Endre søk
Begrens søket
1 - 44 of 44
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Akhter, Shirin
    et al.
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Kretzschmar, Warren W.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nordal, Veronika
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Delhomme, Nicolas
    Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Street, Nathaniel R.
    Umea Sweden, Dept Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Nilsson, Ove
    Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Emanuelsson, Olof
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sundström, Jens F.
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Integrative Analysis of Three RNA Sequencing Methods Identifies Mutually Exclusive Exons of MADS-Box Isoforms During Early Bud Development in Picea abies2018Inngår i: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 9, artikkel-id 1625Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent efforts to sequence the genomes and transcriptomes of several gymnosperm species have revealed an increased complexity in certain gene families in gymnosperms as compared to angiosperms. One example of this is the gymnosperm sister Glade to angiosperm TM3-like MADS-box genes, which at least in the conifer lineage has expanded in number of genes. We have previously identified a member of this subclade, the conifer gene DEFICIENS AGAMOUS LIKE 19 (DAL19), as being specifically upregulated in cone-setting shoots. Here, we show through Sanger sequencing of mRNA-derived cDNA and mapping to assembled conifer genomic sequences that DAL19 produces six mature mRNA splice variants in Picea abies. These splice variants use alternate first and last exons, while their four central exons constitute a core region present in all six transcripts. Thus, they are likely to be transcript isoforms. Quantitative Real-Time PCR revealed that two mutually exclusive first DAL19 exons are differentially expressed across meristems that will form either male or female cones, or vegetative shoots. Furthermore, mRNA in situ hybridization revealed that two mutually exclusive last DAL19 exons were expressed in a cell-specific pattern within bud meristems. Based on these findings in DAL19, we developed a sensitive approach to transcript isoform assembly from short-read sequencing of mRNA. We applied this method to 42 putative MADS-box core regions in P abies, from which we assembled 1084 putative transcripts. We manually curated these transcripts to arrive at 933 assembled transcript isoforms of 38 putative MADS-box genes. 152 of these isoforms, which we assign to 28 putative MADS-box genes, were differentially expressed across eight female, male, and vegetative buds. We further provide evidence of the expression of 16 out of the 38 putative MADS-box genes by mapping PacBio Iso-Seq circular consensus reads derived from pooled sample sequencing to assembled transcripts. In summary, our analyses reveal the use of mutually exclusive exons of MADS-box gene isoforms during early bud development in P. abies, and we find that the large number of identified MADS-box transcripts in P. abies results not only from expansion of the gene family through gene duplication events but also from the generation of numerous splice variants.

  • 2.
    Alneberg, Johannes
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bioinformatic Methods in Metagenomics2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Microbial organisms are a vital part of our global ecosystem. Yet, our knowledge of them is still lacking. Direct sequencing of microbial communities, i.e. metagenomics, have enabled detailed studies of these microscopic organisms by inspection of their DNA sequences without the need to culture them. Furthermore, the development of modern high- throughput sequencing technologies have made this approach more powerful and cost-effective. Taken together, this has shifted the field of microbiology from previously being centered around microscopy and culturing studies, to largely consist of computational analyses of DNA sequences. One such computational analysis which is the main focus of this thesis, aims at reconstruction of the complete DNA sequence of an organism, i.e. its genome, directly from short metagenomic sequences.

    This thesis consists of an introduction to the subject followed by five papers. Paper I describes a large metagenomic data resource spanning the Baltic Sea microbial communities. This dataset is complemented with a web-interface allowing researchers to easily extract and visualize detailed information. Paper II introduces a bioinformatic method which is able to reconstruct genomes from metagenomic data. This method, which is termed CONCOCT, is applied on Baltic Sea metagenomics data in Paper III and Paper V. This enabled the reconstruction of a large number of genomes. Analysis of these genomes in Paper III led to the proposal of, and evidence for, a global brackish microbiome. Paper IV presents a comparison between genomes reconstructed from metagenomes with single-cell sequenced genomes. This further validated the technique presented in Paper II as it was found to produce larger and more complete genomes than single-cell sequencing.

