason why these methods often fail. RESULTS: We propose a novel hidden Markov model (HMM)-based method for predicting residue-residue contacts from protein sequences using as training data homologous sequences, predicted secondary structure and a library of local neighborhoods (local descriptors of protein structure). The library consists of recurring structural entities incorporating short-, medium- and long-range interactions and is general enough to reassemble the cores of nearly all proteins in the PDB. The method is tested on an external test set of 606 domains with no significant sequence similarity to the training set as well as 151 domains with SCOP folds not present in the training set. Considering the top 0.2 x L predictions (L = sequence length), our HMMs obtained an accuracy of 22.8% for long-range interactions in new fold targets, and an average accuracy of 28.6% for long-, medium- and short-range contacts. This is a significant performance increase over currently available methods when comparing against results published in the literature.

  • 4.
    Curci, Pasquale Luca
    et al.
    Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, Ghent, Belgium; VIB Center for Plant Systems Biology, Technologiepark 71, Ghent, Belgium; Institute of Biosciences and Bioresources, National Research Council (CNR), Via Amendola 165/A, Bari, Italy.
    Zhang, Jie
    Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, Ghent, Belgium; VIB Center for Plant Systems Biology, Technologiepark 71, Ghent, Belgium.
    Mähler, Niklas
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Seyfferth, Carolin
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, Ghent, Belgium; VIB Center for Plant Systems Biology, Technologiepark 71, Ghent, Belgium.
    Mannapperuma, Chanaka
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Diels, Tim
    Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, Ghent, Belgium; VIB Center for Plant Systems Biology, Technologiepark 71, Ghent, Belgium.
    Van Hautegem, Tom
    Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, Ghent, Belgium; VIB Center for Plant Systems Biology, Technologiepark 71, Ghent, Belgium.
    Jonsen, David
    SweTree Technologies AB, Skogsmarksgränd 7, Umeå, Sweden.
    Street, Nathaniel
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Hertzberg, Magnus
    SweTree Technologies AB, Umeå, Sweden.
    Nilsson, Ove
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Forest Genetics and Plant Physiology, Umeå Plant Science Centre (UPSC), Swedish University of Agricultural Sciences, Umeå, Sweden.
    Inzé, Dirk
    Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, Ghent, Belgium; VIB Center for Plant Systems Biology, Technologiepark 71, Ghent, Belgium.
    Nelissen, Hilde
    Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, Ghent, Belgium; VIB Center for Plant Systems Biology, Technologiepark 71, Ghent, Belgium.
    Vandepoele, Klaas
    Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, Ghent, Belgium; VIB Center for Plant Systems Biology, Technologiepark 71, Ghent, Belgium; Bioinformatics Institute Ghent, Ghent University, Technologiepark 71, Ghent, Belgium.
    Identification of growth regulators using cross-species network analysis in plants2022In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 190, no 4, p. 2350-2365Article in journal (Refereed)
    Abstract [en]

    With the need to increase plant productivity, one of the challenges plant scientists are facing is to identify genes that play a role in beneficial plant traits. Moreover, even when such genes are found, it is generally not trivial to transfer this knowledge about gene function across species to identify functional orthologs. Here, we focused on the leaf to study plant growth. First, we built leaf growth transcriptional networks in Arabidopsis (Arabidopsis thaliana), maize (Zea mays), and aspen (Populus tremula). Next, known growth regulators, here defined as genes that when mutated or ectopically expressed alter plant growth, together with cross-species conserved networks, were used as guides to predict novel Arabidopsis growth regulators. Using an in-depth literature screening, 34 out of 100 top predicted growth regulators were confirmed to affect leaf phenotype when mutated or overexpressed and thus represent novel potential growth regulators. Globally, these growth regulators were involved in cell cycle, plant defense responses, gibberellin, auxin, and brassinosteroid signaling. Phenotypic characterization of loss-of-function lines confirmed two predicted growth regulators to be involved in leaf growth (NPF6.4 and LATE MERISTEM IDENTITY2). In conclusion, the presented network approach offers an integrative cross-species strategy to identify genes involved in plant growth and development.

  • 5.
    Delhomme, Nicolas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Sundström, Görel
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden.
    Zamani, Neda
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden.
    Lantz, Henrik
    Lin, Yao-Cheng
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Norwegian Univ Life Sci, Dept Chem Biotechnol & Food Sci, As, Norway.
    Hoppner, Marc P.
    Jern, Patric
    Van de Peer, Yves
    Lundeberg, Joakim
    Grabherr, Manfred G.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Serendipitous Meta-Transcriptomics: The Fungal Community of Norway Spruce (Picea abies)2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 9, article id e0139080Article in journal (Refereed)
    Abstract [en]

    After performing de novo transcript assembly of >1 billion RNA-Sequencing reads obtained from 22 samples of different Norway spruce (Picea abies) tissues that were not surface sterilized, we found that assembled sequences captured a mix of plant, lichen, and fungal transcripts. The latter were likely expressed by endophytic and epiphytic symbionts, indicating that these organisms were present, alive, and metabolically active. Here, we show that these serendipitously sequenced transcripts need not be considered merely as contamination, as is common, but that they provide insight into the plant's phyllosphere. Notably, we could classify these transcripts as originating predominantly from Dothideomycetes and Leotiomycetes species, with functional annotation of gene families indicating active growth and metabolism, with particular regards to glucose intake and processing, as well as gene regulation.

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  • 6.
    Fahlén, Jessica
    et al.
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Landfors, Mattias
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Freyhult, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Bylesjö, Max
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Bioinformatics strategies for cDNA-microarray data processing2009In: Batch effects and noise in microarray experiments: sources and solutions / [ed] Scherer, Andreas, Wiley and Sons , 2009, 1, , p. 272p. 61-74Chapter in book (Other academic)
    Abstract [en]

    

    Pre-processing plays a vital role in cDNA-microarray data analysis. Without proper pre-processing it is likely that the biological conclusions will be misleading. However, there are many alternatives and in order to choose a proper pre-processing procedure it is necessary to understand the effect of different methods. This chapter discusses several pre-processing steps, including image analysis, background correction, normalization, and filtering. Spike-in data are used to illustrate how different procedures affect the analytical ability to detect differentially expressed genes and estimate their regulation. The result shows that pre-processing has a major impact on both the experiment’s sensitivity andits bias. However, general recommendations are hard to give, since pre-processing consists of several actions that are highly dependent on each other. Furthermore, it is likely that pre-processing have a major impact on downstream analysis, such as clustering and classification, and pre-processing methods should be developed and evaluated with this in mind.

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  • 7. Felten, Judith
    et al.
    Vahala, Jorma
    Love, Jonathan
    Gorzsás, András
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ruggeberg, Markus
    Delhomme, Nicolas
    Lesniewska, Joanna
    Kangasjarvi, Jaakko
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences,Ås, Norway.
    Mellerowicz, Ewa J.
    Sundberg, Bjorn
    Ethylene signaling induces gelatinous layers with typical features of tension wood in hybrid aspen2018In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 218, no 3, p. 999-1014Article in journal (Refereed)
    Abstract [en]

    The phytohormone ethylene impacts secondary stem growth in plants by stimulating cambial activity, xylem development and fiber over vessel formation. We report the effect of ethylene on secondary cell wall formation and the molecular connection between ethylene signaling and wood formation. We applied exogenous ethylene or its precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to wild-type and ethylene-insensitive hybrid aspen trees (Populus tremulaxtremuloides) and studied secondary cell wall anatomy, chemistry and ultrastructure. We furthermore analyzed the transcriptome (RNA Seq) after ACC application to wild-type and ethylene-insensitive trees. We demonstrate that ACC and ethylene induce gelatinous layers (G-layers) and alter the fiber cell wall cellulose microfibril angle. G-layers are tertiary wall layers rich in cellulose, typically found in tension wood of aspen trees. A vast majority of transcripts affected by ACC are downstream of ethylene perception and include a large number of transcription factors (TFs). Motif-analyses reveal potential connections between ethylene TFs (Ethylene Response Factors (ERFs), ETHYLENE INSENSITIVE 3/ETHYLENE INSENSITIVE3-LIKE1 (EIN3/EIL1)) and wood formation. G-layer formation upon ethylene application suggests that the increase in ethylene biosynthesis observed during tension wood formation is important for its formation. Ethylene-regulated TFs of the ERF and EIN3/EIL1 type could transmit the ethylene signal.

