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  • 101. Kruczyk, Marcin
    et al.
    Przanowski, Piotr
    Swiatek-Machado, Karolina
    Mieczkowski, Jakub
    Dabrowski, Michal
    Wallerman, Ola
    Ronowicz, Anna
    Piotrowski, Arkadiusz
    Wadelius, Claes
    Kaminska, Bozena
    Komorowski, Jan
    Integration of genome-wide of Stat3 binding and epigenetic modifications with transcriptome allowed identification of novel Stat3 target genes in glioma cellsManuskript (preprint) (Annet vitenskapelig)
  • 102. Kruczyk, Marcin
    et al.
    Umer, Husen M.
    Enroth, Stefan
    Komorowski, Jan
    Peak Finder Metaserver - a novel application for finding peaks in ChIP-seq dataInngår i: Artikkel i tidsskrift (Fagfellevurdert)
  • 103. Kruczyk, Marcin
    et al.
    Zetterberg, Henrik
    Hansson, Oskar
    Rolstad, Sindre
    Minthon, Lennart
    Wallin, Anders
    Blennow, Kaj
    Komorowski, Jan
    Andersson, Mats Gunnar
    Monte Carlo feature selection and rule-based models to predict Alzheimer's disease in mild cognitive impairment2012Inngår i: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463Artikkel i tidsskrift (Fagfellevurdert)
  • 104.
    Kuhn, Thomas
    et al.
    Fachhochschule Gelsenkirchen.
    Willighagen, Egon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Zielesny, Achim
    Fachhochschule Gelsenkirchen.
    Steinbeck, Christoph
    European Bioinformatics Institute, Cambridge, UK.
    CDK-Taverna: an open workflow environment for cheminformatics2010Inngår i: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 11, s. 159-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Small molecules are of increasing interest for bioinformatics in areas such as metabolomics and drug discovery. The recent release of large open access chemistry databases generates a demand for flexible tools to process them and discover new knowledge. To freely support open science based on these data resources, it is desirable for the processing tools to be open-source and available for everyone.

    Results

    Here we describe a novel combination of the workflow engine Taverna and the cheminformatics library Chemistry Development Kit (CDK) resulting in a open source workflow solution for cheminformatics. We have implemented more than 160 different workers to handle specific cheminformatics tasks. We describe the applications of CDK-Taverna in various usage scenarios.

    Conclusions

    The combination of the workflow engine Taverna and the Chemistry Development Kit provides the first open source cheminformatics workflow solution for the biosciences. With the Taverna-community working towards a more powerful workflow engine and a more user-friendly user interface, CDK-Taverna has the potential to become a free alternative to existing proprietary workflow tools.

  • 105.
    Kumar Dakshinamurthi, Ashwin
    et al.
    Department of Biotechnology, Sri Venkateswara College of Engineering, Sriperumbudur, Tamilnadu, India.
    Vasagam Chidambaram, Manthira
    Department of Biotechnology, Sri Venkateswara College of Engineering, Sriperumbudur, Tamilnadu, India.
    Anand Manivel, Vivek
    Department of Biotechnology, Sri Venkateswara College of Engineering, Sriperumbudur, Tamilnadu, India.
    Detchanamurthy, Swaminathan
    Department of Chemical and Process Engineering, University of Canterbury, Christchurch, New Zealand.
    Site directed mutagenesis of human Interleukin-2 gene to increase the stability of the gene product: A Bioinformatics Approach2009Inngår i: International Journal of Bioinformatics Research, ISSN 0975–3087, Vol. 1, nr 2, s. 4-13Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Interleukin-2 (IL-2) is an immunoregulatory cytokine whose biological effects are mediated through interaction with specific receptors on the surface of target cells. Due to its presumed role in generating a normal immune response, IL-2 is being evaluated for the treatment of a variety of tumors, in addition to infectious diseases. Main drawback of human IL-2 is that the molecule is relatively unstable. Therefore, with the objective of increasing the stability of the molecule, site directed mutagenesis of human IL-2 gene was carried out. Early studies indicated that mutations at three Cysteine residues (58, 105, 125) which are in the active sites of human IL-2 resulted in the reduced stability as well as the biological activity of the molecule. Therefore, mutations were carried out at the positions of amino acid other than the receptor binding sites at 111Valine to Arginine, 117Lysine to Glutamine and 133 Threonine to Asparagine of the human sequence by comparing it with the bovine sequence which has higher stability than the human counterpart, using SWISS PDB tool. To understand the biological activity of the mutated IL-2, energy minimization studies were carried out using SWISS-PDB. Docking studies were performed to check the reliability of the results using HEX DOCK, ARGUS LAB and PATCH DOCK between the IL-2 receptor and its mutated Ligand. These docking results also confirmed that the reliability of these mutated IL-2 gene. Stability, half life and ADME characteristics of these mutants can be studied in a detailed manner in the in vivo studies. 

  • 106. Kur, Esther
    et al.
    Kim, Jiha
    Tata, Aleksandra
    Comin, Cesar H
    Harrington, Kyle I
    Costa, Luciano da F
    Bentley, Katie
    Gu, Chenghua
    Temporal modulation of collective cell behavior controls vascular network topology.2016Inngår i: eLIFE, E-ISSN 2050-084X, Vol. 5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Vascular network density determines the amount of oxygen and nutrients delivered to host tissues, but how the vast diversity of densities is generated is unknown. Reiterations of endothelial-tip-cell selection, sprout extension and anastomosis are the basis for vascular network generation, a process governed by VEGF/Notch feedback loop. Here, we find that temporal regulation of this feedback loop, a previously unexplored dimension, is the key mechanism to determine vascular density. Iterating between computational modeling and in vivo live imaging, we demonstrate that the rate of tip-cell selection determines the length of linear sprout extension at the expense of branching, dictating network density. We provide the first example of a host tissue-derived signal (Semaphorin3E-Plexin-D1) that accelerates tip cell selection rate, yielding a dense network. We propose that temporal regulation of this critical, iterative aspect of network formation could be a general mechanism, and additional temporal regulators may exist to sculpt vascular topology.

  • 107.
    Künstner, Axel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Birds as a Model for Comparative Genomic Studies2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Comparative genomics provides a tool to investigate large biological datasets, i.e. genomic datasets. In my thesis I focused on inferring patterns of selection in coding and non-coding regions of avian genomes. Until recently, large comparative studies on selection were mainly restricted to model species with sequenced genomes. This limitation has been overcome with advances in sequencing technologies and it is now possible to gather large genomic data sets for non-model species. 

    Next-generation sequencing data was used to study patterns of nucleotide substitutions and from this we inferred how selection has acted in the genomes of 10 non-model bird species. In general, we found evidence for a negative correlation between neutral substitution rate and chromosome size in birds. In a follow up study, we investigated two closely related bird species, to study expression levels in different tissues and pattern of selection. We found that between 2% and 18% of all genes were differentially expressed between the two species.

    We showed that non-coding regions adjacent to genes are under evolutionary constraint in birds, which suggests that noncoding DNA plays an important functional role in the genome. Regions downstream to genes (3’) showed particularly high level of constraint. The level of constraint in these regions was not correlated to the length of untranslated regions, which suggests that other causes play also a role in sequence conservation.

    We compared the rate of nonsynonymous substitutions to the rate of synonymous substitutions in order to infer levels of selection in protein-coding sequences. Synonymous substitutions are often assumed to evolve neutrally. We studied synonymous substitutions by estimating constraint on 4-fold degenerate sites of avian genes and found significant evolutionary constraint on this category of sites (between 24% and 43%). These results call for a reappraisal of synonymous substitution rates being used as neutral standards in molecular evolutionary analysis (e.g. the dN/dS ratio to infer positive selection).

    Finally, the problem of sequencing errors in next-generation sequencing data was investigated. We developed a program that removes erroneous bases from the reads. We showed that low coverage sequencing projects and large genome sequencing projects will especially gain from trimming erroneous reads.

    Delarbeid
    1. Comparative genomics based on massive parallel transcriptome sequencing reveals patterns of substitution and selection across 10 bird species
    Åpne denne publikasjonen i ny fane eller vindu >>Comparative genomics based on massive parallel transcriptome sequencing reveals patterns of substitution and selection across 10 bird species
    Vise andre…
    2010 (engelsk)Inngår i: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 19, nr Suppl.1, s. 266-276Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Next-generation sequencing technology provides an attractive means to obtain largescale sequence data necessary for comparative genomic analysis. To analyse the patterns of mutation rate variation and selection intensity across the avian genome, we performed brain transcriptome sequencing using Roche 454 technology of 10 different non-model avian species. Contigs from de novo assemblies were aligned to the two available avian reference genomes, chicken and zebra finch. In total, we identified 6499 different genes across all 10 species, with ∼1000 genes found in each full run per species. We found evidence for a higher mutation rate of the Z chromosome than of autosomes (male-biased mutation) and a negative correlation between the neutral substitution rate (dS) and chromosome size. Analyses of the mean dN/dS ratio (ω) of genes across chromosomes supported the Hill-Robertson effect (the effect of selection at linked loci) and point at stochastic problems with x as an independent measure of selection. Overall, this study demonstrates the usefulness of next-generation sequencing for obtaining genomic resources for comparative genomic analysis of non-model organisms.

    Emneord
    Avian genomics, Hill-Robertson effect, Male-mutation bias, Next generation sequencing 454, Selection
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-136234 (URN)10.1111/j.1365-294X.2009.04487.x (DOI)000275645700021 ()20331785 (PubMedID)
    Tilgjengelig fra: 2010-12-10 Laget: 2010-12-10 Sist oppdatert: 2018-02-22
    2. Gene content and patterns of gene expression in the flycatcher genome
    Åpne denne publikasjonen i ny fane eller vindu >>Gene content and patterns of gene expression in the flycatcher genome
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Phenotypic evolution may be driven by changes in the sequence of protein-coding genes or by the way (when, where, at what level) proteins are expressed. Generally, our knowledge about the evolution of gene expression is relatively limited, and this is particularly so for wild populations. Collared flycatcher (Ficedula albicollis) and pied flycatcher (F. hypoleuca) are two recently diverged passerine birds, which have been subject to extensive ecological research, including aspects of speciation. We obtained RNA-seq data with Illumina technology from 10 adult individuals per species (five females and five males) using brain, kidney, liver, lung, muscle, skin, ovary, and testis tissue (plus eight embryos of each species). A total of more than 1 billion sequencing reads were assembled into >15.000 gene models for each species. The proportion of differentially expressed genes between species ranged from 8% to 18% per adult tissue. Very few GO categories were found to be overrepresented among differentially expressed genes, which at least in part might reflect that orphan and not yet annotated genes are prone to evolve more rapidly in gene expression level. However, in testis, the category olfactory receptor activity was significantly overrepresented among differentially expressed genes and it is of interest to note that this category of genes is involved in sperm-egg communication and thereby potentially may contribute to reproductive incompatibility between the two species. Genes with a high degree of differentiation in gene expression between species tended to have high rates of sequence evolution (high dN/dS). Overall, this study illustrates both the feasibility and usefulness of deep transcriptome sequencing in non-model organisms.