  • 3.
    Alneberg, Johannes
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Bennke, Christin
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Beier, Sara
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Pinhassi, Jarone
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Jürgens, Klaus
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Ekman, Martin
    Department of Ecology, Environment and Plant Sciences, Stockholm University Science for Life Laboratory, Solna, Sweden.
    Ininbergs, Karolina
    Department of Ecology, Environment and Plant Sciences, Stockholm University Science for Life Laboratory, Solna, Sweden.
    Labrenz, Matthias
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Andersson, Anders F.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Recovering 2,032 Baltic Sea microbial genomes by optimized metagenomic binningManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Aquatic microorganism are key drivers of global biogeochemical cycles and form the basis of aquatic food webs. However, there is still much left to be learned about these organisms and their interaction within specific environments, such as the Baltic Sea. Crucial information for such an understanding can be found within the genome sequences of organisms within the microbial community.

    In this study, the previous set of Baltic Sea clusters, constructed by Hugert et al., is greatly expanded using a large set of metagenomic samples, spanning the environmental gradients of the Baltic Sea. In total, 124 samples were individually assembled and binned to obtain 2,032 Metagenome Assembled Genomes (MAGs), clustered into 353 prokaryotic and 14 eukaryotic species- level clusters. The prokaryotic genomes were widely distributed over the prokaryotic tree of life, representing 20 different phyla, while the eukaryotic genomes were mostly limited to the division of Chlorophyta. The large number of reconstructed genomes allowed us to identify key factors determining the quality of the genome reconstructions.

    The Baltic Sea is heavily influenced of human activities of which we might not see the full implications. The genomes reported within this study will greatly aid further studies in our strive for an understanding of the Baltic Sea microbial ecosystem.

  • 4.
    Alneberg, Johannes
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Karlsson, Christofer M. G.
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden..
    Divne, Anna-Maria
    Uppsala Univ, Dept Cell & Mol Biol, SciLifeLab, Uppsala, Sweden..
    Bergin, Claudia
    Uppsala Univ, Dept Cell & Mol Biol, SciLifeLab, Uppsala, Sweden..
    Homa, Felix
    Uppsala Univ, Dept Cell & Mol Biol, SciLifeLab, Uppsala, Sweden..
    Lindh, Markus V.
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden.;Lund Univ, Dept Biol, Lund, Sweden..
    Hugerth, Luisa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ettema, Thijs J. G.
    Uppsala Univ, Dept Cell & Mol Biol, SciLifeLab, Uppsala, Sweden..
    Bertilsson, Stefan
    Uppsala Univ, Dept Ecol & Genet, Sci Life Lab, Limnol, Uppsala, Sweden..
    Andersson, Anders F.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pinhassi, Jarone
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden..
    Genomes from uncultivated prokaryotes: a comparison of metagenome-assembled and single-amplified genomes2018Inngår i: Microbiome, ISSN 0026-2633, E-ISSN 2049-2618, Vol. 6, artikkel-id 173Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Prokaryotes dominate the biosphere and regulate biogeochemical processes essential to all life. Yet, our knowledge about their biology is for the most part limited to the minority that has been successfully cultured. Molecular techniques now allow for obtaining genome sequences of uncultivated prokaryotic taxa, facilitating in-depth analyses that may ultimately improve our understanding of these key organisms. Results: We compared results from two culture-independent strategies for recovering bacterial genomes: single-amplified genomes and metagenome-assembled genomes. Single-amplified genomes were obtained from samples collected at an offshore station in the Baltic Sea Proper and compared to previously obtained metagenome-assembled genomes from a time series at the same station. Among 16 single-amplified genomes analyzed, seven were found to match metagenome-assembled genomes, affiliated with a diverse set of taxa. Notably, genome pairs between the two approaches were nearly identical (average 99.51% sequence identity; range 98.77-99.84%) across overlapping regions (30-80% of each genome). Within matching pairs, the single-amplified genomes were consistently smaller and less complete, whereas the genetic functional profiles were maintained. For the metagenome-assembled genomes, only on average 3.6% of the bases were estimated to be missing from the genomes due to wrongly binned contigs. Conclusions: The strong agreement between the single-amplified and metagenome-assembled genomes emphasizes that both methods generate accurate genome information from uncultivated bacteria. Importantly, this implies that the research questions and the available resources are allowed to determine the selection of genomics approach for microbiome studies.