  • 8.
    Freyhult, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Önskog, Jenny
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Social Sciences, Department of Statistics.
    Challenges in microarray class discovery: a comprehensive examination of normalization, gene selection and clustering2010In: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 11, article id 503Article in journal (Refereed)
    Abstract [en]

    Background: Cluster analysis, and in particular hierarchical clustering, is widely used to extract information from gene expression data. The aim is to discover new classes, or sub-classes, of either individuals or genes. Performing a cluster analysis commonly involve decisions on how to; handle missing values, standardize the data and select genes. In addition, pre processing, involving various types of filtration and normalization procedures, can have an effect on the ability to discover biologically relevant classes. Here we consider cluster analysis in a broad sense and perform a comprehensive evaluation that covers several aspects of cluster analyses, including normalization.

    Result: We evaluated 2780 cluster analysis methods on seven publicly available 2-channel microarray data sets with common reference designs. Each cluster analysis method differed in data normalization (5 normalizations were considered), missing value imputation (2), standardization of data (2), gene selection (19) or clustering method (11). The cluster analyses are evaluated using known classes, such as cancer types, and the adjusted Rand index. The performances of the different analyses vary between the data sets and it is difficult to give general recommendations. However, normalization, gene selection and clustering method are all variables that have a significant impact on the performance. In particular, gene selection is important and it is generally necessary to include a relatively large number of genes in order to get good performance. Selecting genes with high standard deviation or using principal component analysis are shown to be the preferred gene selection methods. Hierarchical clustering using Ward's method, k-means clustering and Mclust are the clustering methods considered in this paper that achieves the highest adjusted Rand. Normalization can have a significant positive impact on the ability to cluster individuals, and there are indications that background correction is preferable, in particular if the gene selection is successful. However, this is an area that needs to be studied further in order to draw any general conclusions.

    Conclusions: The choice of cluster analysis, and in particular gene selection, has a large impact on the ability to cluster individuals correctly based on expression profiles. Normalization has a positive effect, but the relative performance of different normalizations is an area that needs more research. In summary, although clustering, gene selection and normalization are considered standard methods in bioinformatics, our comprehensive analysis shows that selecting the right methods, and the right combinations of methods, is far from trivial and that much is still unexplored in what is considered to be the most basic analysis of genomic data.

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  • 9.
    Gandla, Madhavi Latha
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mähler, Niklas
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Escamez, Sacha
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Sweden.
    Skotare, Tomas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Obudulu, Ogonna
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Möller, Linus
    SweTree Technologies, Umeå, Sweden.
    Abreu, Ilka N.
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Bygdell, Joakim
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hertzberg, Magnus
    SweTree Technologies, Umeå, Sweden.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Wingsle, Gunnar
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Jönsson, Leif J.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Overexpression of vesicle-associated membrane protein PttVAP27-17 as a tool to improve biomass production and the overall saccharification yields in Populus trees2021In: Biotechnology for Biofuels, ISSN 1754-6834, E-ISSN 1754-6834, Vol. 14, no 1, article id 43Article in journal (Refereed)
    Abstract [en]

    Background: Bioconversion of wood into bioproducts and biofuels is hindered by the recalcitrance of woody raw material to bioprocesses such as enzymatic saccharification. Targeted modification of the chemical composition of the feedstock can improve saccharification but this gain is often abrogated by concomitant reduction in tree growth.

    Results: In this study, we report on transgenic hybrid aspen (Populus tremula × tremuloides) lines that showed potential to increase biomass production both in the greenhouse and after 5 years of growth in the field. The transgenic lines carried an overexpression construct for Populus tremula × tremuloides vesicle-associated membrane protein (VAMP)-associated protein PttVAP27-17 that was selected from a gene-mining program for novel regulators of wood formation. Analytical-scale enzymatic saccharification without any pretreatment revealed for all greenhouse-grown transgenic lines, compared to the wild type, a 20–44% increase in the glucose yield per dry weight after enzymatic saccharification, even though it was statistically significant only for one line. The glucose yield after enzymatic saccharification with a prior hydrothermal pretreatment step with sulfuric acid was not increased in the greenhouse-grown transgenic trees on a dry-weight basis, but increased by 26–50% when calculated on a whole biomass basis in comparison to the wild-type control. Tendencies to increased glucose yields by up to 24% were present on a whole tree biomass basis after acidic pretreatment and enzymatic saccharification also in the transgenic trees grown for 5 years on the field when compared to the wild-type control.

    Conclusions: The results demonstrate the usefulness of gene-mining programs to identify novel genes with the potential to improve biofuel production in tree biotechnology programs. Furthermore, multi-omic analyses, including transcriptomic, proteomic and metabolomic analyses, performed here provide a toolbox for future studies on the function of VAP27 proteins in plants.

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  • 10. Hermansen, Russell A.
    et al.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1432 Ås, Norway.
    Sandve, Simen Rod
    Liberles, David A.
    Extracting functional trends from whole genome duplication events using comparative genomics2016In: Biological Procedures Online, E-ISSN 1480-9222, Vol. 18, article id 11Article, review/survey (Refereed)
    Abstract [en]

    Background: The number of species with completed genomes, including those with evidence for recent whole genome duplication events has exploded. The recently sequenced Atlantic salmon genome has been through two rounds of whole genome duplication since the divergence of teleost fish from the lineage that led to amniotes. This quadrupoling of the number of potential genes has led to complex patterns of retention and loss among gene families. Results: Methods have been developed to characterize the interplay of duplicate gene retention processes across both whole genome duplication events and additional smaller scale duplication events. Further, gene expression divergence data has become available as well for Atlantic salmon and the closely related, pre-whole genome duplication pike and methods to describe expression divergence are also presented. These methods for the characterization of duplicate gene retention and gene expression divergence that have been applied to salmon are described. Conclusions: With the growth in available genomic and functional data, the opportunities to extract functional inference from large scale duplicates using comparative methods have expanded dramatically. Recently developed methods that further this inference for duplicated genes have been described.

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  • 11.
    Hvidsten, Torgeir
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Kryshtafovych, Andriy
    Genome Center, UC Davis, Davis, California.
    Fidelis, Krzysztof
    Genome Center, UC Davis, Davis, California.
    Local descriptors of protein structure: a systematic analysis of the sequence-structure relationship in proteins using short- and long-range interactions.2009In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 75, no 4, p. 870-884Article in journal (Refereed)
    Abstract [en]

    Local protein structure representations that incorporate long-range contacts between residues are often considered in protein structure comparison but have found relatively little use in structure prediction where assembly from single backbone fragments dominates. Here, we introduce the concept of local descriptors of protein structure to characterize local neighborhoods of amino acids including short- and long-range interactions. We build a library of recurring local descriptors and show that this library is general enough to allow assembly of unseen protein structures. The library could on average re-assemble 83% of 119 unseen structures, and showed little or no performance decrease between homologous targets and targets with folds not represented among domains used to build it. We then systematically evaluate the descriptor library to establish the level of the sequence signal in sets of protein fragments of similar geometrical conformation. In particular, we test whether that signal is strong enough to facilitate correct assignment and alignment of these local geometries to new sequences. We use the signal to assign descriptors to a test set of 479 sequences with less than 40% sequence identity to any domain used to build the library, and show that on average more than 50% of the backbone fragments constituting descriptors can be correctly aligned. We also use the assigned descriptors to infer SCOP folds, and show that correct predictions can be made in many of the 151 cases where PSI-BLAST was unable to detect significant sequence similarity to proteins in the library. Although the combinatorial problem of simultaneously aligning several fragments to sequence is a major bottleneck compared with single fragment methods, the advantage of the current approach is that correct alignments imply correct long range distance constraints. The lack of these constraints is most likely the major reason why structure prediction methods fail to consistently produce adequate models when good templates are unavailable or undetectable. Thus, we believe that the current study offers new and valuable insight into the prediction of sequence-structure relationships in proteins.