    Emneord
    Collared flycatcher, Pied flycatcher, Zebra finch, RNA-Seq, Transcriptome sequencing, Species comparison, Gene expression
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-159916 (URN)
    Tilgjengelig fra: 2011-10-11 Laget: 2011-10-11 Sist oppdatert: 2011-11-10
    3. Evolutionary Constraint in Flanking Regions of Avian Genes
    Åpne denne publikasjonen i ny fane eller vindu >>Evolutionary Constraint in Flanking Regions of Avian Genes
    2011 (engelsk)Inngår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 28, nr 9, s. 2481-2489Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    An important comprehension from comparative genomic analysis is that sequence conservation beyond neutral expectations is frequently found outside protein-coding regions, indicating important functional roles of noncoding DNA. Understanding the causes of constraint on noncoding sequence evolution forms an important area of research, not least in light of the importance for understanding the evolution of gene expression. We aligned all orthologous genes of chicken and zebra finch together with 5 kb of their upstream and downstream noncoding sequences, to study the evolution of gene flanking sequences in the avian genome. Using ancestral repeats as a neutral reference, we detected significant evolutionary constraint in the 3' flanking region, highest directly after termination (60%) and then gradually decreasing to about 20% 5 kb downstream. Constraint was higher in annotated 3' untranslated regions (UTRs) than in non-UTRs at the same distance from the stop codon and higher in sequences annotated as microRNA (miRNA)-binding sites than in non-miRNA-binding sites within 3' UTRs. Constraint was also higher when estimated for a smaller data set of genes from more closely related songbird species, indicating turnover of functional elements during avian evolution. On the 5' flanking side constraint was readily seen within the first 125 bp immediately upstream of the start codon (34%) and was about 10% for remaining sequence within 5 kb upstream. Analysis of chicken polymorphism data gave further support for the highest constraint directly before and after the translated region. Finally, we found that genes evolving under the highest constraint measured by d(N)/d(S) also had the highest level of constraint in the 3' flanking region. This study broadens the insights into gene flanking sequence evolution by adding new findings from a vertebrate lineage other than mammals.

    Emneord
    UTR, non-coding DNA, purifying selection, chicken, zebra finch
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-158881 (URN)10.1093/molbev/msr066 (DOI)000294552700010 ()
    Tilgjengelig fra: 2011-09-20 Laget: 2011-09-19 Sist oppdatert: 2018-02-22bibliografisk kontrollert
    4. Significant Selective Constraint at 4-Fold Degenerate Sites in the Avian Genome and Its Consequence for Detection of Positive Selection
    Åpne denne publikasjonen i ny fane eller vindu >>Significant Selective Constraint at 4-Fold Degenerate Sites in the Avian Genome and Its Consequence for Detection of Positive Selection
    2011 (engelsk)Inngår i: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 3, s. 1381-1389Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A major conclusion from comparative genomics is that many sequences that do not code for proteins are conserved beyond neutral expectations, indicating that they evolve under the influence of purifying selection and are likely to have functional roles. Due to the degeneracy of the genetic code, synonymous sites within protein-coding genes have previously been seen as "silent" with respect to function and thereby invisible to selection. However, there are indications that synonymous sites of vertebrate genomes are also subject to selection and this is not necessarily because of potential codon bias. We used divergence in ancestral repeats as a neutral reference to estimate the constraint on 4-fold degenerate sites of avian genes in a whole-genome approach. In the pairwise comparison of chicken and zebra finch, constraint was estimated at 24-32%. Based on three-species alignments of chicken, turkey, and zebra finch, lineage-specific estimates of constraint were 43%, 29%, and 24%, respectively. The finding of significant constraint at 4-fold degenerate sites from data on interspecific divergence was replicated in an analysis of intraspecific diversity in the chicken genome. These observations corroborate recent data from mammalian genomes and call for a reappraisal of the use of synonymous substitution rates as neutral standards in molecular evolutionary analysis, for example, in the use of the well-known d(N)/d(S) ratio and in inferences on positive selection. We show by simulations that the rate of false positives in the detection of positively selected genes and sites increases several-fold at the levels of constraint at 4-fold degenerate sites found in this study.

    Emneord
    Chicken, turkey, zebra finch, 4-fold degenerate sites, purifying selection, nearly neutral theory, comparative genomics
    HSV kategori
    Forskningsprogram
    Biologi med inriktning mot molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-159765 (URN)10.1093/gbe/evr112 (DOI)000301535100030 ()
    Tilgjengelig fra: 2011-10-10 Laget: 2011-10-10 Sist oppdatert: 2018-02-22bibliografisk kontrollert
    5. ConDeTri: A content dependent read trimmer for Illumina data
    Åpne denne publikasjonen i ny fane eller vindu >>ConDeTri: A content dependent read trimmer for Illumina data
    2011 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 10, s. e26314-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    During the last few years, DNA and RNA sequencing have started to play an increasingly important role in biological and medical applications, especially due to the greater amount of sequencing data yielded from the new sequencing machines and the enormous decrease in sequencing costs. Particularly, Illumina/Solexa sequencing has had an increasing impact on gathering data from model and non-model organisms. However, accurate and easy to use tools for quality filtering have not yet been established. We present ConDeTri, a method for content dependent read trimming for next generation sequencing data using quality scores of each individual base. The main focus of the method is to remove sequencing errors from reads so that sequencing reads can be standardized. Another aspect of the method is to incorporate read trimming in next-generation sequencing data processing and analysis pipelines. It can process single-end and paired-end sequence data of arbitrary length and it is independent from sequencing coverage and user interaction. ConDeTri is able to trim and remove reads with low quality scores to save computational time and memory usage during de novo assemblies.  Low coverage or large genome sequencing projects will especially gain from trimming reads.  The method can easily be incorporated into preprocessing and analysis pipelines for Illumina data.

    Availability and implementation:

    Freely available on the web athttp://code.google.com/p/condetri

    Emneord
    Next Generatiom Sequencing, Software, Sequencing Errors
    HSV kategori
    Forskningsprogram
    Bioinformatik
    Identifikatorer
    urn:nbn:se:uu:diva-159761 (URN)10.1371/journal.pone.0026314 (DOI)000296507500049 ()
    Tilgjengelig fra: 2011-10-10 Laget: 2011-10-10 Sist oppdatert: 2017-12-08bibliografisk kontrollert
  • 108.
    Lampa, Samuel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    SWI-Prolog as a Semantic Web Tool for semantic querying in Bioclipse: Integration and performance benchmarking2010Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    The huge amounts of data produced in high-throughput techniques in the life sciences and the need for integration of heterogeneous data from disparate sources in new fields such as Systems Biology and translational drug development require better approaches to data integration. The semantic web is anticipated to provide solutions through new formats for knowledge representation and management. Software libraries for semantic web formats are becoming mature, but there exist multiple tools based on foundationally different technologies. SWI-Prolog, a tool with semantic web support, was integrated into the Bioclipse bio- and cheminformatics workbench software and evaluated in terms of performance against non Prolog-based semantic web tools in Bioclipse, Jena and Pellet, for querying a data set consisting of mostly numerical, NMR shift values, in the semantic web format RDF. The integration has given access to the convenience of the Prolog language for working with semantic data and defining data management workflows in Bioclipse. The performance comparison shows that SWI-Prolog is superior in terms of performance over Jena and Pellet for this specific dataset and suggests Prolog-based tools as interesting for further evaluations.

  • 109.
    Lampa, Samuel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Dahlö, Martin
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Olason, Pall I
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Hagberg, Jonas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Spjuth, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lessons learned from implementing a national infrastructure in Sweden for storage and analysis of next-generation sequencing data2013Inngår i: GigaScience, ISSN 2047-217X, E-ISSN 2047-217X, Vol. 2, nr 1, s. 1-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Analyzing and storing data and results from next-generation sequencing (NGS) experiments is a challenging task, hampered by ever-increasing data volumes and frequent updates of analysis methods and tools. Storage and computation have grown beyond the capacity of personal computers and there is a need for suitable e-infrastructures for processing. Here we describe UPPNEX, an implementation of such an infrastructure, tailored to the needs of data storage and analysis of NGS data in Sweden serving various labs and multiple instruments from the major sequencing technology platforms. UPPNEX comprises resources for high-performance computing, large-scale and high-availability storage, an extensive bioinformatics software suite, up-to-date reference genomes and annotations, a support function with system and application experts as well as a web portal and support ticket system. UPPNEX applications are numerous and diverse, and include whole genome-, de novo- and exome sequencing, targeted resequencing, SNP discovery, RNASeq, and methylation analysis. There are over 300 projects that utilize UPPNEX and include large undertakings such as the sequencing of the flycatcher and Norwegian spruce. We describe the strategic decisions made when investing in hardware, setting up maintenance and support, allocating resources, and illustrate major challenges such as managing data growth. We conclude with summarizing our experiences and observations with UPPNEX to date, providing insights into the successful and less successful decisions made.