  • 5.
    Alneberg, Johannes
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Karlsson, Christofer M.G.
    Centre for Ecology and Evolution in Microbial Model Systems, EEMiS, Linnaeus University, Barlastgatan 11, 391 82 Kalmar, Sweden.
    Divne, Anna-Maria
    Department of Cell and Molecular Biology, SciLifeLab, Uppsala University, Uppsala, Sweden .
    Bergin, Claudia
    Department of Cell and Molecular Biology, SciLifeLab, Uppsala University, Uppsala, Sweden .
    Homa, Felix
    Department of Cell and Molecular Biology, SciLifeLab, Uppsala University, Uppsala, Sweden .
    Lindh, Markus V.
    Centre for Ecology and Evolution in Microbial Model Systems, EEMiS, Linnaeus University, Barlastgatan 11, 391 82 Kalmar, Sweden.
    Hugerth, Luisa W.
    Karolinska Institutet, Science for Life Laboratory, Department of Molecular, Tumour and Cell Biology, Centre for Translational Microbiome Research, Solna, Sweden.
    Ettema, Thijs JG
    Department of Cell and Molecular Biology, SciLifeLab, Uppsala University, Uppsala, Sweden.
    Bertilsson, Stefan
    Department of Ecology and Genetics, Limnology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Andersson, Anders F.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Pinhassi, Jarone
    Centre for Ecology and Evolution in Microbial Model Systems, EEMiS, Linnaeus University, Barlastgatan 11, 391 82 Kalmar, Sweden.
    Genomes from uncultivated prokaryotes: a comparison of metagenome-assembled and single-amplified genomesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: Prokaryotes dominate the biosphere and regulate biogeochemical processes essential to all life. Yet, our knowledge about their biology is for the most part limited to the minority that has been successfully cultured. Molecular techniques now allow for obtaining genome sequences of uncultivated prokaryotic taxa, facilitating in-depth analyses that may ultimately improve our understanding of these key organisms.

    Results: We compared results from two culture-independent strategies for recovering bacterial genomes: single-amplified genomes and metagenome-assembled genomes. Single-amplified genomes were obtained from samples collected at an offshore station in the Baltic Sea Proper and compared to previously obtained metagenome-assembled genomes from a time series at the same station. Among 16 single-amplified genomes analyzed, seven were found to match metagenome-assembled genomes, affiliated with a diverse set of taxa. Notably, genome pairs between the two approaches were nearly identical (>98.7% identity) across overlapping regions (30-80% of each genome). Within matching pairs, the single-amplified genomes were consistently smaller and less complete, whereas the genetic functional profiles were maintained. For the metagenome-assembled genomes, only on average 3.6% of the bases were estimated to be missing from the genomes due to wrongly binned contigs; the metagenome assembly was found to cause incompleteness to a higher degree than the binning procedure.

    Conclusions: The strong agreement between the single-amplified and metagenome-assembled genomes emphasizes that both methods generate accurate genome information from uncultivated bacteria. Importantly, this implies that the research questions and the available resources are allowed to determine the selection of genomics approach for microbiome studies.

  • 6.
    Alneberg, Johannes
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sundh, John
    Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.
    Bennke, Christin
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Beier, Sara
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Lundin, Daniel
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Hugerth, Luisa
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Pinhassi, Jarone
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Kisand, Veljo
    University of Tartu, Institute of Technology, Tartu, Estonia.
    Riemann, Lasse
    Section for Marine Biological Section, Department of Biology, University of Copenhagen, Helsingør, Denmark.
    Jürgens, Klaus
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Labrenz, Matthias
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Andersson, Anders F.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    BARM and BalticMicrobeDB, a reference metagenome and interface to meta-omic data for the Baltic SeaManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The Baltic Sea is one of the world’s largest brackish water bodies and is characterised by pronounced physicochemical gradients where microbes are the main biogeochemical catalysts. Meta-omic methods provide rich information on the composition of, and activities within microbial ecosystems, but are computationally heavy to perform. We here present the BAltic Sea Reference Metagenome (BARM), complete with annotated genes to facilitate further studies with much less computational effort. The assembly is constructed using 2.6 billion metagenomic reads from 81 water samples, spanning both spatial and temporal dimensions, and contains 6.8 million genes that have been annotated for function and taxonomy. The assembly is useful as a reference, facilitating taxonomic and functional annotation of additional samples by simply mapping their reads against the assembly. This capability is demonstrated by the successful mapping and annotation of 24 external samples. In addition, we present a public web interface, BalticMicrobeDB, for interactive exploratory analysis of the dataset.