  • 12.
    Hvidsten, Torgeir
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Laegreid, Astrid
    Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, St. Olavs Hospital HF, Trondheim, Norway.
    Kryshtafovych, Andriy
    UC Davis Genome Center, Davis, California, United States of America.
    Andersson, Gunnar
    The Linnaeus Centre for Bioinformatics, Uppsala University and The Swedish University for Agricultural Sciences, Uppsala, Sweden.
    Fidelis, Krzysztof
    UC Davis Genome Center, Davis, California, United States of America.
    Komorowski, Jan
    The Linnaeus Centre for Bioinformatics, Uppsala University and The Swedish University for Agricultural Sciences, Uppsala, Sweden.
    A comprehensive analysis of the structure-function relationship in proteins based on local structure similarity2009In: PLOS ONE, E-ISSN 1932-6203, Vol. 4, no 7, p. e6266-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sequence similarity to characterized proteins provides testable functional hypotheses for less than 50% of the proteins identified by genome sequencing projects. With structural genomics it is believed that structural similarities may give functional hypotheses for many of the remaining proteins. METHODOLOGY/PRINCIPAL FINDINGS: We provide a systematic analysis of the structure-function relationship in proteins using the novel concept of local descriptors of protein structure. A local descriptor is a small substructure of a protein which includes both short- and long-range interactions. We employ a library of commonly reoccurring local descriptors general enough to assemble most existing protein structures. We then model the relationship between these local shapes and Gene Ontology using rule-based learning. Our IF-THEN rule model offers legible, high resolution descriptions that combine local substructures and is able to discriminate functions even for functionally versatile folds such as the frequently occurring TIM barrel and Rossmann fold. By evaluating the predictive performance of the model, we provide a comprehensive quantification of the structure-function relationship based only on local structure similarity. Our findings are, among others, that conserved structure is a stronger prerequisite for enzymatic activity than for binding specificity, and that structure-based predictions complement sequence-based predictions. The model is capable of generating correct hypotheses, as confirmed by a literature study, even when no significant sequence similarity to characterized proteins exists. CONCLUSIONS/SIGNIFICANCE: Our approach offers a new and complete description and quantification of the structure-function relationship in proteins. By demonstrating how our predictions offer higher sensitivity than using global structure, and complement the use of sequence, we show that the presented ideas could advance the development of meta-servers in function prediction.

  • 13. Immanen, Juha
    et al.
    Nieminen, Kaisa
    Duchens Silva, Hector
    Rodriguez Rojas, Fernanda
    Meisel, Lee A.
    Silva, Herman
    Albert, Victor A.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Helariutta, Yka
    Characterization of cytokinin signaling and homeostasis gene families in two hardwood tree species: Populus trichocarpa and Prunus persica2013In: BMC Genomics, E-ISSN 1471-2164, Vol. 14, p. 885-Article in journal (Refereed)
    Abstract [en]

    Background: Through the diversity of cytokinin regulated processes, this phytohormone has a profound impact on plant growth and development. Cytokinin signaling is involved in the control of apical and lateral meristem activity, branching pattern of the shoot, and leaf senescence. These processes influence several traits, including the stem diameter, shoot architecture, and perennial life cycle, which define the development of woody plants. To facilitate research about the role of cytokinin in regulation of woody plant development, we have identified genes associated with cytokinin signaling and homeostasis pathways from two hardwood tree species. Results: Taking advantage of the sequenced black cottonwood (Populus trichocarpa) and peach (Prunus persica) genomes, we have compiled a comprehensive list of genes involved in these pathways. We identified genes belonging to the six families of cytokinin oxidases (CKXs), isopentenyl transferases (IPTs), LONELY GUY genes (LOGs), two-component receptors, histidine containing phosphotransmitters (HPts), and response regulators (RRs). All together 85 Populus and 45 Prunus genes were identified, and compared to their Arabidopsis orthologs through phylogenetic analyses. Conclusions: In general, when compared to Arabidopsis, differences in gene family structure were often seen in only one of the two tree species. However, one class of genes associated with cytokinin signal transduction, the CKI1-like family of two-component histidine kinases, was larger in both Populus and Prunus than in Arabidopsis.

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  • 14.
    Ingvarsson, Pär K.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1432,As, Norway.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Towards integration of population and comparative genomics in forest trees2016In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 212, no 2, p. 338-344Article, review/survey (Refereed)
    Abstract [en]

    The past decade saw the initiation of an ongoing revolution in sequencing technologies that is transforming all fields of biology. This has been driven by the advent and widespread availability of high-throughput, massively parallel short-read sequencing (MPS) platforms. These technologies have enabled previously unimaginable studies, including draft assemblies of the massive genomes of coniferous species and population-scale resequencing. Transcriptomics studies have likewise been transformed, with RNA-sequencing enabling studies in nonmodel organisms, the discovery of previously unannotated genes (novel transcripts), entirely new classes of RNAs and previously unknown regulatory mechanisms. Here we touch upon current developments in the areas of genome assembly, comparative regulomics and population genetics as they relate to studies of forest tree species.

  • 15.
    Jokipii-Lukkari, Soile
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology,Swedish University of Agricultural Sciences, SE-901 84 Umeå, Sweden.
    Sundell, David
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Nilsson, Ove
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1430 Ås, Norway.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    NorWood: a gene expression resource for evo-devo studies of conifer wood development2017In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 216, no 2, p. 482-494Article in journal (Refereed)
    Abstract [en]

    The secondary xylem of conifers is composed mainly of tracheids that differ anatomically and chemically from angiosperm xylem cells. There is currently no high-spatial-resolution data available profiling gene expression during wood formation for any coniferous species, which limits insight into tracheid development.

    RNA-sequencing data from replicated, high-spatial-resolution section series throughout the cambial and woody tissues of Picea abies were used to generate the NorWood.conGenIE.org web resource, which facilitates exploration of the associated gene expression profiles and co-expression networks.

    Integration within PlantGenIE.org enabled a comparative regulomics analysis, revealing divergent co-expression networks between P. abies and the two angiosperm species Arabidopsis thaliana and Populus tremula for the secondary cell wall (SCW) master regulator NAC Class IIB transcription factors. The SCW cellulose synthase genes (CesAs) were located in the neighbourhoods of the NAC factors in Athaliana and P. tremula, but not in Pabies. The NorWood co-expression network enabled identification of potential SCW CesA regulators in P. abies.

    The NorWood web resource represents a powerful community tool for generating evo-devo insights into the divergence of wood formation between angiosperms and gymnosperms and for advancing understanding of the regulation of wood development in P. abies.

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  • 16. Lien, Sigbjorn
    et al.
    Koop, Ben F.
    Sandve, Simen R.
    Miller, Jason R.
    Kent, Matthew P.
    Nome, Torfinn
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Leong, Jong S.
    Minkley, David R.
    Zimin, Aleksey
    Grammes, Fabian
    Grove, Harald
    Gjuvsland, Arne
    Walenz, Brian
    Hermansen, Russell A.
    von Schalburg, Kris
    Rondeau, Eric B.
    Di Genova, Alex
    Samy, Jeevan K. A.
    Vik, Jon Olav
    Vigeland, Magnus D.
    Caler, Lis
    Grimholt, Unni
    Jentoft, Sissel
    Vage, Dag Inge
    de Jong, Pieter
    Moen, Thomas
    Baranski, Matthew
    Palti, Yniv
    Smith, Douglas R.
    Yorke, James A.
    Nederbragt, Alexander J.
    Tooming-Klunderud, Ave
    Jakobsen, Kjetill S.
    Jiang, Xuanting
    Fan, Dingding
    Liberles, David A.
    Vidal, Rodrigo
    Iturra, Patricia
    Jones, Steven J. M.
    Jonassen, Inge
    Maass, Alejandro
    Omholt, Stig W.
    Davidson, William S.
    The Atlantic salmon genome provides insights into rediploidization2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 533, no 7602, p. 200-205Article in journal (Refereed)
    Abstract [en]

    The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.