  • 110.
    Lang, Daniel
    et al.
    Univ Freiburg, Plant Biotechnol, Fac Biol, Schaenzlestr 1, D-79104 Freiburg, Germany.;Helmholtz Ctr Munich, Plant Genome & Syst Biol, D-85764 Neuherberg, Germany..
    Ullrich, Kristian K.
    Univ Marburg, Plant Cell Biol, Fac Biol, Marburg, Germany.;Max Planck Inst Evolutionary Biol, August Thienemann Str 2, D-24306 Plon, Germany..
    Murat, Florent
    INRA, UMR Genet Divers & Ecophysiol Cereals GDEC 1095, 5 Chemin Beaulieu, F-63100 Clermont Ferrand, France..
    Fuchs, Joerg
    Leibniz Inst Plant Genet & Crop Plant Res IPK, Corrensstr 3, D-06466 Ot Gatersleben, Stadt Seeland, Germany..
    Jenkins, Jerry
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA..
    Haas, Fabian B.
    Univ Marburg, Plant Cell Biol, Fac Biol, Marburg, Germany..
    Piednoel, Mathieu
    Max Planck Inst Plant Breeding Res, Dept Plant Dev Biol, Carl von Linne Weg 10, D-50829 Cologne, Germany..
    Gundlach, Heidrun
    Helmholtz Ctr Munich, Plant Genome & Syst Biol, D-85764 Neuherberg, Germany..
    Van Bel, Michiel
    VIB Ctr Plant Syst Biol, Technol Pk 927, B-9052 Ghent, Belgium.;Univ Ghent, Dept Plant Biotechnol & Bioinformat, Technol Pk 927, B-9052 Ghent, Belgium..
    Meyberg, Rabea
    Univ Marburg, Plant Cell Biol, Fac Biol, Marburg, Germany..
    Vives, Cristina
    UB, UAB, IRTA, CRAG,CSIC, Campus UAB, Barcelona 08193, Spain..
    Morata, Jordi
    UB, UAB, IRTA, CRAG,CSIC, Campus UAB, Barcelona 08193, Spain..
    Symeonidi, Aikaterini
    Univ Marburg, Plant Cell Biol, Fac Biol, Marburg, Germany.;Inst Res Biomed IRB Barcelona, Barcelona, Spain..
    Hiss, Manuel
    Univ Marburg, Plant Cell Biol, Fac Biol, Marburg, Germany..
    Muchero, Wellington
    Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA..
    Kamisugi, Yasuko
    Univ Leeds, Fac Biol Sci, Ctr Plant Sci, Leeds LS2 9JT, W Yorkshire, England..
    Saleh, Omar
    Univ Freiburg, Plant Biotechnol, Fac Biol, Schaenzlestr 1, D-79104 Freiburg, Germany.;Humboldt Univ, Plant Mol Cell Biol, D-10115 Berlin, Germany..
    Blanc, Guillaume
    Aix Marseille Univ, Struct & Genom Informat Lab IGS, IMM FR 3479, CNRS,UMR 7256, Marseille, France..
    Decker, Eva L.
    Univ Freiburg, Plant Biotechnol, Fac Biol, Schaenzlestr 1, D-79104 Freiburg, Germany..
    van Gessel, Nico
    Univ Freiburg, Plant Biotechnol, Fac Biol, Schaenzlestr 1, D-79104 Freiburg, Germany..
    Grimwood, Jane
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA.;US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA..
    Hayes, Richard D.
    US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA..
    Graham, Sean W.
    Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada..
    Gunter, Lee E.
    Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA..
    McDaniel, Stuart F.
    Univ Florida, Dept Biol, Gainesville, FL 32611 USA..
    Hoernstein, Sebastian N. W.
    Univ Freiburg, Plant Biotechnol, Fac Biol, Schaenzlestr 1, D-79104 Freiburg, Germany..
    Larsson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    Li, Fay-Wei
    Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA..
    Perroud, Pierre-Francois
    Univ Marburg, Plant Cell Biol, Fac Biol, Marburg, Germany..
    Phillips, Jeremy
    US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA..
    Ranjan, Priya
    Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA..
    Rokshar, Daniel S.
    US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.;Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA..
    Rothfels, Carl J.
    Univ Calif Berkeley, Univ Herbarium, Berkeley, CA 94720 USA.;Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA..
    Schneider, Lucas
    Univ Marburg, Plant Cell Biol, Fac Biol, Marburg, Germany.;Goethe Univ Frankfurt, Inst Transfus Med & Immunohematol, Sandhofstr 1, D-60528 Frankfurt, Germany.;German Red Cross Blood Serv, Sandhofstr 1, D-60528 Frankfurt, Germany..
    Shu, Shengqiang
    US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA..
    Stevenson, Dennis W.
    New York Bot Garden, Bronx, NY 10458 USA..
    Thummler, Fritz
    Vertis Biotechnol AG, Lise Meitner Str 30, D-85354 Freising Weihenstephan, Germany..
    Tillich, Michael
    Max Planck Inst Mol Plant Physiol, Muehlenberg 1, D-14476 Potsdam, Germany..
    Aguilar, Juan C. Villarreal
    Univ Laval, Dept Biol, Quebec City, PQ G1V 0A6, Canada..
    Widiez, Thomas
    Univ Geneva, Dept Plant Biol, Sci 3, CH-1211 Geneva 4, Switzerland.;Rutgers State Univ, Dept Plant Biol & Pathol, New Brunswick, NJ 08901 USA.;UCB Lyon 1, Lab Reprod & Dev Plantes, Univ Lyon, ENS Lyon,CNRS,INRA, F-69342 Lyon, France..
    Wong, Gane Ka-Shu
    Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada.;Univ Alberta, Dept Med, Edmonton, AB T6G 2E1, Canada.;BGI Shenzhen, Shenzhen 518083, Peoples R China..
    Wymore, Ann
    Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA..
    Zhang, Yong
    Shenzhen Huahan Gene Life Technol Co Ltd, Shenzhen, Peoples R China..
    Zimmer, Andreas D.
    Univ Freiburg, Plant Biotechnol, Fac Biol, Schaenzlestr 1, D-79104 Freiburg, Germany.;Univ Freiburg, Fac Med, Inst Human Genet, Med Ctr, Freiburg, Germany..
    Quatrano, Ralph S.
    Washington Univ, Dept Biol, Campus Box 1137, St Louis, MO 63130 USA..
    Mayer, Klaus F. X.
    Helmholtz Ctr Munich, Plant Genome & Syst Biol, D-85764 Neuherberg, Germany.;Tech Univ Munich, WZW, Munich, Germany..
    Goodstein, David
    US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA..
    Casacuberta, Josep M.
    UB, UAB, IRTA, CRAG,CSIC, Campus UAB, Barcelona 08193, Spain..
    Vandepoele, Klaas
    VIB Ctr Plant Syst Biol, Technol Pk 927, B-9052 Ghent, Belgium.;Univ Ghent, Dept Plant Biotechnol & Bioinformat, Technol Pk 927, B-9052 Ghent, Belgium..
    Reski, Ralf
    Univ Freiburg, Plant Biotechnol, Fac Biol, Schaenzlestr 1, D-79104 Freiburg, Germany.;Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Schaenzlestr 18, D-79104 Freiburg, Germany..
    Cuming, Andrew C.
    Univ Leeds, Fac Biol Sci, Ctr Plant Sci, Leeds LS2 9JT, W Yorkshire, England..
    Tuskan, Gerald A.
    Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA..
    Maumus, Florian
    Univ Paris Saclay, INRA, URGI, F-78026 Versailles, France..
    Salse, Jerome
    INRA, UMR Genet Divers & Ecophysiol Cereals GDEC 1095, 5 Chemin Beaulieu, F-63100 Clermont Ferrand, France..
    Schmutz, Jeremy
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA.;US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA..
    Rensing, Stefan A.
    Univ Marburg, Plant Cell Biol, Fac Biol, Marburg, Germany.;Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Schaenzlestr 18, D-79104 Freiburg, Germany..
    The Physcomitrella patens chromosome-scale assembly reveals moss genome structure and evolution2018Inngår i: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 93, nr 3, s. 515-533Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The draft genome of the moss model, Physcomitrella patens, comprised approximately 2000 unordered scaffolds. In order to enable analyses of genome structure and evolution we generated a chromosome-scale genome assembly using genetic linkage as well as (end) sequencing of long DNA fragments. We find that 57% of the genome comprises transposable elements (TEs), some of which may be actively transposing during the life cycle. Unlike in flowering plant genomes, gene-and TE-rich regions show an overall even distribution along the chromosomes. However, the chromosomes are mono-centric with peaks of a class of Copia elements potentially coinciding with centromeres. Gene body methylation is evident in 5.7% of the protein-coding genes, typically coinciding with low GC and low expression. Some giant virus insertions are transcriptionally active and might protect gametes from viral infection via siRNA mediated silencing. Structure-based detection methods show that the genome evolved via two rounds of whole genome duplications (WGDs), apparently common in mosses but not in liverworts and hornworts. Several hundred genes are present in colinear regions conserved since the last common ancestor of plants. These syntenic regions are enriched for functions related to plant-specific cell growth and tissue organization. The P. patens genome lacks the TE-rich pericentromeric and gene-rich distal regions typical for most flowering plant genomes. More non-seed plant genomes are needed to unravel how plant genomes evolve, and to understand whether the P. patens genome structure is typical for mosses or bryophytes.

  • 111.
    Lapins, Maris
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Worachartcheewan, Apilak
    Spjuth, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Georgiev, Valentin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Prachayasittikul, Virapong
    Nantasenamat, Chanin
    Wikberg, Jarl E. S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    A Unified Proteochemometric Model for Prediction of Inhibition of Cytochrome P450 Isoforms2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 6, s. e66566-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A unified proteochemometric (PCM) model for the prediction of the ability of drug-like chemicals to inhibit five major drug metabolizing CYP isoforms (i.e. CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) was created and made publicly available under the Bioclipse Decision Support open source system at www.cyp450model.org. In regards to the proteochemometric modeling we represented the chemical compounds by molecular signature descriptors and the CYP-isoforms by alignment-independent description of composition and transition of amino acid properties of their protein primary sequences. The entire training dataset contained 63 391 interactions and the best PCM model was obtained using signature descriptors of height 1, 2 and 3 and inducing the model with a support vector machine. The model showed excellent predictive ability with internal AUC = 0.923 and an external AUC = 0.940, as evaluated on a large external dataset. The advantage of PCM models is their extensibility making it possible to extend our model for new CYP isoforms and polymorphic CYP forms. A key benefit of PCM is that all proteins are confined in one single model, which makes it generally more stable and predictive as compared with single target models. The inclusion of the model in Bioclipse Decision Support makes it possible to make virtual instantaneous predictions (∼100 ms per prediction) while interactively drawing or modifying chemical structures in the Bioclipse chemical structure editor.

  • 112. Lappalainen, Tuuli
    et al.
    Sammeth, Michael
    Friedländer, Marc R
    't Hoen, Peter A C
    Monlong, Jean
    Rivas, Manuel A
    Gonzàlez-Porta, Mar
    Kurbatova, Natalja
    Griebel, Thasso
    Ferreira, Pedro G
    Barann, Matthias
    Wieland, Thomas
    Greger, Liliana
    van Iterson, Maarten
    Almlöf, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ribeca, Paolo
    Pulyakhina, Irina
    Esser, Daniela
    Giger, Thomas
    Tikhonov, Andrew
    Sultan, Marc
    Bertier, Gabrielle
    Macarthur, Daniel G
    Lek, Monkol
    Lizano, Esther
    Buermans, Henk P J
    Padioleau, Ismael
    Schwarzmayr, Thomas
    Karlberg, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ongen, Halit
    Kilpinen, Helena
    Beltran, Sergi
    Gut, Marta
    Kahlem, Katja
    Amstislavskiy, Vyacheslav
    Stegle, Oliver
    Pirinen, Matti
    Montgomery, Stephen B
    Donnelly, Peter
    McCarthy, Mark I
    Flicek, Paul
    Strom, Tim M
    Lehrach, Hans
    Schreiber, Stefan
    Sudbrak, Ralf
    Carracedo, Angel
    Antonarakis, Stylianos E
    Häsler, Robert
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    van Ommen, Gert-Jan
    Brazma, Alvis
    Meitinger, Thomas
    Rosenstiel, Philip
    Guigó, Roderic
    Gut, Ivo G
    Estivill, Xavier
    Dermitzakis, Emmanouil T
    Transcriptome and genome sequencing uncovers functional variation in humans2013Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 501, nr 7468, s. 506-511Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.

  • 113.
    Larsson, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi.
    AliView: a fast and lightweight alignment viewer and editor for large data sets2014Inngår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 30, nr 22, s. 3276-3278Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Summary: AliView is an alignment viewer and editor designed tomeet the requirements of next generation sequencing era phyloge-netic datasets. AliView handles alignments of unlimited size in theformats most commonly used, i.e. Fasta, Phylip, Nexus, Clustal andMSF. The intuitive graphical interface makes it easy to inspect, sort,delete, merge and realign sequences as part of the manual filteringprocess of large data sets. AliView also works as an easy to usealignment editor for small as well as large data sets.Availability: AliView is released as open-source software under theGNU General Public License, version 3.0 (GPLv3), and is availableat GitHub (www.github.com/AliView). The program is cross-platformand extensively tested on Linux, Mac OS X and Windows systems.Downloads and help are available at http://ormbunkar.se/aliviewContact: anders.larsson@ebc.uu.seSupplementary information:

  • 114. Li, Xinlei
    et al.
    Dong, Feng
    Lei, Fumin
    Alström, Per
    Zhang, Ruiying
    Ödeen, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Zooekologi.
    Fjeldså, Jon
    Ericson, Per G. P.
    Zou, Fasheng
    Yang, Xiaojun
    Shaped by uneven Pleistocene climate: mitochondrial phylogeographic pattern and population history of White Wagtail Motacilla alba (Aves: Passeriformes).2016Inngår i: Journal of Avian Biology, ISSN 0908-8857, E-ISSN 1600-048X, Vol. 47, s. 263-274Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We studied the phylogeography and population history of the white wagtail Motacilla alba, which has a vast breeding range, covering areas with different Pleistocene climatic histories. The mitochondrial NADH dehydrogenase subunit II gene (ND2) and Control Region (CR) were analyzed for 273 individuals from 45 localities. Our data comprised all nine subspecies of white wagtail. Four primary clades were inferred (M, N, SW and SE), with indications of M. grandis being nested within M. alba. The oldest split was between two haplotypes from the endemic Moroccan M. a. subpersonata (clade M) and the others, at 0.63–0.96 Mya; other divergences were at 0.31–0.38 Mya. The entire differentiation falls within the part of the Pleistocene characterized by Milankovitch cycles of large amplitudes and durations. Clade N was distributed across the northern Palearctic; clade SW in southwestern Asia plus the British Isles and was predicted by Ecological niche models (ENMs) to occur also in central and south Europe; and clade SE was distributed in central and east Asia. e deep divergence within M. a. subpersonata may reflect retention of ancestral haplotypes. Regional differences in historical climates have had different impacts on different populations: clade N expanded after the last glacial maximum (LGM), whereas milder Pleistocene climate of east Asia allowed clade SE a longer expansion time (since MIS 5); clade SW expanded over a similarly long time as clade SE, which is untypical for European species. ENMs supported these conclusions in that the northern part of the Eurasian continent was unsuitable during the LGM, whereas southern parts remained suitable. e recent divergences and poor structure in the mitochondrial tree contrasts strongly with the pronounced, well defined phenotypical differentiation, indicating extremely fast plumage divergence. 