  • 7.
    Alneberg, Johannes
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sundh, John
    Stockholm Univ, Sci Life Lab, Dept Biochem & Biophys, S-17165 Solna, Sweden..
    Bennke, Christin
    Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany..
    Beier, Sara
    Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany..
    Lundin, Daniel
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, S-39182 Kalmar, Sweden..
    Hugerth, Luisa W.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Mol Tumor & Cell Biol, Ctr Translat Microbiome Res, Sci Life Lab, S-17165 Solna, Sweden..
    Pinhassi, Jarone
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, S-39182 Kalmar, Sweden..
    Kisand, Veljo
    Univ Tartu, Inst Technol, EE-50411 Tartu, Estonia..
    Riemann, Lasse
    Univ Copenhagen, Sect Marine Biol Sect, Dept Biol, DK-3000 Helsingor, Denmark..
    Juergens, Klaus
    Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany..
    Labrenz, Matthias
    Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany..
    Andersson, Anders F.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    BARM and BalticMicrobeDB, a reference metagenome and interface to meta-omic data for the Baltic Sea2018Inngår i: Scientific Data, E-ISSN 2052-4463, Vol. 5, artikkel-id 180146Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Baltic Sea is one of the world's largest brackish water bodies and is characterised by pronounced physicochemical gradients where microbes are the main biogeochemical catalysts. Meta-omic methods provide rich information on the composition of, and activities within, microbial ecosystems, but are computationally heavy to perform. We here present the Baltic Sea Reference Metagenome (BARM), complete with annotated genes to facilitate further studies with much less computational effort. The assembly is constructed using 2.6 billion metagenomic reads from 81 water samples, spanning both spatial and temporal dimensions, and contains 6.8 million genes that have been annotated for function and taxonomy. The assembly is useful as a reference, facilitating taxonomic and functional annotation of additional samples by simply mapping their reads against the assembly. This capability is demonstrated by the successful mapping and annotation of 24 external samples. In addition, we present a public web interface, BalticMicrobeDB, for interactive exploratory analysis of the dataset.

  • 8.
    Asp, Michaela
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Spatially Resolved Gene Expression Analysis2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Spatially resolved transcriptomics has greatly expanded our knowledge of complex multicellular biological systems. To date, several technologies have been developed that combine gene expression data with information about its spatial tissue context. There is as yet no single spatial method superior to all others, and the existing methods have jointly contributed to progress in this field of technology. Some challenges presented by existing protocols include having a limited number of targets, being labor extensive, being tissue-type dependent and having low throughput or limited resolution. Within the scope of this thesis, many aspects of these challenges have been taken into consideration, resulting in a detailed evaluation of a recently developed spatial transcriptome-wide method. This method, termed Spatial Transcriptomics (ST), enables the spatial location of gene activity to be preserved and visually links it to its histological position and anatomical context. Paper I describes all the details of the experimental protocol, which starts when intact tissue sections are placed on barcoded microarrays and finishes with high throughput sequencing. Here, spatially resolved transcriptome-wide data are obtained from both mouse olfactory bulb and breast cancer samples, demonstrating the broad tissue applicability and robustness of the approach. In Paper II, the ST technology is applied to samples of human adult heart, a tissue type that contains large proportions of fibrous tissue and thus makes RNA extraction substantially more challenging. New protocol strategies are optimized in order to generate spatially resolved transcriptome data from heart failure patients. This demonstrates the advantage of using the technology for the identification of lowly expressed biomarkers that have previously been seen to correlate with disease progression in patients suffering heart failure. Paper III shows that, although the ST technology has limited resolution compared to other techniques, it can be combined with single-cell RNA-sequencing and hence allow the spatial positions of individual cells to be recovered. The combined approach is applied to developing human heart tissue and reveals cellular heterogeneity of distinct compartments within the complete organ. Since the ST technology is based on the sequencing of mRNA tags, Paper IV describes a new version of the method, in which spatially resolved analysis of full-length transcripts is being developed. Exploring the spatial distribution of full-length transcripts in tissues enables further insights into alternative splicing and fusion transcripts and possible discoveries of new genes.  