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  • 17. Lin, Yao-Cheng
    et al.
    Wang, Jing
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, Ås, Norway.
    Delhomme, Nicolas
    Schiffthaler, Bastian
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Sundström, Görel
    Zuccolo, Andrea
    Nystedt, Björn
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    de la Torre, Amanda
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). School of Forestry, Northern Arizona University, Flagstaff, AZ.
    Cossu, Rosa M.
    Hoeppner, Marc P.
    Lantz, Henrik
    Scofield, Douglas G.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Ecology and Genetics: Evolutionary Biology, Uppsala University, Sweden; Uppsala Multidisciplinary Center for Advanced Computational Science, Uppsala University, Sweden.
    Zamani, Neda
    Johansson, Anna
    Mannapperuma, Chanaka
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Robinson, Kathryn M.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Mähler, Niklas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Leitch, Ilia J.
    Pellicer, Jaume
    Park, Eung-Jun
    Van Montagu, Marc
    Van de Peer, Yves
    Grabherr, Manfred
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Plant Biology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 46, p. E10970-E10978Article in journal (Refereed)
    Abstract [en]

    The Populus genus is one of the major plant model systems, but genomic resources have thus far primarily been available for poplar species, and primarily Populus trichocarpa (Torr. & Gray), which was the first tree with a whole-genome assembly. To further advance evolutionary and functional genomic analyses in Populus, we produced genome assemblies and population genetics resources of two aspen species, Populus tremula L. and Populus tremuloides Michx. The two aspen species have distributions spanning the Northern Hemisphere, where they are keystone species supporting a wide variety of dependent communities and produce a diverse array of secondary metabolites. Our analyses show that the two aspens share a similar genome structure and a highly conserved gene content with P. trichocarpa but display substantially higher levels of heterozygosity. Based on population resequencing data, we observed widespread positive and negative selection acting on both coding and noncoding regions. Furthermore, patterns of genetic diversity and molecular evolution in aspen are influenced by a number of features, such as expression level, coexpression network connectivity, and regulatory variation. To maximize the community utility of these resources, we have integrated all presented data within the PopGenIE web resource (PopGenIE.org).

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  • 18.
    Mannapperuma, Chanaka
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Liu, H.
    Bel, M.
    Delhomme, Nicolas
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Serrano, A.
    Schiffthaler, Bastian
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Vandepoele, K.
    Ayllón-Benítez, A.
    Street, Nathaniel
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    PlantGenIE-PLAZA: integrating orthology into the PlantGenIE.org resource using the PLAZA pipeline2020Manuscript (preprint) (Other academic)
  • 19.
    Miranda, Helder
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Charegi, Otilia
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Netotea, Sergiu
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hvidsten, Torgeir R
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    Funk, Christiane
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Co-expression analysis, proteomic and metabolomic study on the impact of a Deg/HtrA protease triple mutant in Synechocystis sp. PCC 6803 exposed to temperature and high light stress2013In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 78, p. 294-311Article in journal (Refereed)
    Abstract [en]

    Members of the DegP/HtrA protease family are widespread in nature and play an important role in proteolysis of misfolded and damaged proteins. The cyanobacterium Synechocystis sp. PCC 6803 contains three Deg proteases, HhoA (Sll1679), HhoB (Sll1427) and HtrA (Slr1204). Using the proteomic or metabolomic approach we investigated a triple deletion mutant (Δdeg) exposed to light or temperature stress. To cope with the stress conditions the triple mutant reduces its energy metabolism and stress-related proteins are induced to protect the cells. Additionally the co-expression of the genes encoding the three proteases with other genes in Synechocystis sp. PCC 6803 was analyzed. While HhoA seems to be involved in house-keeping processes related to protein (re)folding, protein clearance and signaling, the hhoB expression cluster is dominated by genes encoding periplasmic proteins linked to metabolism or signal transduction pathways. The htrA expression pattern is similar to that of genes encoding proteins of the electron transport chain, iron- and nitrogen metabolism. Our integrative approach indicates significant rearrangements in cells depleted of the Deg/HtrA proteases when exposed to stress, both, in the cytoplasmic and extracytoplasmic space.

  • 20.
    Mähler, Niklas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Norwegian Univ Life Sci, Dept Chem Biotechnol & Food Sci, Norway.
    Wang, Jing
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Centre for Integrative Genetics, Faculty of Biosciences, Norwegian University of Life Sciences, Norway.
    Terebieniec, Barbara K.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Swedish Univ Agr Sci, Dept Plant Biol, Uppsala, Sweden.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Norwegian Univ Life Sci, Dept Chem Biotechnol & Food Sci, As, Norway.
    Gene co-expression network connectivity is an important determinant of selective constraint2017In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 4, article id e1006402Article in journal (Refereed)
    Abstract [en]

    While several studies have investigated general properties of the genetic architecture of natural variation in gene expression, few of these have considered natural, outbreeding populations. In parallel, systems biology has established that a general feature of biological networks is that they are scale-free, rendering them buffered against random mutations. To date, few studies have attempted to examine the relationship between the selective processes acting to maintain natural variation of gene expression and the associated co-expression network structure. Here we utilised RNA-Sequencing to assay gene expression in winter buds undergoing bud flush in a natural population of Populus tremula, an outbreeding forest tree species. We performed expression Quantitative Trait Locus (eQTL) mapping and identified 164,290 significant eQTLs associating 6,241 unique genes (eGenes) with 147,419 unique SNPs (eSNPs). We found approximately four times as many local as distant eQTLs, with local eQTLs having significantly higher effect sizes. eQTLs were primarily located in regulatory regions of genes (UTRs or flanking regions), regardless of whether they were local or distant. We used the gene expression data to infer a co-expression network and investigated the relationship between network topology, the genetic architecture of gene expression and signatures of selection. Within the co-expression network, eGenes were underrepresented in network module cores (hubs) and overrepresented in the periphery of the network, with a negative correlation between eQTL effect size and network connectivity. We additionally found that module core genes have experienced stronger selective constraint on coding and non-coding sequence, with connectivity associated with signatures of selection. Our integrated genetics and genomics results suggest that purifying selection is the primary mechanism underlying the genetic architecture of natural variation in gene expression assayed in flushing leaf buds of P. tremula and that connectivity within the co-expression network is linked to the strength of purifying selection.