  • 115. Lin, Yao-Cheng
    et al.
    Wang, Jing
    Delhomme, Nicolas
    Schiffthaler, Bastian
    Sundström, Görel
    Zuccolo, Andrea
    Nystedt, Björn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hvidsten, Torgeir R.
    de la Torre, Amanda
    Cossu, Rosa M.
    Höppner, Marc P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Lantz, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Scofield, Douglas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Zamani, Neda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Johansson, Anna C. V.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mannapperuma, Chanaka
    Robinson, Kathryn M.
    Mähler, Niklas
    Leitch, Ilia J.
    Pellicer, Jaume
    Park, Eung-Jun
    Van Montagu, Marc
    Van de Peer, Yves
    Grabherr, Manfred
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Jansson, Stefan
    Ingvarsson, Pär K.
    Street, Nathaniel R.
    Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen2018Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, nr 46, s. E10970-E10978Artikkel i tidsskrift (Fagfellevurdert)
  • 116.
    Liu, Xiaodong
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Prediction of drug class and adverse sideeffects based on induced gene expressionprofiles - a feasability study2013Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
    Abstract [en]

    One of the core businesses of biomedical study is to establish diseases/genes/drugs connections, which still remains as a fundamental challenge in today’s pharmacological and medical research due to the limited numbers of effective tools. Gene-expression profiling has historically served as a valuable resource for elucidating the mechanisms underlying biological pathways, for instance, the molecular pathological mechanism of certain diseases in biomedicine. However, few efforts have been put into exploring deeper knowledge of medication by means of gene expression profiling. The aim of the project reported here was to establish a systematic approach to the discovery of functional connections among gene expression, drug classification and drug action using statistical (machine) learning techniques available and refined in R and in RapidMiner. Based on the data derived from “Connectivity Map”resource (a large collection of 22000-dimensional gene-expression profiles induced in cultured human cells when treated with 1309 different drug molecules) the feasibility to establish a well performing classifier which can predict drug groups according to the Anatomical Therapeutic Chemical (ATC) system was explored. The same kind of classification approach was also applied to predict adverse side effects of drugs, available in the SIDER online database, using the same “Connectivity Map” gene expression data. In order to avoid information leaks between the classifier design and the subsequent test on new examples, which could future lead to over-optimistic conclusions, all feasibility studies were performed using carefully designed cross validation procedures. Although we succeeded in building a well performing classifier for one certain ATC group on the second level, the overall performance of classifiers when evaluated properly (no information leaks) was less promising than expected, for both ATC and side effect prediction. Therefore the main conclusion is that the “Connectivity Map” resource seems to contain surprisingly limited information with respect to these two prediction tasks.

  • 117. Llorens, Carlos
    et al.
    Futami, Ricardo
    Covelli, Laura
    Domínguez-Escribá, Laura
    Viu, Jose M
    Tamarit, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Aguilar-Rodríguez, Jose
    Vicente-Ripolles, Miguel
    Fuster, Gonzalo
    Bernet, Guillermo P
    Maumus, Florian
    Munoz-Pomer, Alfonso
    Sempere, Jose M
    Latorre, Amparo
    Moya, Andres
    The Gypsy Database (GyDB) of mobile genetic elements: release 2.0.2011Inngår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 39, nr Database issueArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This article introduces the second release of the Gypsy Database of Mobile Genetic Elements (GyDB 2.0): a research project devoted to the evolutionary dynamics of viruses and transposable elements based on their phylogenetic classification (per lineage and protein domain). The Gypsy Database (GyDB) is a long-term project that is continuously progressing, and that owing to the high molecular diversity of mobile elements requires to be completed in several stages. GyDB 2.0 has been powered with a wiki to allow other researchers participate in the project. The current database stage and scope are long terminal repeats (LTR) retroelements and relatives. GyDB 2.0 is an update based on the analysis of Ty3/Gypsy, Retroviridae, Ty1/Copia and Bel/Pao LTR retroelements and the Caulimoviridae pararetroviruses of plants. Among other features, in terms of the aforementioned topics, this update adds: (i) a variety of descriptions and reviews distributed in multiple web pages; (ii) protein-based phylogenies, where phylogenetic levels are assigned to distinct classified elements; (iii) a collection of multiple alignments, lineage-specific hidden Markov models and consensus sequences, called GyDB collection; (iv) updated RefSeq databases and BLAST and HMM servers to facilitate sequence characterization of new LTR retroelement and caulimovirus queries; and (v) a bibliographic server. GyDB 2.0 is available at http://gydb.org.

  • 118.
    Lopes Pinto, Fernando
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap.
    Development of Molecular Biology and Bioinformatics Tools: From Hydrogen Evolution to Cell Division in Cyanobacteria2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The use of fossil fuels presents a particularly interesting challenge - our society strongly depends on coal and oil, but we are aware that their use is damaging the environment. Currently, this awareness is gaining momentum, and pressure to evolve towards an energetically cleaner planet is very strong. Molecular hydrogen (H2) is an environmentally suitable energy carrier that could initially supplement or even substitute fossil fuels.

    Ideally, the primary energy source to produce hydrogen gas should be renewable, and the process of conversion back to energy without polluting emissions, making this cycle environmentally clean. Photoconversion of water to hydrogen can be achieved using the following strategies: 1) the use of photochemical fuel cells, 2) by applying photovoltaics, or 3) by promoting production of hydrogen by photosynthetic microorganisms, either phototrophic anoxygenic bacteria and cyanobacteria or eukaryotic green algae. For photobiological H2 production cyanobacteria are among the ideal candidates since they: a) are capable of H2 evolution, and b) have simple nutritional requirements - they can grow in air (N2 and CO2), water and mineral salts, with light as the only energy source.

    As this project started, a vision and a set of overall goals were established. These postulated that improved H2 production over a long period demanded: 1) selection of strains taking in consideration their specific hydrogen metabolism, 2) genetic modification in order to improve the H2 evolution, and 3) cultivation conditions in bioreactors should be exmined and improved. Within these goals, three main research objectives were set: 1) update and document the use of cyanobacteria for hydrogen production, 2) create tools to improve molecular biology work at the transcription analysis level, and 3) study cell division in cyanobacteria.

    This work resulted in: 1) the publication of a review on hydrogen evolution by cyanobacteria, 2) the development of tools to assist understanding of transcription, and 3) the start of a new fundamental research approach to ultimately improve the yield of H2 evolution by cyanobacteria.

    Delarbeid
    1. A brief look at three decades of hydrogen evolution by Cyanobacteria.
    Åpne denne publikasjonen i ny fane eller vindu >>A brief look at three decades of hydrogen evolution by Cyanobacteria.
    2002 (engelsk)Inngår i: International Journal of Hydrogen Energy, Vol. 27, s. 1209-1215Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-44028 (URN)
    Tilgjengelig fra: 2008-10-17 Laget: 2008-10-17 Sist oppdatert: 2009-11-13
    2. Analysis of current and alternative phenol based RNA extraction methodologies for cyanobacteria
    Åpne denne publikasjonen i ny fane eller vindu >>Analysis of current and alternative phenol based RNA extraction methodologies for cyanobacteria
    2009 (engelsk)Inngår i: BMC Molecular Biology, ISSN 1471-2199, E-ISSN 1471-2199, Vol. 10, s. 79-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: The validity and reproducibility of gene expression studies depend on the quality of extracted RNA and the degree of genomic DNA contamination. Cyanobacteria are gram-negative prokaryotes that synthesize chlorophyll a and carry out photosynthetic water oxidation. These organisms possess an extended array of secondary metabolites that impair cell lysis, presenting particular challenges when it comes to nucleic acid isolation. Therefore, we used the NHM5 strain of Nostoc punctiforme ATCC 29133 to compare and improve existing phenol based chemistry and procedures for RNA extraction.

    RESULTS: With this work we identify and explore strategies for improved and lower cost high quality RNA isolation from cyanobacteria. All the methods studied are suitable for RNA isolation and its use for downstream applications. We analyse different Trizol based protocols, introduce procedural changes and describe an alternative RNA extraction solution.

    CONCLUSION: It was possible to improve purity of isolated RNA by modifying protocol procedures. Further improvements, both in RNA purity and experimental cost, were achieved by using a new extraction solution, PGTX.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-110391 (URN)10.1186/1471-2199-10-79 (DOI)000269645600001 ()19660145 (PubMedID)
    Tilgjengelig fra: 2009-11-13 Laget: 2009-11-13 Sist oppdatert: 2017-12-12
    3. Generation of non-genomic oligonucleotide tag sequences for RNA template-specific PCR
    Åpne denne publikasjonen i ny fane eller vindu >>Generation of non-genomic oligonucleotide tag sequences for RNA template-specific PCR
    2006 (engelsk)Inngår i: BMC Biotechnology, ISSN 1472-6750, E-ISSN 1472-6750, Vol. 6, s. 31-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background

    In order to overcome genomic DNA contamination in transcriptional studies, reverse template-specific polymerase chain reaction, a modification of reverse transcriptase polymerase chain reaction, is used. The possibility of using tags whose sequences are not found in the genome further improves reverse specific polymerase chain reaction experiments. Given the absence of software available to produce genome suitable tags, a simple tool to fulfill such need was developed.

    Results

    The program was developed in Perl, with separate use of the basic local alignment search tool, making the tool platform independent (known to run on Windows XP and Linux). In order to test the performance of the generated tags, several molecular experiments were performed. The results show that Tagenerator is capable of generating tags with good priming properties, which will deliberately not result in PCR amplification of genomic DNA.

    Conclusion

    The program Tagenerator is capable of generating tag sequences that combine genome absence with good priming properties for RT-PCR based experiments, circumventing the effects of genomic DNA contamination in an RNA sample.

    Emneord
    Tagenerator, RT-PCR
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-81352 (URN)10.1186/1472-6750-6-31 (DOI)16820068 (PubMedID)
    Tilgjengelig fra: 2006-08-18 Laget: 2006-08-18 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. Webtag: A new web tool providing tags/anchors for RT-PCR experiments with prokaryotes
    Åpne denne publikasjonen i ny fane eller vindu >>Webtag: A new web tool providing tags/anchors for RT-PCR experiments with prokaryotes
    2007 (engelsk)Inngår i: BMC Biotechnology, ISSN 1472-6750, E-ISSN 1472-6750, Vol. 7, s. 73-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Webtag is a tool providing oligonucleotide sequences (usually called tags or anchors) that are absent from a specified genome. These tags/anchors can be appended to gene specific primers for reverse transcriptase polymerase chain reaction experiments, circumventing genomic DNA contamination. Results: The use of a relational database, in conjunction with a series of scripts written in PHP and Perl, allows the user to rapidly obtain tags that are: 1) suitable for a specific organism, and 2) compatible with other oligonucleotides to be used in the experimental procedures. Conclusion: This new web tool allows scientists to easily and rapidly obtain suitable tags for RTPCR experiments, and is available at http://www.egs.uu.se/software/webtag/.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-13840 (URN)10.1186/1472-6750-7-73 (DOI)000251903100001 ()17961214 (PubMedID)
    Tilgjengelig fra: 2008-01-28 Laget: 2008-01-28 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    5. A guide for in-house design of template-switch-based 5' rapid amplification of cDNA ends systems
    Åpne denne publikasjonen i ny fane eller vindu >>A guide for in-house design of template-switch-based 5' rapid amplification of cDNA ends systems
    2009 (engelsk)Inngår i: Analytical biochemistry, ISSN 1096-0309Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Rapid amplification of cDNA ends (RACE) is an established strategy used to determine the transcription start point(s) and the 5' untranslated region(s) of mRNA. Different approaches to perform 5' RACE are available, and one particularly simple and powerful strategy is based on a phenomenon called template-switching. We investigated different aspects of template-switch-based 5' RACE, and we describe the different steps leading to the in-house development of a complete 5' RACE system-from oligonucleotide design to polymerase chain reaction (PCR) amplification. We show that the resulting system is reliable, time-efficient, and inexpensive.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-110392 (URN)10.1016/j.ab.2009.10.022 (DOI)000274163900015 ()19837043 (PubMedID)
    Tilgjengelig fra: 2009-11-13 Laget: 2009-11-13 Sist oppdatert: 2012-08-22
    6. Evidence for transcription of three genes with characteristics of hydrogenases in the green alga Chlamydomonas noctigama
    Åpne denne publikasjonen i ny fane eller vindu >>Evidence for transcription of three genes with characteristics of hydrogenases in the green alga Chlamydomonas noctigama
    2010 (engelsk)Inngår i: International journal of hydrogen energy, ISSN 0360-3199, E-ISSN 1879-3487, Vol. 35, nr 3, s. 1074-1088Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Some green algae have shown the ability to produce hydrogen under anaerobic conditions. The production of hydrogen in green algae is catalyzed by hydrogenases, which are small monomeric enzymes with high conversion efficiency and high oxygen sensitivity. Most green algae analyzed to date where hydrogenase genes are detected, have been shown to contain two distinct hydrogenases. However, very little is known about which functions the two different enzymes represent. There are also many unknowns within the mechanisms behind hydrogen production as to the roles hydrogenases play under different conditions, and consequently also about the potential for optimization of a hydrogen production process which could be found in this respect. This study focuses on the possibility for the presence of more than two hydrogenases in a single green alga. A large number of degenerate primers were designed and used to produce 3′-RACE products, which in turn were used to design gene specific primers used for PCR and 5′-RACE reactions. The sequences were aligned with known algal hydrogenases to identify products which had homology to these. Products where homology was identified were then explored further. A high number of clones from each band were sequenced to identify products with similar lengths which would not show up as separate bands on a gel. Sequences found to have homology with algal hydrogenases were translated into putative amino acid sequences and analyzed further to obtain detailed information about the presence of specific amino acids with known functions in the enzyme. This information was used to evaluate the likelihood of these transcripts coding for true hydrogenases, versus hydrogenase-like or narf-like proteins. We here present evidence showing that Chlamydomonas noctigama is able to transcribe three genes which share a significant number of characteristics with other known algal FeFe-hydrogenases. The three genes have been annotated HYDA1, HYDA2 and HYDA3.