  • 9.
    Asp, Michaela
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Borgström, Erik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Stuckey, Alexander
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Gruselius, Joel
    Carlberg, Konstantin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Andrusivova, Zaneta
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Salmén, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Käller, Max
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ståhl, Patrik
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Spatial Isoform Profiling within Individual Tissue SectionsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Spatial Transcriptomics has been shown to be a persuasive RNA sequencing

    technology for analyzing cellular heterogeneity within tissue sections. The

    technology efficiently captures and barcodes 3’ tags of all polyadenylated

    transcripts from a tissue section, and thus provides a powerful platform when

    performing quantitative spatial gene expression studies. However, the current

    protocol does not recover the full-length information of transcripts, and

    consequently lack information regarding alternative splice variants. Here, we

    introduce a novel protocol for spatial isoform profiling, using Spatial

    Transcriptomics barcoded arrays.

  • 10.
    Asp, Michaela
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Giacomello, Stefania
    Fürth, Daniel
    Reimegård, Johan
    Wärdell, Eva
    Custodio, Joaquin
    Salmén, Fredrik
    Sundström, Erik
    Åkesson, Elisabet
    Bienko, Magda
    Månsson‐Broberg, Agneta
    Ståhl, Patrik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Sylvén, Christer
    Lundeberg, Joakim
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    An organ‐wide gene expression atlas of the developing human heartManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The human developing heart holds a greater proportion of stem-cell-like cells than the adult heart. However, it is not completely understood how these stem cells differentiate into various cardiac cell types. We have performed an organ-wide transcriptional landscape analysis of the developing heart to advance our understanding of cardiac morphogenesis in humans. Comprehensive spatial gene expression analyses identified distinct profiles that correspond not only to individual chamber compartments, but also distinctive regions within the outflow tract. Furthermore, the generated spatial expression reference maps facilitated the assignment of 3,787 human embryonic cardiac cells obtained from single-cell RNA-sequencing to an in situlocation. Through this approach we reveal that the outflow tract contains a wider range of cell types than the chambers, and that the epicardium expression profile can be traced to several cell types that are activated at different stages of development. We also provide a 3D spatial model of human embryonic cardiac cells to enable further studies of the developing human heart. 

  • 11. Bell, E.
    et al.
    Lamminmäki, T.
    Alneberg, Johannes
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Andersson, Anders F.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Qian, C.
    Xiong, W.
    Hettich, R. L.
    Balmer, L.
    Frutschi, M.
    Sommer, G.
    Bernier-Latmani, R.
    Biogeochemical cycling by a low-diversity microbial community in deep groundwater2018Inngår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 9, nr SEP, artikkel-id 2129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Olkiluoto, an island on the south-west coast of Finland, will host a deep geological repository for the storage of spent nuclear fuel. Microbially induced corrosion from the generation of sulphide is therefore a concern as it could potentially compromise the longevity of the copper waste canisters. Groundwater at Olkiluoto is geochemically stratified with depth and elevated concentrations of sulphide are observed when sulphate-rich and methane-rich groundwaters mix. Particularly high sulphide is observed in methane-rich groundwater from a fracture at 530.6 mbsl, where mixing with sulphate-rich groundwater occurred as the result of an open drill hole connecting two different fractures at different depths. To determine the electron donors fuelling sulphidogenesis, we combined geochemical, isotopic, metagenomic and metaproteomic analyses. This revealed a low diversity microbial community fuelled by hydrogen and organic carbon. Sulphur and carbon isotopes of sulphate and dissolved inorganic carbon, respectively, confirmed that sulphate reduction was ongoing and that CO2 came from the degradation of organic matter. The results demonstrate the impact of introducing sulphate to a methane-rich groundwater with limited electron acceptors and provide insight into extant metabolisms in the terrestrial subsurface. 

  • 12.
    Berglund, Emelie
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Maaskola, Jonas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Schultz, Niklas
    Friedrich, Stefanie
    Marklund, Maja
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Bergenstrahle, Joseph
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Tarish, Firas
    Tanoglidi, Anna
    Vickovic, Sanja
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Larsson, Ludvig
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Salmén, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ogris, Christoph
    Wallenborg, Karolina
    Lagergren, Jens
    KTH, Skolan för elektroteknik och datavetenskap (EECS), Beräkningsvetenskap och beräkningsteknik (CST).
    Ståhl, Patrik
    Sonnhammer, Erik
    Helleday, Thomas
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity2018Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, artikkel-id 2419Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.