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  • 21.
    Netotea, Sergiu
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Sundell, David
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    ComPlEx: conservation and divergence of co-expression networks in A. thaliana, Populus and O. sativa2014In: BMC Genomics, E-ISSN 1471-2164, Vol. 15, p. 106-Article in journal (Refereed)
    Abstract [en]

    Background: Divergence in gene regulation has emerged as a key mechanism underlying species differentiation. Comparative analysis of co-expression networks across species can reveal conservation and divergence in the regulation of genes. Results: We inferred co-expression networks of A. thaliana, Populus spp. and O. sativa using state-of-the-art methods based on mutual information and context likelihood of relatedness, and conducted a comprehensive comparison of these networks across a range of co-expression thresholds. In addition to quantifying gene-gene link and network neighbourhood conservation, we also applied recent advancements in network analysis to do cross-species comparisons of network properties such as scale free characteristics and gene centrality as well as network motifs. We found that in all species the networks emerged as scale free only above a certain co-expression threshold, and that the high-centrality genes upholding this organization tended to be conserved. Network motifs, in particular the feed-forward loop, were found to be significantly enriched in specific functional subnetworks but where much less conserved across species than gene centrality. Although individual gene-gene co-expression had massively diverged, up to similar to 80% of the genes still had a significantly conserved network neighbourhood. For genes with multiple predicted orthologs, about half had one ortholog with conserved regulation and another ortholog with diverged or non-conserved regulation. Furthermore, the most sequence similar ortholog was not the one with the most conserved gene regulation in over half of the cases. Conclusions: We have provided a comprehensive analysis of gene regulation evolution in plants and built a web tool for Comparative analysis of Plant co-Expression networks (ComPlEx, http:// complex. plantgenie. org/). The tool can be particularly useful for identifying the ortholog with the most conserved regulation among several sequence-similar alternatives and can thus be of practical importance in e. g. finding candidate genes for perturbation experiments.

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  • 22. Nystedt, Björn
    et al.
    Street, Nathaniel Robert
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Wetterbom, Anna
    Zuccolo, Andrea
    Lin, Yao-Cheng
    Scofield, Douglas G.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Vezzi, Francesco
    Delhomme, Nicolas
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Giacomello, Stefania
    Alexeyenko, Andrey
    Vicedomini, Riccardo
    Sahlin, Kristoffer
    Sherwood, Ellen
    Elfstrand, Malin
    Gramzow, Lydia
    Holmberg, Kristina
    Hällman, Jimmie
    Keech, Olivier
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Klasson, Lisa
    Koriabine, Maxim
    Kucukoglu, Melis
    Käller, Max
    Luthman, Johannes
    Lysholm, Fredrik
    Niittylä, Totte
    Olson, Åke
    Rilakovic, Nemanja
    Ritland, Carol
    Rosselló, Josep A.
    Sena, Juliana
    Svensson, Thomas
    Talavera-López, Carlos
    Theißen, Günter
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Vanneste, Kevin
    Wu, Zhi-Qiang
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Zhang, Bo
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Zerbe, Philipp
    Arvestad, Lars
    Bhalerao, Rishikesh
    Bohlmann, Joerg
    Bousquet, Jean
    Gil, Rosario Garcia
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    de Jong, Pieter
    MacKay, John
    Morgante, Michele
    Ritland, Kermit
    Sundberg, Björn
    Thompson, Stacey Lee
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Van de Peer, Yves
    Andersson, Björn
    Nilsson, Ove
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lundeberg, Joakim
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    The Norway spruce genome sequence and conifer genome evolution2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 497, no 7451, p. 579-584Article in journal (Refereed)
    Abstract [en]

    Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

  • 23.
    Obudulu, Ogonna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bygdell, Joakim
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sundberg, Bjorn
    Moritz, Thomas
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. 5 Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Norway.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wingsle, Gunnar
    Quantitative proteomics reveals protein profiles underlying major transitions in aspen wood development2016In: BMC Genomics, E-ISSN 1471-2164, Vol. 17, article id 119Article in journal (Refereed)
    Abstract [en]

    Background: Wood development is of outstanding interest both to basic research and industry due to the associated cellulose and lignin biomass production. Efforts to elucidate wood formation (which is essential for numerous aspects of both pure and applied plant science) have been made using transcriptomic analyses and/or low-resolution sampling. However, transcriptomic data do not correlate perfectly with levels of expressed proteins due to effects of post-translational modifications and variations in turnover rates. In addition, high-resolution analysis is needed to characterize key transitions. In order to identify protein profiles across the developmental region of wood formation, an in-depth and tissue specific sampling was performed. Results: We examined protein profiles, using an ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry system, in high-resolution tangential sections spanning all wood development zones in Populus tremula from undifferentiated cambium to mature phloem and xylem, including cell expansion and cell death zones. In total, we analyzed 482 sections, 20-160 mu m thick, from four 47-year-old trees growing wild in Sweden. We obtained high quality expression profiles for 3,082 proteins exhibiting consistency across the replicates, considering that the trees were growing in an uncontrolled environment. A combination of Principal Component Analysis (PCA), Orthogonal Projections to Latent Structures (OPLS) modeling and an enhanced stepwise linear modeling approach identified several major transitions in global protein expression profiles, pinpointing (for example) locations of the cambial division leading to phloem and xylem cells, and secondary cell wall formation zones. We also identified key proteins and associated pathways underlying these developmental landmarks. For example, many of the lignocellulosic related proteins were upregulated in the expansion to the early developmental xylem zone, and for laccases with a rapid decrease in early xylem zones. We observed upregulation of two forms of xylem cysteine protease (Potri.002G005700.1 and Potri.005G256000.2; Pt-XCP2.1) in early xylem and their downregulation in late maturing xylem. Our data also show that Pt-KOR1.3 (Potri.003G151700.2) exhibits an expression pattern that supports the hypothesis put forward in previous studies that this is a key xyloglucanase involved in cellulose biosynthesis in primary cell walls and reduction of cellulose crystallinity in secondary walls. Conclusion: Our novel multivariate approach highlights important processes and provides confirmatory insights into the molecular foundations of wood development.

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  • 24.
    Obudulu, Ogonna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, 90183 Umeå, Sweden.
    Mähler, Niklas
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Faculty of Chemistry, Biotechnology and Food Science, Norwegian, University of Life Sciences, 1432 Ås, Norway.
    Skotare, Tomas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bygdell, Joakim
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Abreu, Ilka N.
    Ahnlund, Maria
    Latha Gandla, Madhavi
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Petterle, Anna
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Moritz, Thomas
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Faculty of Chemistry, Biotechnology and Food Science, Norwegian, University of Life Sciences, 1432 Ås, Norway.
    Jönsson, Leif J.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wingsle, Gunnar
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees2018In: BMC Genomics, E-ISSN 1471-2164, Vol. 19, article id 11Article in journal (Refereed)
    Abstract [en]

    Background: Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32–38 kDa proteins that are involved in membrane trafficking. A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees. Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3;Potri.019G104000).

    Results: The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls. This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines. Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition. The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type. Several of these were related to secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis.

    Conclusions: Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems. Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport. The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.

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  • 25. Robertson, Fiona M.
    et al.
    Gundappa, Manu Kumar
    Grammes, Fabian
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Redmond, Anthony K.
    Lien, Sigbjørn
    Martin, Samuel A. M.
    Holland, Peter W. H.
    Sandve, Simen R.
    Macqueen, Daniel J.
    Lineage-specific rediploidization is a mechanism to explain time-lags between genome duplication and evolutionary diversification2017In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 18, article id 111Article in journal (Refereed)
    Abstract [en]

    Background: The functional divergence of duplicate genes (ohnologues) retained from whole genome duplication (WGD) is thought to promote evolutionary diversification. However, species radiation and phenotypic diversification are often temporally separated from WGD. Salmonid fish, whose ancestor underwent WGD by autotetraploidization similar to 95 million years ago, fit such a 'time-lag' model of post-WGD radiation, which occurred alongside a major delay in the rediploidization process. Here we propose a model, 'lineage-specific ohnologue resolution' (LORe), to address the consequences of delayed rediploidization. Under LORe, speciation precedes rediploidization, allowing independent ohnologue divergence in sister lineages sharing an ancestral WGD event. Results: Using cross-species sequence capture, phylogenomics and genome-wide analyses of ohnologue expression divergence, we demonstrate the major impact of LORe on salmonid evolution. One-quarter of each salmonid genome, harbouring at least 4550 ohnologues, has evolved under LORe, with rediploidization and functional divergence occurring on multiple independent occasions >50 million years post-WGD. We demonstrate the existence and regulatory divergence of many LORe ohnologues with functions in lineage-specific physiological adaptations that potentially facilitated salmonid species radiation. We show that LORe ohnologues are enriched for different functions than 'older' ohnologues that began diverging in the salmonid ancestor. Conclusions: LORe has unappreciated significance as a nested component of post-WGD divergence that impacts the functional properties of genes, whilst providing ohnologues available solely for lineage-specific adaptation. Under LORe, which is predicted following many WGD events, the functional outcomes of WGD need not appear 'explosively', but can arise gradually over tens of millions of years, promoting lineage-specific diversification regimes under prevailing ecological pressures.