    Emneord
    Algae, Chlamydomonas noctigama, HYDA, Hydrogen, Hydrogenase
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-110841 (URN)10.1016/j.ijhydene.2009.10.091 (DOI)000274944000023 ()
    Tilgjengelig fra: 2009-11-26 Laget: 2009-11-26 Sist oppdatert: 2017-12-12
    7. FtsZ in Anabaena sp. PCC 7120; initial characterization of ftsZ transcription and evidence of in vitro FtsZ degradation.
    Åpne denne publikasjonen i ny fane eller vindu >>FtsZ in Anabaena sp. PCC 7120; initial characterization of ftsZ transcription and evidence of in vitro FtsZ degradation.
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet (populærvitenskap, debatt, mm))
    Identifikatorer
    urn:nbn:se:uu:diva-110839 (URN)
    Tilgjengelig fra: 2009-11-26 Laget: 2009-11-26 Sist oppdatert: 2009-11-27
  • 119.
    Lopes Pinto, Fernando
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Fysiologisk botanik.
    Svensson, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Molekylär evolution.
    Lindblad, Peter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Fysiologisk botanik.
    Generation of non-genomic oligonucleotide tag sequences for RNA template-specific PCR2006Inngår i: BMC Biotechnology, ISSN 1472-6750, E-ISSN 1472-6750, Vol. 6, s. 31-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    In order to overcome genomic DNA contamination in transcriptional studies, reverse template-specific polymerase chain reaction, a modification of reverse transcriptase polymerase chain reaction, is used. The possibility of using tags whose sequences are not found in the genome further improves reverse specific polymerase chain reaction experiments. Given the absence of software available to produce genome suitable tags, a simple tool to fulfill such need was developed.

    Results

    The program was developed in Perl, with separate use of the basic local alignment search tool, making the tool platform independent (known to run on Windows XP and Linux). In order to test the performance of the generated tags, several molecular experiments were performed. The results show that Tagenerator is capable of generating tags with good priming properties, which will deliberately not result in PCR amplification of genomic DNA.

    Conclusion

    The program Tagenerator is capable of generating tag sequences that combine genome absence with good priming properties for RT-PCR based experiments, circumventing the effects of genomic DNA contamination in an RNA sample.

  • 120.
    Lundin, Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    AutoPhylo, a bioinformatic tool for identifying and retrieving sequences2010Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    The task of constructing a molecular phylogenetic tree consists of finding homologous sequences, making a multiple sequence alignment, perhaps removing gaps and ambiguous positions in the alignment and finally phylogenetically inferring the tree with various evolutionary models. Often there is a need to refine the tree by removing inappropriate sequences. For each step of this process there is a tool to accomplish the task. Starting with a sequence of interest BLAST (Basic Local Alignment Search Tool) is used to find homologous sequences from various databases. Then multiple sequence alignment programs such as MUSCLE or CLUSTAL can be used to align the sequences. In the alignment there are often regions of gaps and ambiguous positions that can be identified and removed with programs such as GBlocks. Finally, using the alignment a phylogenetic tree can be reconstructed using selected methods and models. Depending on the scientific goals and data, this process generally needs to be repeated several times in order to “refine” the tree. To construct a tree of correct phylogeny “true” homologous positions in an alignment must beused. In addition, if the tree is to reconstruct the correct relationship among species (rather than just the genes), then it is also necessary to use orthologous sequences, rather than sequences that have undergone duplications (paralogs). To further complicate tree reconstruction there are technical problems such as long branch attraction (where fast evolving sequences cluster together even if they are unrelated) and horizontal gene transfer (where cells that can be unrelated exchange genes) that could mislead the phylogeny. At present there is no effective program that is sophisticated enough to correct these kinds of problems without careful manual examination. However, many of these steps are simple and repetitive. It is the goal of bioinformatics to automate as many of these simple tedious steps as possible, in order to allow large amounts of data to be processed quickly and accurately. In this paper a tool that streamlines the phylogenetic tree reconstruction process is presented. The tool, named AutoPhylo, identifies and retrieves sequences from NCBI (database collection) or a user-defined local database via BLAST searches. These sequences are then used to construct a tree that can be examined with a graphical user interface (GUI). The GUI allows the user to identify and remove unwanted sequences in order to refine the tree. The sequences are retrieved in groups that have one or more queries that limits the selection to specific species, genes or others valid NCBI queries. Some tests are applied to show that the program is useful and is able to accelerate subroutines of the process.

  • 121.
    Lundén, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Mathematical modeling of insulin response in encapsulated islets of Langerhans2014Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    Transplantation of the islets of Langerhans is a promising technique for restoring the impairedinsulin production in brittle type 1 diabetics. The downside is that the patient will have to takeimmunosuppressant drugs in order to protect the islet cells from the immune system. Donorsare also sparse, making the quest of finding sufficient amounts of islets for transplantationhard. Encapsulation of the islets of Langerhans has been proposed as a means of protectingthe cells from the immune system taking away the need for immunosuppresives. The mostcommon encapsulation technique is extravascular capsules, which are categorized into micro-and macrocapsules. The microcapsules hold only one or a small set of islet whereas themacrocapsules hold a large quantity of islets.This thesis investigates the encapsulation impact on the beta-cells rapid insulin response torising plasma glucose levels. This was done by simulating the glucose-insulin system inMATLAB with included encapsulation of the islets. Two current macro-encapsulation set upswere used in the model, Beta-Air and ViaCyte devices, and they were compared against anormal case. The results showed that the Beta-Air device would not be able to restorenormoglycemia in a T1DM patient but rather showed a delay in insulin response, while theViaCyte device could mimic the normal case well.

  • 122.
    Mahjani, Behrang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Toor, Salman
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Software as a service in analysis of quantitative trait loci2016Rapport (Annet vitenskapelig)
  • 123.
    Mahjani, Behrang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Toor, Salman
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Holmgren, Sverker
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    A flexible computational framework using R and Map-Reduce for permutation tests of massive genetic analysis of complex traits2017Inngår i: IEEE/ACM Transactions on Computational Biology & Bioinformatics, ISSN 1545-5963, E-ISSN 1557-9964, Vol. 14, s. 381-392Artikkel i tidsskrift (Fagfellevurdert)
  • 124.
    Mahjani, Behrang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Toor, Salman
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Holmgren, Sverker
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    QTL as a service: PruneDIRECT for multi-dimensional QTL scans in cloud settings2016Inngår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811Artikkel i tidsskrift (Annet vitenskapelig)
  • 125.
    Mahmutovic, Anel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Reaction-Diffusion kinetics of Protein DNA Interactions2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Transcription factors need to rapidly find one specific binding site among millions of nonspecific sites on the chromosomal DNA. In this thesis I use various aspects of reaction-diffusion theory to investigate the interaction between proteins and DNA and to explain the searching, finding and binding to specific operator sites. Using molecular dynamics methods we calculate the free energy profile for the model protein LacI as it leaves a nonspecific stretch of DNA and as it slides along DNA. Based on the free energy profiles we estimate the microscopic dissociation rate constant, kdmicro ~1.45×104s-1, and the 1D diffusion coefficient, D1 ~ 0.05-0.29 μm2s-1 (2-40μs to slide 1 basepair (bp)). At a non-atomistic level of detail we estimate the number of microscopic rebindings before a macroscopic dissociation occurs which leads to the  macroscopic residence time, τDmacro ~ 48±12ms resulting in a in vitro sliding length estimate of 135-345bp.

    When we fit the DNA interaction parameters for in vivo conditions to recent single molecule in vivo experiments we conclude that neither hopping nor intersegment transfer contribute to the target search for the LacI dimer, that it appears to bind the specific Osym operator site as soon as it slides into it, and that the sliding length is around 40bp in the cell. The estimated in vivo D1 ~ 0.025 μm2s-1 is higher than expected from estimates of D1 based on viscosity and the atomistic simulations. Surprisingly, we were also forced to conclude that the nonspecific association for the LacI dimer appeared reaction limited which is in conflict with the free energy profile. This inconsistency is resolved by allowing for steric effects. Using reaction-diffusion theory and simulations we show that an apparent reaction limited association can be diffusion limited if geometry and steric effects are taken into account. Furthermore, the simulations show that a protein binds ~2 times faster to a DNA molecule with a helical reactive patch than to a stripe patch running along the length of the DNA. This facilitated binding has a direct impact on the search time especially in the presence of other DNA binding proteins.

    Delarbeid
    1. What matters for lac repressor search in vivo-sliding, hopping, intersegment transfer, crowding on DNA or recognition?
    Åpne denne publikasjonen i ny fane eller vindu >>What matters for lac repressor search in vivo-sliding, hopping, intersegment transfer, crowding on DNA or recognition?
    2015 (engelsk)Inngår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 43, nr 7, s. 3454-3464Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We have investigated which aspects of transcription factor DNA interactions are most important to account for the recent in vivo search time measurements for the dimeric lac repressor. We find the best agreement for a sliding model where non-specific binding to DNA is improbable at first contact and the sliding LacI protein binds at high probability when reaching the specific O-sym operator. We also find that the contribution of hopping to the overall search speed is negligible although physically unavoidable. The parameters that give the best fit reveal sliding distances, including hopping, close to what has been proposed in the past, i.e. similar to 40 bp, but with an unexpectedly high 1D diffusion constant on non-specific DNA sequences. Including a mechanism of inter-segment transfer between distant DNA segments does not bring down the 1D diffusion to the expected fraction of the in vitro value. This suggests a mechanism where transcription factors can slide less hindered in vivo than what is given by a simple viscosity scaling argument or that a modification of the model is needed. For example, the estimated diffusion rate constant would be consistent with the expectation if parts of the chromosome, away from the operator site, were inaccessible for searching.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-256544 (URN)10.1093/nar/gkv207 (DOI)000354722500012 ()25779051 (PubMedID)
    Tilgjengelig fra: 2015-06-25 Laget: 2015-06-24 Sist oppdatert: 2017-12-04bibliografisk kontrollert
    2. Lost in presumption: stochastic reactions in spatial models
    Åpne denne publikasjonen i ny fane eller vindu >>Lost in presumption: stochastic reactions in spatial models
    2012 (engelsk)Inngår i: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 9, nr 12, s. 1163-1166Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Physical modeling is increasingly important for generating insights into intracellular processes. We describe situations in which combined spatial and stochastic aspects of chemical reactions are needed to capture the relevant dynamics of biochemical systems.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-191793 (URN)10.1038/nmeth.2253 (DOI)000312093500016 ()
    Tilgjengelig fra: 2013-01-14 Laget: 2013-01-14 Sist oppdatert: 2017-12-06
    3. Transcription-factor binding and sliding on DNA studied using micro- and macroscopic models
    Åpne denne publikasjonen i ny fane eller vindu >>Transcription-factor binding and sliding on DNA studied using micro- and macroscopic models
    Vise andre…
    2013 (engelsk)Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, nr 49, s. 19796-19801Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Transcription factors search for specific operator sequences by alternating rounds of 3D diffusion with rounds of 1D diffusion (sliding) along the DNA. The details of such sliding have largely been beyond direct experimental observation. For this purpose we devised an analytical formulation of umbrella sampling along a helical coordinate, and from extensive and fully atomistic simulations we quantified the free-energy landscapes that underlie the sliding dynamics and dissociation kinetics for the LacI dimer. The resulting potential of mean force distributions show a fine structure with an amplitude of 1 k(B)T for sliding and 12 kBT for dissociation. Based on the free-energy calculations the repressor slides in close contact with DNA for 8 bp on average before making a microscopic dissociation. By combining the microscopic molecular-dynamics calculations with Brownian simulation including rotational diffusion from the microscopically dissociated state we estimate a macroscopic residence time of 48 ms at the same DNA segment and an in vitro sliding distance of 240 bp. The sliding distance is in agreement with previous in vitro sliding-length estimates. The in vitro prediction for the macroscopic residence time also compares favorably to what we measure by single-molecule imaging of nonspecifically bound fluorescently labeled LacI in living cells. The investigation adds to our understanding of transcription-factor search kinetics and connects the macro-/mesoscopic rate constants to the microscopic dynamics.