  • 13.
    Cavalli, Marco
    et al.
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Baltzer, Nicholas
    Uppsala Univ, Dept Cell & Mol Biol Computat Biol & Bioinformat, Uppsala, Sweden..
    Umer, Husen M.
    Uppsala Univ, Dept Cell & Mol Biol Computat Biol & Bioinformat, Uppsala, Sweden..
    Grau, Jan
    Martin Luther Univ Halle Wittenberg, Inst Comp Sci, Halle, Germany..
    Lemnian, Ioana
    Martin Luther Univ Halle Wittenberg, Inst Comp Sci, Halle, Germany..
    Pan, Gang
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Wallerman, Ola
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Spalinskas, Rapolas
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Sahlén, Pelin
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Grosse, Ivo
    Martin Luther Univ Halle Wittenberg, Inst Comp Sci, Halle, Germany.;German Ctr Integrat Biodivers Res iDiv, Leipzig, Germany..
    Komorowski, Jan
    Uppsala Univ, Dept Cell & Mol Biol Computat Biol & Bioinformat, Uppsala, Sweden.;Polish Acad Sci, Inst Comp Sci, Warsaw, Poland..
    Wadelius, Claes
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Allele specific chromatin signals, 3D interactions, and motif predictions for immune and B cell related diseases2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 2695Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several Genome Wide Association Studies (GWAS) have reported variants associated to immune diseases. However, the identified variants are rarely the drivers of the associations and the molecular mechanisms behind the genetic contributions remain poorly understood. ChIP-seq data for TFs and histone modifications provide snapshots of protein-DNA interactions allowing the identification of heterozygous SNPs showing significant allele specific signals (AS-SNPs). AS-SNPs can change a TF binding site resulting in altered gene regulation and are primary candidates to explain associations observed in GWAS and expression studies. We identified 17,293 unique AS-SNPs across 7 lymphoblastoid cell lines. In this set of cell lines we interrogated 85% of common genetic variants in the population for potential regulatory effect and we identified 237 AS-SNPs associated to immune GWAS traits and 714 to gene expression in B cells. To elucidate possible regulatory mechanisms we integrated long-range 3D interactions data to identify putative target genes and motif predictions to identify TFs whose binding may be affected by AS-SNPs yielding a collection of 173 AS-SNPs associated to gene expression and 60 to B cell related traits. We present a systems strategy to find functional gene regulatory variants, the TFs that bind differentially between alleles and novel strategies to detect the regulated genes.

  • 14.
    Das, Sarbashis
    et al.
    Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, S-75124 Uppsala, Sweden..
    Frisk, Christoffer
    Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, S-75124 Uppsala, Sweden..
    Eriksson, Maria J.
    Karolinska Univ Hosp, Dept Clin Physiol, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden..
    Walentinsson, Anna
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab Dis, S-43183 Gothenburg, Sweden..
    Corbascio, Matthias
    Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Thorac Surg, S-17176 Stockholm, Sweden..
    Hage, Camilla
    Karolinska Inst, Dept Med, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Heart & VascularTheme, S-17176 Stockholm, Sweden..
    Kumar, Chanchal
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab Dis, S-43183 Gothenburg, Sweden.;Karolinska Inst, ICMC, Dept Med, S-14157 Huddinge, Sweden..
    Asp, Michaela
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Maret, Eva
    Karolinska Univ Hosp, Dept Clin Physiol, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden..
    Persson, Hans
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, S-18288 Stockholm, Sweden.;Danderyd Hosp, Dept Cardiol, S-18288 Stockholm, Sweden..
    Linde, Cecilia
    Karolinska Inst, Dept Med, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Heart & VascularTheme, S-17176 Stockholm, Sweden..
    Persson, Bengt
    Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, S-75124 Uppsala, Sweden.;Karolinska Inst, Dept Med Biochem & Biophys, Sci Life Lab, S-17177 Stockholm, Sweden..
    Transcriptomics of cardiac biopsies reveals differences in patients with or without diagnostic parameters for heart failure with preserved ejection fraction2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 3179Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heart failure affects 2-3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics would show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction >= 45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group.