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  • 26.
    Robinson, Kathryn
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Delhomme, Nicolas
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Mahler, Niklas
    Schiffthaler, Bastian
    Önskog, Jenny
    Albrectsen, Benedicte
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Ingvarsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Street, Nathaniel
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Populus tremula (European aspen) shows no evidence of sexual dimorphism2014In: BMC Plant Biology, E-ISSN 1471-2229, Vol. 14, p. 276-Article in journal (Refereed)
    Abstract [en]

    Background:

    Evolutionary theory suggests that males and females may evolve sexually dimorphic phenotypic and biochemical traits concordant with each sex having different optimal strategies of resource investment to maximise reproductive success and fitness. Such sexual dimorphism would result in sex biased gene expression patterns in non-floral organs for autosomal genes associated with the control and development of such phenotypic traits.

    Results:

    We examined morphological, biochemical and herbivory traits to test for sexually dimorphic resource allocation strategies within collections of sexually mature and immature Populus tremula (European aspen) trees. In addition we profiled gene expression in mature leaves of sexually mature wild trees using whole-genome oligonucleotide microarrays and RNA-Sequencing.

    Conclusions:

    We found no evidence of sexual dimorphism or differential resource investment strategies between males and females in either sexually immature or mature trees. Similarly, single-gene differential expression and machine learning approaches revealed no evidence of large-scale sex biased gene expression. However, two significantly differentially expressed genes were identified from the RNA-Seq data, one of which is a robust diagnostic marker of sex in P. tremula.

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  • 27. Sandve, Simen R.
    et al.
    Rohlfs, Rori V.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Subfunctionalization versus neofunctionalization after whole-genome duplication2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 7, p. 908-909Article in journal (Refereed)
  • 28. Schubert, Marian
    et al.
    Gronvold, Lars
    Sandve, Simen R.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Fjellheim, Siri
    Evolution of Cold Acclimation and Its Role in Niche Transition in the Temperate Grass Subfamily Pooideae2019In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 180, no 1, p. 404-419Article in journal (Refereed)
    Abstract [en]

    The grass subfamily Pooideae dominates the grass floras in cold temperate regions and has evolved complex physiological adaptations to cope with extreme environmental conditions like frost, winter, and seasonality. One such adaptation is cold acclimation, wherein plants increase their frost tolerance in response to gradually falling temperatures and shorter days in the autumn. However, understanding how complex traits like cold acclimation evolve remains a major challenge in evolutionary biology. Here, we investigated the evolution of cold acclimation in Pooideae and found that a phylogenetically diverse set of Pooideae species displayed cold acclimation capacity. However, comparing differential gene expression after cold treatment in transcriptomes of five phylogenetically diverse species revealed widespread species-specific responses of genes with conserved sequences. Furthermore, we studied the correlation between gene family size and number of cold-responsive genes as well as between selection pressure on coding sequences of genes and their cold responsiveness. We saw evidence of protein-coding and regulatory sequence evolution as well as the origin of novel genes and functions contributing toward evolution of a cold response in Pooideae. Our results reflect that selection pressure resulting from global cooling must have acted on already diverged lineages. Nevertheless, conservation of cold-induced gene expression of certain genes indicates that the Pooideae ancestor may have possessed some molecular machinery to mitigate cold stress. Evolution of adaptations to seasonally cold climates is regarded as particularly difficult. How Pooideae evolved to transition from tropical to temperate biomes sheds light on how complex traits evolve in the light of climate changes.

  • 29.
    Seyfferth, Carolin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Wessels, Bernard
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Vahala, Jorma
    Kangasjärvi, Jaakko
    Delhomme, Nicolas
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Tuominen, Hannele
    Lundberg-Felten, Judith
    PopulusPtERF85 Balances Xylem Cell Expansion and Secondary Cell Wall Formation in Hybrid Aspen2021In: Cells, E-ISSN 2073-4409, Vol. 10, no 8, article id 1971Article in journal (Refereed)
    Abstract [en]

    Secondary growth relies on precise and specialized transcriptional networks that determine cell division, differentiation, and maturation of xylem cells. We identified a novel role for the ethylene-induced Populus Ethylene Response Factor PtERF85 (Potri.015G023200) in balancing xylem cell expansion and secondary cell wall (SCW) formation in hybrid aspen (Populus tremula x tremuloides). Expression of PtERF85 is high in phloem and cambium cells and during the expansion of xylem cells, while it is low in maturing xylem tissue. Extending PtERF85 expression into SCW forming zones of woody tissues through ectopic expression reduced wood density and SCW thickness of xylem fibers but increased fiber diameter. Xylem transcriptomes from the transgenic trees revealed transcriptional induction of genes involved in cell expansion, translation, and growth. The expression of genes associated with plant vascular development and the biosynthesis of SCW chemical components such as xylan and lignin, was down-regulated in the transgenic trees. Our results suggest that PtERF85 activates genes related to xylem cell expansion, while preventing transcriptional activation of genes related to SCW formation. The importance of precise spatial expression of PtERF85 during wood development together with the observed phenotypes in response to ectopic PtERF85 expression suggests that PtERF85 contributes to the transition of fiber cells from elongation to secondary cell wall deposition.

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  • 30. Srivastava, Vaibhav
    et al.
    Obudulu, Ogonna
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University and Swedish University of Agricultural Sciences.
    Bygdell, Joakim
    Löfstedt, Tommy
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University.
    Nilsson, Robert
    Ahnlund, Maria
    Johansson, Annika
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University.
    Freyhult, Eva
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Computational life science cluster (CLiC), Umeå University.
    Qvarnström, Johanna
    Karlsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Melzer, Michael
    Moritz, Thomas
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University.
    Hvidsten, Torgeir R
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational life science cluster (CLiC), Umeå University and Department of Chemistry, Biotechnology; Food Science, Norwegian, University of Life Sciences, Ås Norwegian, Norway.
    Wingsle, Gunnar
    OnPLS integration of transcriptomic, proteomic and metabolomic data shows multi-level oxidative stress responses in the cambium of transgenic hipI- superoxide dismutase Populus plants2013In: BMC Genomics, E-ISSN 1471-2164, Vol. 14, article id 893Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Reactive oxygen species (ROS) are involved in the regulation of diverse physiological processes in plants, including various biotic and abiotic stress responses. Thus, oxidative stress tolerance mechanisms in plants are complex, and diverse responses at multiple levels need to be characterized in order to understand them. Here we present system responses to oxidative stress in Populus by integrating data from analyses of the cambial region of wild-type controls and plants expressing high-isoelectric-point superoxide dismutase (hipI-SOD) transcripts in antisense orientation showing a higher production of superoxide. The cambium, a thin cell layer, generates cells that differentiate to form either phloem or xylem and is hypothesized to be a major reason for phenotypic perturbations in the transgenic plants. Data from multiple platforms including transcriptomics (microarray analysis), proteomics (UPLC/QTOF-MS), and metabolomics (GC-TOF/MS, UPLC/MS, and UHPLC-LTQ/MS) were integrated using the most recent development of orthogonal projections to latent structures called OnPLS. OnPLS is a symmetrical multi-block method that does not depend on the order of analysis when more than two blocks are analysed. Significantly affected genes, proteins and metabolites were then visualized in painted pathway diagrams.