    Emneord
    facilitated diffusion, lac operon, lac repressors, gene regulation
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-213898 (URN)10.1073/pnas.1307905110 (DOI)000327744900041 ()
    Eksternt samarbeid:
    Tilgjengelig fra: 2014-01-06 Laget: 2014-01-05 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    4. MesoRD 1.0: Stochastic reaction-diffusion simulations in the microscopic limit
    Åpne denne publikasjonen i ny fane eller vindu >>MesoRD 1.0: Stochastic reaction-diffusion simulations in the microscopic limit
    2012 (engelsk)Inngår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 28, nr 23, s. 3155-3157Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    MesoRD is a tool for simulating stochastic reaction-diffusion systems as modeled by the reaction diffusion master equation. The simulated systems are defined in the Systems Biology Markup Language with additions to define compartment geometries. MesoRD 1.0 supports scale-dependent reaction rate constants and reactions between reactants in neighbouring subvolumes. These new features make it possible to construct physically consistent models of diffusion-controlled reactions also at fine spatial discretization.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-192453 (URN)10.1093/bioinformatics/bts584 (DOI)000311902700025 ()
    Tilgjengelig fra: 2013-01-23 Laget: 2013-01-21 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    5. The lac repressor displays facilitated diffusion in living cells
    Åpne denne publikasjonen i ny fane eller vindu >>The lac repressor displays facilitated diffusion in living cells
    Vise andre…
    2012 (engelsk)Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 336, nr 6088, s. 1595-1598Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Transcription factors (TFs) are proteins that regulate the expression of genes by binding sequence-specific sites on the chromosome. It has been proposed that to find these sites fast and accurately, TFs combine one-dimensional (1D) sliding on DNA with 3D diffusion in the cytoplasm. This facilitated diffusion mechanism has been demonstrated in vitro, but it has not been shown experimentally to be exploited in living cells. We have developed a single-molecule assay that allows us to investigate the sliding process in living bacteria. Here we show that the lac repressor slides 45 ± 10 base pairs on chromosomal DNA and that sliding can be obstructed by other DNA-bound proteins near the operator. Furthermore, the repressor frequently (>90%) slides over its natural lacO(1) operator several times before binding. This suggests a trade-off between rapid search on nonspecific sequences and fast binding at the specific sequence.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-176861 (URN)10.1126/science.1221648 (DOI)000305507500062 ()22723426 (PubMedID)
    Eksternt samarbeid:
    Tilgjengelig fra: 2012-06-26 Laget: 2012-06-26 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    6. The helical structure of DNA facilitates binding
    Åpne denne publikasjonen i ny fane eller vindu >>The helical structure of DNA facilitates binding
    2016 (engelsk)Inngår i: Journal of Physics A: Mathematical and Theoretical, ISSN 1751-8113, E-ISSN 1751-8121, Vol. 9, nr 36, artikkel-id 364002Artikkel i tidsskrift (Annet vitenskapelig) Published
    Abstract [en]

    The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction-diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general.

    Emneord
    reaction-diffusion equation; steric constraints; helix geometry; diffusion limited
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-263526 (URN)10.1088/1751-8113/49/36/364002 (DOI)000383512000002 ()
    Forskningsfinansiär
    EU, European Research CouncilKnut and Alice Wallenberg Foundation
    Tilgjengelig fra: 2015-10-02 Laget: 2015-10-02 Sist oppdatert: 2017-12-01bibliografisk kontrollert
  • 126.
    Mahmutovic, Anel
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Berg, Otto G
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Elf, Johan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    What matters for lac repressor searchinvivo ––sliding, hopping, intersegment transfer, crowding on DNA or recognition?2015Inngår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 43, nr 7, s. 3454-3464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have investigated which aspects of transcription factor DNA interactions are most important to account for the recent in vivo search time measurements for the dimeric lac repressor. We find the best agreement for a sliding model where non-specific binding to DNA is improbable at first contact and the sliding LacI protein binds at high probability when reaching the specific Osym operator. We also find that the contribution of hopping to the overall search speed is negligible although physically unavoidable. The parameters that give the best fit reveal sliding distances, including hopping, close to what has been proposed in the past, i.e. ∼40 bp, but with an unexpectedly high 1D diffusion constant on non-specific DNA sequences. Including a mechanism of inter-segment transfer between distant DNA segments does not bring down the 1D diffusion to the expected fraction of the in vitro value. This suggests a mechanism where transcription factors can slide less hindered in vivo than what is given by a simple viscosity scaling argument or that a modification of the model is needed. For example, the estimated diffusion rate constant would be consistent with the expectation if parts of the chromosome, away from the operator site, were inaccessible for searching.

  • 127. Mahmutovic, Anel
    et al.
    Fange, David
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Berg, Otto G
    Elf, Johan
    Lost in presumption: stochastic reactions in spatial models2012Inngår i: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105Artikkel i tidsskrift (Fagfellevurdert)
  • 128. Malmqvist, Niklas
    Building a standard operating procedure for the analysis of mass spectrometry data2012Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    Mass spectrometry (MS) is used in peptidomics to find novel endogenous peptides that may lead to the discovery of new biomarkers. Identifying endogenous peptides from MS is a time-consuming and challenging task; storing identified peptides in a database and comparing them against unknown peptides from other MS runs avoids re-doing identification. MS produce large amounts of data, making interpretation difficult. A platform for helping the identification of endogenous peptides was developed in this project, including a library application for storing peptide data. Machine learning methods were also used to try to find patterns in peptide abundance that could be correlated to a specific sample or treatment type, which can help focus the identification work on peptides of high interest.

  • 129.
    Malmström, Lars
    et al.
    University of Zurich, S3IT.
    Bakochi, Anahita
    Lund University, Department of Clinical Sciences.
    Svensson, Gabriel
    Lund University, Department of Clinical Sciences.
    Kilsgård, Ola
    Lund University, Department of Clinical Sciences.
    Lantz, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Petersson, Ann Cathrine
    Region Skåne, Department of Clinical Microbiology.
    Hauri, Simon
    Lund University, Department of Clinical Sciences.
    Karlsson, Christofer
    Lund University, Department of Clinical Sciences.
    Malmström, Johan
    Lund University, Department of Clinical Sciences.
    Quantitative proteogenomics of human pathogens using DIA-MS2015Inngår i: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 129, nr SI, s. 98-107Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The increasing number of bacterial genomes in combination with reproducible quantitative proteome measurements provides new opportunities to explore how genetic differences modulate proteome composition and virulence. It is challenging to combine genome and proteome data as the underlying genome influences the proteome. We present a strategy to facilitate the integration of genome data from several genetically similar bacterial strains with data-independent analysis mass spectrometry (DIA-MS) for rapid interrogation of the combined data sets. The strategy relies on the construction of a composite genome combining all genetic data in a compact format, which can accommodate the fusion with quantitative peptide and protein information determined via DIA-MS. We demonstrate the method by combining data sets from whole genome sequencing, shotgun MS and DIA-MS from 34 clinical isolates of Streptococcus pyogenes. The data structure allows for fast exploration of the data showing that undetected proteins are on average more amenable to amino acid substitution than expressed proteins. We identified several significantly differentially expressed proteins between invasive and non-invasive strains. The work underlines how integration of whole genome sequencing with accurately quantified proteomes can further advance the interpretation of the relationship between genomes, proteomes and virulence. This article is part of a Special Issue entitled: Computational Proteomics.

  • 130.
    Marklund, Erik G.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi. University of Oxford, Oxford, UK.
    Zhang, Yichen
    University of Massachusetts, Amherst, USA; Alorica Inc, Irvine, CA USA.
    Basha, Eman
    University of Massachusetts, Amherst, USA; Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ USA.
    Benesch, Justin L P
    University of Oxford, Oxford, UK.
    Vierling, Elizabeth
    University of Massachusetts, Amherst, USA.
    Structural and functional aspects of the interaction partners of the small heat-shock protein in Synechocystis2018Inngår i: Cell stress & chaperones (Print), ISSN 1355-8145, E-ISSN 1466-1268, Vol. 23, nr 4, s. 723-732Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The canonical function of small heat-shock proteins (sHSPs) is to interact with proteins destabilized under conditions of cellular stress. While the breadth of interactions made by many sHSPs is well-known, there is currently little knowledge about what structural features of the interactors form the basis for their recognition. Here, we have identified 83 in vivo interactors of the sole sHSP in the cyanobacterium Synechocystis sp. PCC 6803, HSP16.6, reflective of stable associations with soluble proteins made under heat-shock conditions. By performing bioinformatic analyses on these interactors, we identify primary and secondary structural elements that are enriched relative to expectations from the cyanobacterial genome. In addition, by examining the Synechocystis interactors and comparing them with those identified to bind sHSPs in other prokaryotes, we show that sHSPs associate with specific proteins and biological processes. Our data are therefore consistent with a picture of sHSPs being broadly specific molecular chaperones that act to protect multiple cellular pathways.

  • 131.
    Markstedt, Olof
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Kubernetes as an approach for solving bioinformatic problems.2017Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    The cluster orchestration tool Kubernetes enables easy deployment and

    reproducibility of life science research by utilizing the advantages

    of the container technology. The container technology allows for easy

    tool creation, sharing and runs on any Linux system once it has been

    built. The applicability of Kubernetes as an approach to run

    bioinformatic workflows was evaluated and resulted in some examples

    of how Kubernetes and containers could be used within the field of

    life science and how they should not be used. The resulting examples

    serves as proof of concepts and the general idea of how

    implementation is done. Kubernetes allows for easy resource

    management and includes automatic scheduling of workloads. It scales

    rapidly and has some interesting components that are beneficial when

    conducting life science research.

  • 132.
    Martinez Barrio, Alvaro
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Centrum för bioinformatik.
    Ekerljung, Marie
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences.
    Jern, Patric
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Benachenhou, Farid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk virologi.
    Sperber, Göran O
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Bongcam-Rudloff, Erik
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences.
    Blomberg, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk virologi.
    Andersson, Göran
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences.
    Data mining of the dog genome reveals novel Canine Endogenous Retroviruses(CfERVs)Manuskript (preprint) (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    Mining the dog genome for canine endogenous retroviruses (CfERV) using the program RetroTector© identified 407 CfERVs (0.15% of the total genome size). Phylogenetic analysis showed that the majority of these CfERVs belong to the gammaretroviridae (n=313) genus. In this group, we found 33 integrated CfERVs with similarity to the human HERV-Fc1. Eighteen of them had conserved open reading frames open and seven of the 18 were recent integrations (≤ 5% LTR divergence). Some of these CfERVs may have potential for active retrotransposition and could actively contribute to the plasticity of canine genomes. Similar to other vertebrates, betaretroviruses (n=28) was the second most common group. In addition, four spuma-like and four gypsy-like CfERVs were identified, the latter group being rare in vertebrate genomes. Moreover, we identified 55 CfERVs that could not be classified unambiguously to any known retroviral genera. The integration landscape shows that all dog chromosomes have CfERV integrations with non-uniform distribution both along and across chromosomes. Some regions were essentially devoid of CfERVs whereas other regions had large numbers. Notably, in a comparison between dog and human genomes, CfERV were approximately one fifth of the amount of HERVs found. Species-specific mechanisms for purging and protection against retroviral infections are suggested to act in the dog genome. The CfERV integration pattern showed that a substantial fraction of annotated genes were found within 100 kb distance from annotated proviruses. The majority of such integrations were placed in antisense orientation relative to the transcriptional direction of the neighboring chromosomal genes. In conclusion, our results from Canis familiaris genome analysis support the notion that different mammals may interact distinctively with endogenous retroviruses.