  • 15.
    Einarsdottir, T.
    et al.
    Inst Expt Pathol Keldur, Keldnavegur 3, IS-112 Reykjavik, Iceland..
    Sigurdardottir, H.
    Inst Expt Pathol Keldur, Keldnavegur 3, IS-112 Reykjavik, Iceland..
    Einarsdottir, Elisabet
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bjornsdottir, T. S.
    Inst Expt Pathol Keldur, Keldnavegur 3, IS-112 Reykjavik, Iceland..
    Moritella viscosa in lumpfish (Cyclopterus lumpus) and Atlantic salmon (Salmo salar)2019Inngår i: Fish and Shellfish Immunology, ISSN 1050-4648, E-ISSN 1095-9947, Vol. 91, s. 469-469Artikkel i tidsskrift (Annet vitenskapelig)
  • 16. Eisfeldt, J.
    et al.
    Pettersson, M.
    Vezzi, F.
    Wincent, J.
    Käller, Max
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Gruselius, J.
    Nilsson, D.
    Syk Lundberg, E.
    Carvalho, C. M. B.
    Lindstrand, A.
    Comprehensive structural variation genome map of individuals carrying complex chromosomal rearrangements2019Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 15, nr 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Complex chromosomal rearrangements (CCRs) are rearrangements involving more than two chromosomes or more than two breakpoints. Whole genome sequencing (WGS) allows for outstanding high resolution characterization on the nucleotide level in unique sequences of such rearrangements, but problems remain for mapping breakpoints in repetitive regions of the genome, which are known to be prone to rearrangements. Hence, multiple complementary WGS experiments are sometimes needed to solve the structures of CCRs. We have studied three individuals with CCRs: Case 1 and Case 2 presented with de novo karyotypically balanced, complex interchromosomal rearrangements (46,XX,t(2;8;15)(q35;q24.1;q22) and 46,XY,t(1;10;5)(q32;p12;q31)), and Case 3 presented with a de novo, extremely complex intrachromosomal rearrangement on chromosome 1. Molecular cytogenetic investigation revealed cryptic deletions in the breakpoints of chromosome 2 and 8 in Case 1, and on chromosome 10 in Case 2, explaining their clinical symptoms. In Case 3, 26 breakpoints were identified using WGS, disrupting five known disease genes. All rearrangements were subsequently analyzed using optical maps, linked-read WGS, and short-read WGS. In conclusion, we present a case series of three unique de novo CCRs where we by combining the results from the different technologies fully solved the structure of each rearrangement. The power in combining short-read WGS with long-molecule sequencing or optical mapping in these unique de novo CCRs in a clinical setting is demonstrated.

  • 17.
    Fernandez Navarro, Jose
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ståhl, Patrik L.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    ST viewer: a tool for analysis and visualization of spatial transcriptomics datasets2019Inngår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 35, nr 6, s. 1058-1060Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Motivation Spatial Transcriptomics (ST) is a technique that combines high-resolution imaging with spatially resolved transcriptome-wide sequencing. This novel type of data opens up many possibilities for analysis and visualization, most of which are either not available with standard tools or too complex for normal users. Results Here, we present a tool, ST Viewer, which allows real-time interaction, analysis and visualization of Spatial Transcriptomics datasets through a seamless and smooth user interface. Availability and implementation The ST Viewer is open source under a MIT license and it is available at https://github.com/SpatialTranscriptomicsResearch/st_viewer. Supplementary information Supplementary data are available at Bioinformatics online.

  • 18.
    Giacomello, Stefania
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Stockholm, Sweden..
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Preparation of plant tissue to enable Spatial Transcriptomics profiling using barcoded microarrays2018Inngår i: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 13, nr 11, s. 2425-2446Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Elucidation of the complex processes involved in plant growth requires analysis of the spatial gene expression patterns in all affected tissues. This protocol extension is an adaptation of a protocol that describes how to use barcoded oligo-dT microarrays to evaluate spatial global gene expression profiles in mammalian tissue to enable it to be applied to plant material. Here, we explain the required adjustments for preparing and treating plant tissue sections on the array surface, specifically in regard to how to permeabilize and remove the tissue. Once the tissue has been removed, the cDNA-mRNA hybrid that is left on the slide is processed in the same way as cDNA obtained during experiments on mammalian tissue; thus the later stages of the protocol are not included here, and readers should follow the accompanying protocol for those. We have previously used our protocol to generate high-quality sequencing libraries for Arabidopsis thaliana inflorescence, Populus tremula developing and dormant leaf buds, and Picea abies female cones. However, we anticipate that the protocol can be adapted to other tissue types and species. The entire protocol for preparing samples and processing libraries can be completed in 3-4 d.