    RESULTS: The main categories that appear to be significantly influenced in the transgenic plants were pathways related to redox regulation, carbon metabolism and protein degradation, e.g. the glycolysis and pentose phosphate pathways (PPP). The results provide system-level information on ROS metabolism and responses to oxidative stress, and indicate that some initial responses to oxidative stress may share common pathways.

    CONCLUSION: The proposed data evaluation strategy shows an efficient way of compiling complex, multi-platform datasets to obtain significant biological information.

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  • 31.
    Street, Nathaniel Robert
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    A systems biology model of the regulatory network in Populus leaves reveals interacting regulators and conserved regulation2011In: BMC Plant Biology, E-ISSN 1471-2229, Vol. 11, p. 13-Article in journal (Refereed)
    Abstract [en]

    We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions can provide hypotheses about the underlying cause of emergent properties and are needed if we are to identify target genes other than those constituting the "low hanging fruit" of genomic analysis.

  • 32. Strombergsson, Helena
    et al.
    Daniluk, Pawel
    Kryshtafovych, Andriy
    Fidelis, Krzysztof
    Wikberg, Jarl
    Kleywegt, Gerard
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Interaction Model Based on Local Protein Substructures Generalizes to the Entire Structural Enzyme-Ligand Space.2008In: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 48, p. 2278-2288Article in journal (Refereed)
    Abstract [en]

    Chemogenomics is a new strategy in in silico drug discovery, where the ultimate goal is to understand molecular recognition for all molecules interacting with all proteins in the proteome. To study such cross interactions, methods that can generalize over proteins that vary greatly in sequence, structure, and function are needed. We present a general quantitative approach to protein−ligand binding affinity prediction that spans the entire structural enzyme-ligand space. The model was trained on a data set composed of all available enzymes cocrystallized with druglike ligands, taken from four publicly available interaction databases, for which a crystal structure is available. Each enzyme was characterized by a set of local descriptors of protein structure that describe the binding site of the cocrystallized ligand. The ligands in the training set were described by traditional QSAR descriptors. To evaluate the model, a comprehensive test set consisting of enzyme structures and ligands was manually curated. The test set contained enzyme-ligand complexes for which no crystal structures were available, and thus the binding modes were unknown. The test set enzymes were therefore characterized by matching their entire structures to the local descriptor library constructed from the training set. Both the training and the test set contained enzyme-ligand complexes from all major enzyme classes, and the enzymes spanned a large range of sequences and folds. The experimental binding affinities (pKi) ranged from 0.5 to 11.9 (0.7−11.0 in the test set). The induced model predicted the binding affinities of the external test set enzyme-ligand complexes with an r2 of 0.53 and an RMSEP of 1.5. This demonstrates that the use of local descriptors makes it possible to create rough predictive models that can generalize over a wide range of protein targets.

  • 33.
    Sundell, David
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mannapperuma, Chanaka
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Netotea, Sergiu
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Delhomme, Nicolas
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Lin, Yao-Cheng
    Sjödin, Andreas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Van de Peer, Yves
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Chemistry,Biotechnology and Food Science, Norwegi an University of Life Sciences, 1432As, Norw.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Department of Chemistry.
    The Plant Genome Integrative Explorer Resource: PlantGenIE.org2015In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 208, no 4, p. 1149-1156Article in journal (Refereed)
    Abstract [en]

    Accessing and exploring large-scale genomics data sets remains a significant challenge to researchers without specialist bioinformatics training. We present the integrated PlantGenIE.org platform for exploration of Populus, conifer and Arabidopsis genomics data, which includes expression networks and associated visualization tools. Standard features of a model organism database are provided, including genome browsers, gene list annotation, BLAST homology searches and gene information pages. Community annotation updating is supported via integration of WebApollo. We have produced an RNA-sequencing (RNA-Seq) expression atlas for Populus tremula and have integrated these data within the expression tools. An updated version of the COMPLEX resource for performing comparative plant expression analyses of gene coexpression network conservation between species has also been integrated. The PlantGenIE.org platform provides intuitive access to large-scale and genome-wide genomics data from model forest tree species, facilitating both community contributions to annotation improvement and tools supporting use of the included data resources to inform biological insight.

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  • 34.
    Sundell, David
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Kumar, Manoj
    Mellerowicz, Ewa J.
    Kucukoglu, Melis
    Johnsson, Christoffer
    Kumar, Vikash
    Mannapperuma, Chanaka
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Delhomme, Nicolas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Nilsson, Ove
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Pesquet, Edouard
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Ecology, Environment and Plant Sciences, Stockholm University, 106 91 Stockholm, Sweden.
    Fischer, Urs
    Niittyla, Totte
    Sundberg, Bjorn
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, 1433 Ås, Norway.
    AspWood: High-Spatial-Resolution Transcriptome Profiles Reveal Uncharacterized Modularity of Wood Formation in Populus tremula2017In: The Plant Cell, ISSN 1040-4651, E-ISSN 1532-298X, Vol. 29, no 7, p. 1585-1604Article in journal (Refereed)
    Abstract [en]

    Trees represent the largest terrestrial carbon sink and a renewable source of ligno-cellulose. There is significant scope for yield and quality improvement in these largely undomesticated species, and efforts to engineer elite varieties will benefit from improved understanding of the transcriptional network underlying cambial growth and wood formation. We generated high-spatial-resolution RNA sequencing data spanning the secondary phloem, vascular cambium, and wood-forming tissues of Populus tremula. The transcriptome comprised 28,294 expressed, annotated genes, 78 novel protein-coding genes, and 567 putative long intergenic noncoding RNAs. Most paralogs originating from the Salicaceae whole-genome duplication had diverged expression, with the exception of those highly expressed during secondary cell wall deposition. Coexpression network analyses revealed that regulation of the transcriptome underlying cambial growth and wood formation comprises numerous modules forming a continuum of active processes across the tissues. A comparative analysis revealed that a majority of these modules are conserved in Picea abies. The high spatial resolution of our data enabled identification of novel roles for characterized genes involved in xylan and cellulose biosynthesis, regulators of xylem vessel and fiber differentiation and lignification. An associated web resource (AspWood, http://aspwood.popgenie.org) provides interactive tools for exploring the expression profiles and coexpression network.

  • 35.
    Sundell, David
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Street, Nathaniel R
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Kumar, Manoj
    Mellerowicz, Ewa J
    Kucukoglu, Melis
    Johnsson, Christoffer
    Kumar, Vikash
    Mannapperuma, Chanaka
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Nilsson, Ove
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Pesquet, Edouard
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Ecology, Environment and Plant Sciences, Stockholm University, Sweden.
    Fischer, Urs
    Niittyla, Totte
    Sundberg, Bjoern
    Hvidsten, Torgeir R
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, Ås, Norway.
    High-spatial-resolution transcriptome profiling reveals uncharacterized regulatory complexity underlying cambial growth and wood formation in Populus tremula2016Manuscript (preprint) (Other academic)
    Abstract [en]

    Trees represent the largest terrestrial carbon sink and a renewable source of ligno-cellulose. There is significant scope for yield and quality improvement in these largely undomesticated species, however, efforts to engineer new, elite varieties are constrained by the lack of a comprehensive understanding of the transcriptional network underlying cambial growth and wood formation. We generated RNA Sequencing transcriptome data for four mature, wild-growing aspens (Populus tremula) from high-spatial-resolution tangential cryosection series spanning the secondary phloem, vascular cambium, expanding and secondary cell wall forming xylem cells, cell death zone and the previous years annual ring. The transcriptome comprised 28,294 expressed, previously annotated protein-coding genes, 78 novel protein-coding genes and 567 long intergenic non-coding RNAs. Most paralogs originating from the Salicaceae whole genome duplication had diverged expression, with the notable exception of those with high expression during secondary cell wall deposition. We performed co-expression network analysis to identify central transcriptional modules and associated several of these with known biological processes. This revealed previously uncharacterized complexity underlying the regulation of cambial growth and wood formation, with modules forming a continuum of activated processes across the tissues. The high spatial resolution suggested novel roles for known genes involved in xylan and cellulose biosynthesis, regulators of xylem vessel and fiber differentiation and components of lignification. The associated web resource (AspWood, http://aspwood.popgenie.org) integrates the data within a set of interactive tools for exploring the co-expression network of cambial growth and wood formation.