  • 133.
    Martinez Barrio, Alvaro
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Centrum för bioinformatik.
    Feifei, Xu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi, Molekylär evolution.
    Lagercrantz, Erik
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences.
    Bongcam-Rudloff, Erik
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences.
    GeneFinder: "in silico" positional cloning of trait genesManuskript (preprint) (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    Motivation: Positional cloning of trait genes is extremely laborious and the amount of information available on gene function in different organisms is increasing so rapidly that it is hard for a research group to collect all the relevant information from a number of data sources without performing a large number of manual and time consuming searches.

    Results: A web service application named GeneFinder was designed and implemented. It collects selected available information related to trait loci within a given chromosomal region that control a specific phenotype. The information contains details on gene function, disease conditions, tissue expression as well as predicted gene homologies in several other species. The information gathered is further ordered by a special-purpose ranking algorithm. A web interface to the GeneFinder web service was also developed where the results are presented in a ranked list easing its interpretation. We explain the design of the architecture, show how our web interface works, and finally test a candidate region.

    Availability: GeneFinder is publicly available and free to use. The web interface is available at http://www.genefinder.org/.

  • 134. Merckx, Vincent S. F. T.
    et al.
    Hendriks, Kasper P.
    Beentjes, Kevin K.
    Mennes, Constantijn B.
    Becking, Leontine E.
    Peijnenburg, Katja T. C. A.
    Afendy, Aqilah
    Arumugam, Nivaarani
    de Boer, Hugo
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    Biun, Alim
    Buang, Matsain M.
    Chen, Ping-Ping
    Chung, Arthur Y. C.
    Dow, Rory
    Feijen, Frida A. A.
    Feijen, Hans
    Soest, Cobi Feijen-van
    Geml, Jozsef
    Geurts, Rene
    Gravendeel, Barbara
    Hovenkamp, Peter
    Imbun, Paul
    Ipor, Isa
    Janssens, Steven B.
    Jocque, Merlijn
    Kappes, Heike
    Khoo, Eyen
    Koomen, Peter
    Lens, Frederic
    Majapun, Richard J.
    Morgado, Luis N.
    Neupane, Suman
    Nieser, Nico
    Pereira, Joan T.
    Rahman, Homathevi
    Sabran, Suzana
    Sawang, Anati
    Schwallier, Rachel M.
    Shim, Phyau-Soon
    Smit, Harry
    Sol, Nicolien
    Spait, Maipul
    Stech, Michael
    Stokvis, Frank
    Sugau, John B.
    Suleiman, Monica
    Sumail, Sukaibin
    Thomas, Daniel C.
    van Tol, Jan
    Tuh, Fred Y. Y.
    Yahya, Bakhtiar E.
    Nais, Jamili
    Repin, Rimi
    Lakim, Maklarin
    Schilthuizen, Menno
    Evolution of endemismon a young tropical mountain2015Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, nr 7565, s. 347-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tropical mountains are hot spots of biodiversity and endemism(1-3), but the evolutionary origins of their unique biotas are poorly understood(4). In varying degrees, local and regional extinction, long-distance colonization, and local recruitment may all contribute to the exceptional character of these communities(5). Also, it is debated whether mountain endemics mostly originate from local lowland taxa, or from lineages that reach the mountain by long-range dispersal from cool localities elsewhere(6). Here we investigate the evolutionary routes to endemism by sampling an entire tropical mountain biota on the 4,095-metre-high Mount Kinabalu in Sabah, East Malaysia. We discover that most of its unique biodiversity is younger than the mountain itself (6 million years), and comprises a mix of immigrant pre-adapted lineages and descendants from local lowland ancestors, although substantial shifts from lower to higher vegetation zones in this latter group were rare. These insights could improve forecasts of the likelihood of extinction and 'evolutionary rescue'(7) in montane biodiversity hot spots under climate change scenarios.

  • 135.
    Morrison, David A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi. Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Phylogenetic networks: a new form of multivariate data summary for data mining and exploratory data analysis2014Inngår i: Wiley Interdisciplinary Reviews: Data Mining and Knowledge Discovery, ISSN 1942-4795, Vol. 4, nr 4, s. 296-312Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Exploratory data analysis (EDA) involving both graphical displays and numerical summaries of data, is intended to evaluate the characteristics of the data as well as providing a form of data mining. For multivariate data, the best-known visual summaries include discriminant analysis, ordination, and clustering, particularly metric ordinations such as principal components analysis. However, these techniques have limiting mathematical assumptions that are not always realistic. Recently, network techniques have been developed in the biological field of phylogenetics that address some of these limitations. They are now widely used in biology under the name phylogenetic networks, but they are actually of general applicability to any multivariate dataset. Phylogenetic networks are fast and relatively easy to calculate, which makes them ideal as a tool for EDA. This review provides an overview of the field, with particular reference to the use of what are called splits graphs. There are several types of splits graph, which summarize the multivariate data in different ways. Example analyses are presented based on the neighbor-net graph, which seems to be the most generally useful of the available algorithms. This should encourage the more widespread use of these networks whenever a summary of a multivariate dataset is required.For further resources related to this article, please visit the WIREs website.Conflict of interest: The author has declared no conflicts of interest for this article.

  • 136.
    Nam, Kiwoong
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Ellegren, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Recombination drives vertebrate genome contraction2012Inngår i: PLOS Genetics, ISSN 1553-7390, Vol. 8, nr 5, s. e1002680-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Selective and/or neutral processes may govern variation in DNA content and, ultimately, genome size. The observation in several organisms of a negative correlation between recombination rate and intron size could be compatible with a neutral model in which recombination is mutagenic for length changes. We used whole-genome data on small insertions and deletions within transposable elements from chicken and zebra finch, to demonstrate clear links between recombination rate and a number of attributes of reduced DNA content. Recombination rate was negatively correlated with the length of introns, transposable elements and intergenic spacer, and the rate of short insertions. Importantly, it was positively correlated with gene density, the rate of short deletions, the deletion bias, and the net change in sequence length. All these observations point at a pattern of more condensed genome structure in regions of high recombination. Based on the observed rates of small insertions and deletions and assuming that these rates are representative for the whole genome, we estimate that the genome of the most recent common ancestor of birds and lizards have lost nearly 20% of its DNA content up till present. Expansion of transposable elements can counteract the effect of deletions in an equilibrium mutation model, however, since the activity of transposable elements has been low in the avian lineage, the deletion bias is likely to have had a significant effect on genome size evolution in dinosaurs and birds, contributing to the maintenance of a small genome. We also demonstrate that most of the observed correlations between recombination rate and genome contraction parameters are seen in the human genome, including for segregating indel polymorphisms. Our data are compatible with a neutral model in which recombination drive vertebrate genome size evolution and give no direct support for a role of natural selection in this process.

  • 137. Nelson, Ronald M.
    et al.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Pettersson, Mats E.
    Shen, Xia
    Crooks, Lucy
    Besnier, François
    Álvarez-Castro, José
    Rönnegård, Lars
    Ek, Weronica
    Sheng, Zheya
    Kierczak, Marcin
    Holmgren, Sverker
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Carlborg, Örjan
    Swedish University of Agricultural Sciences, Division of Computational Genetics.
    MAPfastR: Quantitative trait loci mapping in outbred line crosses2013Inngår i: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 3, s. 2147-2149Artikkel i tidsskrift (Fagfellevurdert)
  • 138.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Breakdown of methods for phasing and imputation in the presence of double genotype sharing2012Rapport (Annet vitenskapelig)
  • 139.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Breakdown of methods for phasing and imputation in the presence of double genotype sharing2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, s. e60354:1-5Artikkel i tidsskrift (Fagfellevurdert)
  • 140.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Inferring haplotypes and parental genotypes in larger full sib-ships and other pedigrees with missing or erroneous genotype data2012Rapport (Annet vitenskapelig)
  • 141.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Inferring haplotypes and parental genotypes in larger full sib-ships and other pedigrees with missing or erroneous genotype data2012Inngår i: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 13, s. 85:1-13Artikkel i tidsskrift (Fagfellevurdert)
  • 142.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Two Optimization Problems in Genetics: Multi-dimensional QTL Analysis and Haplotype Inference2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The existence of new technologies, implemented in efficient platforms and workflows has made massive genotyping available to all fields of biology and medicine. Genetic analyses are no longer dominated by experimental work in laboratories, but rather the interpretation of the resulting data. When billions of data points representing thousands of individuals are available, efficient computational tools are required. The focus of this thesis is on developing models, methods and implementations for such tools.

    The first theme of the thesis is multi-dimensional scans for quantitative trait loci (QTL) in experimental crosses. By mating individuals from different lines, it is possible to gather data that can be used to pinpoint the genetic variation that influences specific traits to specific genome loci. However, it is natural to expect multiple genes influencing a single trait to interact. The thesis discusses model structure and model selection, giving new insight regarding under what conditions orthogonal models can be devised. The thesis also presents a new optimization method for efficiently and accurately locating QTL, and performing the permuted data searches needed for significance testing. This method has been implemented in a software package that can seamlessly perform the searches on grid computing infrastructures.

    The other theme in the thesis is the development of adapted optimization schemes for using hidden Markov models in tracing allele inheritance pathways, and specifically inferring haplotypes. The advances presented form the basis for more accurate and non-biased line origin probabilities in experimental crosses, especially multi-generational ones. We show that the new tools are able to reconstruct haplotypes and even genotypes in founder individuals and offspring alike, based on only unordered offspring genotypes. The tools can also handle larger populations than competing methods, resolving inheritance pathways and phase in much larger and more complex populations. Finally, the methods presented are also applicable to datasets where individual relationships are not known, which is frequently the case in human genetics studies. One immediate application for this would be improved accuracy for imputation of SNP markers within genome-wide association studies (GWAS).