  • 36. Tylewicz, S.
    et al.
    Petterle, A.
    Marttila, S.
    Miskolczi, P.
    Azeez, A.
    Singh, R. K.
    Immanen, J.
    Mähler, Niklas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Hvidsten, Torgerir R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
    Eklund, D. M.
    Bowman, J. L.
    Helariutta, Y.
    Bhalerao, R. P.
    Photoperiodic control of seasonal growth is mediated by ABA acting on cell-cell communication2018In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 360, no 6385, p. 212-214Article in journal (Refereed)
    Abstract [en]

    In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic intercellular communication through plasmodesmata is blocked by a process dependent on the phytohormone abscisic acid. The communication blockage prevents growth-promoting signals from accessing the meristem. Thus, precocious growth is disallowed during dormancy. The dormant period, which supports robust survival of the aspen tree in winter, is due to loss of access to growth-promoting signals.

  • 37. Varadharajan, Srinidhi
    et al.
    Sandve, Simen R.
    Gillard, Gareth B.
    Tørresen, Ole K.
    Mulugeta, Teshome D.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lien, Sigbjørn
    Vøllestad, Leif Asbjørn
    Jentoft, Sissel
    Nederbragt, Alexander J.
    Jakobsen, Kjetill S.
    The Grayling Genome Reveals Selection on Gene Expression Regulation after Whole-Genome Duplication2018In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 10, no 10, p. 2785-2800Article in journal (Refereed)
    Abstract [en]

    Whole-genome duplication (WGD) has been a major evolutionary driver of increased genomic complexity in vertebrates. One such event occurred in the salmonid family ∼80 Ma (Ss4R) giving rise to a plethora of structural and regulatory duplicate-driven divergence, making salmonids an exemplary system to investigate the evolutionary consequences of WGD. Here, we present a draft genome assembly of European grayling (Thymallus thymallus) and use this in a comparative framework to study evolution of gene regulation following WGD. Among the Ss4R duplicates identified in European grayling and Atlantic salmon (Salmo salar), one-third reflect nonneutral tissue expression evolution, with strong purifying selection, maintained over ∼50 Myr. Of these, the majority reflect conserved tissue regulation under strong selective constraints related to brain and neural-related functions, as well as higher-order protein–protein interactions. A small subset of the duplicates have evolved tissue regulatory expression divergence in a common ancestor, which have been subsequently conserved in both lineages, suggestive of adaptive divergence following WGD. These candidates for adaptive tissue expression divergence have elevated rates of protein coding- and promoter-sequence evolution and are enriched for immune- and lipid metabolism ontology terms. Lastly, lineage-specific duplicate divergence points toward underlying differences in adaptive pressures on expression regulation in the nonanadromous grayling versus the anadromous Atlantic salmon. Our findings enhance our understanding of the role of WGD in genome evolution and highlight cases of regulatory divergence of Ss4R duplicates, possibly related to a niche shift in early salmonid evolution.

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  • 38. Wabnik, Krzysztof
    et al.
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Kedzierska, Anna
    Van Leene, Jelle
    De Jaeger, Geert
    Beemster, Gerrit T S
    Komorowski, Jan
    Kuiper, Martin T R
    Gene expression trends and protein features effectively complement each other in gene function prediction2009In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 25, no 3, p. 322-330Article in journal (Refereed)
    Abstract [en]

    MOTIVATION: Genome-scale 'omics' data constitute a potentially rich source of information about biological systems and their function. There is a plethora of tools and methods available to mine omics data. However, the diversity and complexity of different omics data types is a stumbling block for multi-data integration, hence there is a dire need for additional methods to exploit potential synergy from integrated orthogonal data. Rough Sets provide an efficient means to use complex information in classification approaches. Here, we set out to explore the possibilities of Rough Sets to incorporate diverse information sources in a functional classification of unknown genes. RESULTS: We explored the use of Rough Sets for a novel data integration strategy where gene expression data, protein features and Gene Ontology (GO) annotations were combined to describe general and biologically relevant patterns represented by If-Then rules. The descriptive rules were used to predict the function of unknown genes in Arabidopsis thaliana and Schizosaccharomyces pombe. The If-Then rule models showed success rates of up to 0.89 (discriminative and predictive power for both modeled organisms); whereas, models built solely of one data type (protein features or gene expression data) yielded success rates varying from 0.68 to 0.78. Our models were applied to generate classifications for many unknown genes, of which a sizeable number were confirmed either by PubMed literature reports or electronically interfered annotations. Finally, we studied cell cycle protein-protein interactions derived from both tandem affinity purification experiments and in silico experiments in the BioGRID interactome database and found strong experimental evidence for the predictions generated by our models. The results show that our approach can be used to build very robust models that create synergy from integrating gene expression data and protein features. AVAILABILITY: The Rough Set-based method is implemented in the Rosetta toolkit kernel version 1.0.1 available at: http://rosetta.lcb.uu.se/

  • 39.
    Wilczyński, Bartek
    et al.
    Institute of Informatics, Warsaw University Banacha 2, 02-097 Warsaw, Poland; European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
    Hvidsten, Torgeir R.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    A computer scientist's guide to the regulatory genome2010In: Fundamenta Informaticae, ISSN 0169-2968, E-ISSN 1875-8681, Vol. 103, no 1-4, p. 323-332Article in journal (Refereed)
    Abstract [en]

    Recent years have seen a wealth of computational methods applied to problems stemming from molecular biology. In particular, with the completion of many new full genome sequences, great advances have been made in studying the role of non-protein-coding parts of the genome, reshaping our understanding of the role of DNA sequences. Recent breakthroughs in experimental technologies allowing us to inspect the innards of cells on a genomic scale has provided us with unprecedented amounts of data, posing new computational challenges for scientists working to uncover the secrets of life. Due to the binary-like nature of the DNA code and switch-like behavior of many regulatory mechanisms, many of the questions that are currently in focus in biology are surprisingly related to problems that have been of long-term interest to computer scientists. In this review, we present a glimpse into the current state of research in computational methods applied to modeling the regulatory genome. Our aim is to cover current approaches to selected problems from molecular biology that we consider most interesting from the perspective of computer scientists as well as highlight new challenges that will most likely draw the attention of computational biologists in the coming years.

  • 40.
    Önskog, Jenny
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Freyhult, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Landfors, Mattias
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Hvidsten, Torgeir R
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Classification of microarrays: synergistic effects between normalization, gene selection and machine learning2011In: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 12, no 1, article id 390Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Machine learning is a powerful approach for describing and predicting classes in microarray data. Although several comparative studies have investigated the relative performance of various machine learning methods, these often do not account for the fact that performance (e.g. error rate) is a result of a series of analysis steps of which the most important are data normalization, gene selection and machine learning.

    RESULTS: In this study, we used seven previously published cancer-related microarray data sets to compare the effects on classification performance of five normalization methods, three gene selection methods with 21 different numbers of selected genes and eight machine learning methods. Performance in term of error rate was rigorously estimated by repeatedly employing a double cross validation approach. Since performance varies greatly between data sets, we devised an analysis method that first compares methods within individual data sets and then visualizes the comparisons across data sets. We discovered both well performing individual methods and synergies between different methods.

    CONCLUSION: Support Vector Machines with a radial basis kernel, linear kernel or polynomial kernel of degree 2 all performed consistently well across data sets. We show that there is a synergistic relationship between these methods and gene selection based on the T-test and the selection of a relatively high number of genes. Also, we find that these methods benefit significantly from using normalized data, although it is hard to draw general conclusions about the relative performance of different normalization procedures.

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