    Delarbeid
    1. Coherent estimates of genetic effects with missing information
    Åpne denne publikasjonen i ny fane eller vindu >>Coherent estimates of genetic effects with missing information
    2012 (engelsk)Inngår i: Open Journal of Genetics, ISSN 2162-4453, E-ISSN 2162-4461, Vol. 2, s. 31-38Artikkel i tidsskrift (Fagfellevurdert) Published
    Emneord
    genetic effects, missing genotypes, orthogonal estimation, QTL analysis
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-180915 (URN)10.4236/ojgen.2012.21003 (DOI)
    Prosjekter
    eSSENCE
    Tilgjengelig fra: 2012-03-02 Laget: 2012-09-12 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    2. Fast and accurate detection of multiple quantitative trait loci
    Åpne denne publikasjonen i ny fane eller vindu >>Fast and accurate detection of multiple quantitative trait loci
    2013 (engelsk)Inngår i: Journal of Computational Biology, ISSN 1066-5277, E-ISSN 1557-8666, Vol. 20, s. 687-702Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-180916 (URN)10.1089/cmb.2012.0242 (DOI)000323822000006 ()
    Prosjekter
    eSSENCE
    Tilgjengelig fra: 2013-08-06 Laget: 2012-09-13 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    3. A Grid-Enabled Problem Solving Environment for QTL Analysis in R
    Åpne denne publikasjonen i ny fane eller vindu >>A Grid-Enabled Problem Solving Environment for QTL Analysis in R
    Vise andre…
    2010 (engelsk)Inngår i: Proc. 2nd International Conference on Bioinformatics and Computational Biology, Cary, NC: ISCA , 2010, s. 202-209Konferansepaper, Publicerat paper (Fagfellevurdert)
    sted, utgiver, år, opplag, sider
    Cary, NC: ISCA, 2010
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-111594 (URN)978-1-880843-76-5 (ISBN)
    Prosjekter
    eSSENCE
    Tilgjengelig fra: 2010-01-12 Laget: 2009-12-17 Sist oppdatert: 2018-01-12bibliografisk kontrollert
    4. cnF2freq: Efficient determination of genotype and haplotype probabilities in outbred populations using Markov models
    Åpne denne publikasjonen i ny fane eller vindu >>cnF2freq: Efficient determination of genotype and haplotype probabilities in outbred populations using Markov models
    2009 (engelsk)Inngår i: Bioinformatics and Computational Biology, Berlin: Springer-Verlag , 2009, s. 307-319Konferansepaper, Publicerat paper (Fagfellevurdert)
    sted, utgiver, år, opplag, sider
    Berlin: Springer-Verlag, 2009
    Serie
    Lecture Notes in Computer Science ; 5462
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-103916 (URN)10.1007/978-3-642-00727-9_29 (DOI)000265785800029 ()978-3-642-00726-2 (ISBN)
    Tilgjengelig fra: 2009-05-25 Laget: 2009-05-25 Sist oppdatert: 2017-01-25bibliografisk kontrollert
    5. An improved method for estimating chromosomal line origin in QTL analysis of crosses between outbred lines
    Åpne denne publikasjonen i ny fane eller vindu >>An improved method for estimating chromosomal line origin in QTL analysis of crosses between outbred lines
    2011 (engelsk)Inngår i: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 1, s. 57-64Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-156197 (URN)10.1534/g3.111.000109 (DOI)000312405400007 ()
    Prosjekter
    eSSENCE
    Tilgjengelig fra: 2011-06-01 Laget: 2011-07-15 Sist oppdatert: 2017-12-08bibliografisk kontrollert
    6. MAPfastR: Quantitative trait loci mapping in outbred line crosses
    Åpne denne publikasjonen i ny fane eller vindu >>MAPfastR: Quantitative trait loci mapping in outbred line crosses
    Vise andre…
    2013 (engelsk)Inngår i: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 3, s. 2147-2149Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-180917 (URN)10.1534/g3.113.008623 (DOI)000328334500005 ()
    Prosjekter
    eSSENCE
    Tilgjengelig fra: 2013-10-11 Laget: 2012-09-13 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    7. Haplotype inference based on hidden Markov models in the QTL–MAS 2010 multigenerational dataset
    Åpne denne publikasjonen i ny fane eller vindu >>Haplotype inference based on hidden Markov models in the QTL–MAS 2010 multigenerational dataset
    2011 (engelsk)Inngår i: Proc. 14th European Workshop on QTL Mapping and Marker Assisted Selection, London: BioMed Central , 2011, s. S10:1-7Konferansepaper, Publicerat paper (Fagfellevurdert)
    sted, utgiver, år, opplag, sider
    London: BioMed Central, 2011
    Serie
    BMC Proceedings, ISSN 1753-6561 ; 5:3
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-153449 (URN)10.1186/1753-6561-5-S3-S10 (DOI)
    Prosjekter
    eSSENCE
    Tilgjengelig fra: 2010-05-17 Laget: 2011-05-12 Sist oppdatert: 2017-01-25bibliografisk kontrollert
    8. Inferring haplotypes and parental genotypes in larger full sib-ships and other pedigrees with missing or erroneous genotype data
    Åpne denne publikasjonen i ny fane eller vindu >>Inferring haplotypes and parental genotypes in larger full sib-ships and other pedigrees with missing or erroneous genotype data
    2012 (engelsk)Inngår i: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 13, s. 85:1-13Artikkel i tidsskrift (Fagfellevurdert) Published
    Emneord
    haplotyping, phasing, genotype inference, nuclear family data, hidden Markov models
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-182488 (URN)10.1186/1471-2156-13-85 (DOI)000314354600001 ()
    Prosjekter
    eSSENCE
    Tilgjengelig fra: 2012-10-10 Laget: 2012-10-10 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    9. Breakdown of methods for phasing and imputation in the presence of double genotype sharing
    Åpne denne publikasjonen i ny fane eller vindu >>Breakdown of methods for phasing and imputation in the presence of double genotype sharing
    2012 (engelsk)Rapport (Annet vitenskapelig)
    Serie
    Technical report / Department of Information Technology, Uppsala University, ISSN 1404-3203 ; 2012-027
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-181598 (URN)
    Prosjekter
    eSSENCE
    Tilgjengelig fra: 2012-09-25 Laget: 2012-09-26 Sist oppdatert: 2017-01-25bibliografisk kontrollert
  • 143.
    Nettelblad, Carl
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Carlborg, Örjan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Centrum för bioinformatik.
    Pino-Querido, Ania
    University of Santiago de Compostela, Department of Genetics.
    Álvarez-Castro, José M.
    University of Santiago de Compostela, Department of Genetics.
    Coherent estimates of genetic effects with missing information2012Inngår i: Open Journal of Genetics, ISSN 2162-4453, E-ISSN 2162-4461, Vol. 2, s. 31-38Artikkel i tidsskrift (Fagfellevurdert)
  • 144.
    Nettelblad, Carl
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Mahjani, Behrang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Holmgren, Sverker
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för beräkningsvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Fast and accurate detection of multiple quantitative trait loci2013Inngår i: Journal of Computational Biology, ISSN 1066-5277, E-ISSN 1557-8666, Vol. 20, s. 687-702Artikkel i tidsskrift (Fagfellevurdert)
  • 145. Nicolis, Stamatios C.
    et al.
    Deneubourg, Jean-Louis
    Emerging patterns and food recruitment in ants: an analytical study1999Inngår i: Journal of Theoretical Biology, Vol. 198, nr 4, s. 575-592Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A model of food recruitment by social insects accounting for the competition between trails in the presence of an arbitrary number of sources is developed and analysed in detail. Both the case of identical environmental characteristics and the case where one source and the corresponding trail are different from the others are considered. Different collective responses depending on the environmental conditions, and without change of individual behaviour, are shown to exist, associated with the possibility that the colony may be led to exploit one source or a group of sources preferentially. The full bifurcation diagram of steady-state solutions is constructed from which the dominant exploitation patterns are identified. The biological relevance of the results is discussed and suggestions are made for their experimental testing in connection with the recruitment behavior of species using trail recruitment. The same phenomenological model can be used for different trail-laying species since the predictions are generic and not restricted to a given species, except for the parameter values used. (C) 1999 Academic Press.

  • 146. Nilsson, Emil
    et al.
    Boström, Adrian
    Mwinyi, Jessica
    Schiöth, Helgi
    Sleep deprivation affects genome wide DNA methylation profiles and RNA expression.Manuskript (preprint) (Annet vitenskapelig)
  • 147.
    Nilsson, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Ernst, Barbara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Voisin, Sarah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Sällman Almén, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Benedict, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Mwinyi, Jessica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Schultes, Bernd
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Roux-En Y Gastric Bypass Surgery Induces Genome-Wide Promoter-Specific Changes in DNA Methylation in Whole Blood of Obese Patients2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 2, artikkel-id e0115186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context

    DNA methylation has been proposed to play a critical role in many cellular and biological processes.

    Objective

    To examine the influence of Roux-en-Y gastric bypass (RYGB) surgery on genome-wide promoter-specific DNA methylation in obese patients. Promoters are involved in the initiation and regulation of gene transcription.

    Methods

    Promoter-specific DNA methylation in whole blood was measured in 11 obese patients (presurgery BMI >35 kg/m2, 4 females), both before and 6 months after RYGB surgery, as well as once only in a control group of 16 normal-weight men. In addition, body weight and fasting plasma glucose were measured after an overnight fast.

    Results

    The mean genome-wide distance between promoter-specific DNA methylation of obese patients at six months after RYGB surgery and controls was shorter, as compared to that at baseline (p<0.001). Moreover, postsurgically, the DNA methylation of 51 promoters was significantly different from corresponding values that had been measured at baseline (28 upregulated and 23 downregulated, P<0.05 for all promoters, Bonferroni corrected). Among these promoters, an enrichment for genes involved in metabolic processes was found (n = 36, P<0.05). In addition, the mean DNA methylation of these 51 promoters was more similar after surgery to that of controls, than it had been at baseline (P<0.0001). When controlling for the RYGB surgery-induced drop in weight (-24% of respective baseline value) and fasting plasma glucose concentration (-16% of respective baseline value), the DNA methylation of only one out of 51 promoters (~2%) remained significantly different between the pre-and postsurgery time points.

    Conclusions

    Epigenetic modifications are proposed to play an important role in the development of and predisposition to metabolic diseases, including type II diabetes and obesity. Thus, our findings may form the basis for further investigations to unravel the molecular effects of gastric bypass surgery.

    Clinical Trial

    ClinicalTrials.gov NCT01730742

  • 148.
    Nilsson, R. Henrik
    et al.
    University of Gothenburg, Department of Biological and Environmental Sciences; Gothenburg Global Biodiversity Centre.
    Sánchez-García, Marisol
    Clark University, Department of Biology.
    Ryberg, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi. University of Tennessee.
    Abarenkov, Kessy
    University of Tartu, Natural History Museum.
    Wurzbacher, Christian
    University of Gothenburg, Department of Biological and Environmental Sciences; Gothenburg Global Biodiversity Centre.
    Kristiansson, Erik
    Chalmers University of Technology, Department of Mathematical Statistics.
    Read quality-based trimming of the distal ends of public fungal DNA sequences is nowhere near satisfactory2017Inngår i: MycoKeys, ISSN 1314-4057, E-ISSN 1314-4049, Vol. 26, s. 13-24Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    DNA sequences are increasingly used for taxonomic and functional assessment of environmental communities. In mycology, the nuclear ribosomal internal transcribed spacer (ITS) region is the most commonly chosen marker for such pursuits. Molecular identification is associated with many challenges, one of which is low read quality of the reference sequences used for inference of taxonomic and functional properties of the newly sequenced community (or single taxon). This study investigates whether public fungal ITS sequences are subjected to sufficient trimming in their distal (5’ and 3’) ends prior to deposition in the public repositories. We examined 86 species (and 10,584 sequences) across the fungal tree of life, and we found that on average 13.1% of the sequences were poorly trimmed in one or both of their 5’ and 3’ ends. Deposition of poorly trimmed entries was found to continue through 2016. Poorly trimmed reference sequences add noise and mask biological signal in sequence similarity searches and phylogenetic analyses, and we provide a set of recommendations on how to manage the sequence trimming problem.

  • 149. Nilsson, R. Henrik
    et al.
    Tedersoo, Leho
    Abarenkov, Kessy
    Ryberg, Martin
    Kristiansson, Erik
    Hartmann, Martin
    Schoch, Conrad L.
    Nylander, Johan A. A.
    Bergsten, Johannes
    Porter, Teresita M.
    Five simple guidelines for establishing basic authenticity and reliability of newly generated fungal ITS sequences.2012Annet (Annet vitenskapelig)
  • 150.
    Nordesjö, Olle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Searching for novel protein-protein specificities using a combined approach of sequence co-evolution and local structural equilibration2016Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Greater understanding of how we can use protein simulations and statistical characteristics of biomolecular interfaces as proxies for biological function will make manifest major advances in protein engineering. Here we show how to use calculated change in binding affinity and coevolutionary scores to predict the functional effect of mutations in the interface between a Histidine Kinase and a Response Regulator. These proteins participate in the Two-Component Regulatory system, a system for intracellular signalling found in bacteria. We find that both scores work as proxies for functional mutants and demonstrate a ~30 fold improvement in initial positive predictive value compared with choosing randomly from a sequence space of 160 000 variants in the top 20 mutants. We also demonstrate qualitative differences in the predictions of the two scores, primarily a tendency for the coevolutionary score to miss out on one class of functional mutants with enriched frequency of the amino acid threonine in one position. 

12345 101 - 150 of 241
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