  • 19.
    Hard, Joanna
    et al.
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Al Hakim, Ezeddin
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Kindblom, Marie
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Bjorklund, Asa K.
    Uppsala Univ, Dept Cell & Mol Biol, Natl Bioinformat Infrastruct Sweden, Scilifelab, Uppsala, Sweden..
    Sennblad, Bengt
    Uppsala Univ, Dept Cell & Mol Biol, Natl Bioinformat Infrastruct Sweden, Scilifelab, Uppsala, Sweden..
    Demirci, Ilke
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Paterlini, Marta
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Reu, Pedro
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Borgström, Erik
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Stahl, Patrik L.
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Michaelsson, Jakob
    Karolinska Inst, Dept Med, Ctr Infect Med, Huddinge, Sweden..
    Mold, Jeff E.
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Frisen, Jonas
    Karolinska Inst, Dept Cell & Mol Biol, Solna, Sweden..
    Conbase: a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing2019Inngår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 20, artikkel-id 68Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Accurate variant calling and genotyping represent major limiting factors for downstream applications of single-cell genomics. Here, we report Conbase for the identification of somatic mutations in single-cell DNA sequencing data. Conbase leverages phased read data from multiple samples in a dataset to achieve increased confidence in somatic variant calls and genotype predictions. Comparing the performance of Conbase to three other methods, we find that Conbase performs best in terms of false discovery rate and specificity and provides superior robustness on simulated data, in vitro expanded fibroblasts and clonal lymphocyte populations isolated directly from a healthy human donor.

  • 20.
    Jahn, Michael
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. K.
    Vialas, Vital
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Karlsen, Jan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Maddalo, Gianluca
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Edfors, Fredrik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Käll, Lukas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hudson, Elton P.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Growth of Cyanobacteria Is Constrained by the Abundance of Light and Carbon Assimilation Proteins2018Inngår i: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 25, nr 2, s. 478-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cyanobacteria must balance separate demands for energy generation, carbon assimilation, and biomass synthesis. We used shotgun proteomics to investigate proteome allocation strategies in the model cyanobacterium Synechocystis sp. PCC 6803 as it adapted to light and inorganic carbon (C-i) limitation. When partitioning the proteome into seven functional sectors, we find that sector sizes change linearly with growth rate. The sector encompassing ribosomes is significantly smaller than in E. coli, which may explain the lower maximum growth rate in Synechocystis. Limitation of light dramatically affects multiple proteome sectors, whereas the effect of C-i limitation is weak. Carbon assimilation proteins respond more strongly to changes in light intensity than to C-i. A coarse-grained cell economy model generally explains proteome trends. However, deviations from model predictions suggest that the large proteome sectors for carbon and light assimilation are not optimally utilized under some growth conditions and may constrain the proteome space available to ribosomes.

  • 21.
    Jeuken, Gustavo S.
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Käll, Lukas
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    A simple null model for inferences from network enrichment analysis2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 11, artikkel-id e0206864Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A prevailing technique to infer function from lists of identifications, from molecular biological high-throughput experiments, is over-representation analysis, where the identifications are compared to predefined sets of related genes often referred to as pathways. As at least some pathways are known to be incomplete in their annotation, algorithmic efforts have been made to complement them with information from functional association networks. While the terminology varies in the literature, we will here refer to such methods as Network Enrichment Analysis (NEA). Traditionally, the significance of inferences from NEA has been assigned using a null model constructed from randomizations of the network. Here we instead argue for a null model that more directly relates to the set of genes being studied, and have designed one dynamic programming algorithm that calculates the score distribution of NEA scores that makes it possible to assign unbiased mid p values to inferences. We also implemented a random sampling method, carrying out the same task. We demonstrate that our method obtains a superior statistical calibration as compared to the popular NEA inference engine, BinoX, while also providing statistics that are easier to interpret.

  • 22.
    Johansson, Sebastian
    et al.
    Stockholms Universitet.
    Juhos, Szilveszter
    Stockholms Universitet.
    Redin, David
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Ahmadian, Afshin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Käller, Max
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Comprehensive haplotyping of the HLA gene family using nanopore sequencingManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The HLA gene family is the most polymorphic loci in the human genome; it encodes for the major histocompatibility complexes (MHC) which mediates the immune response in terms of cellular interactions with antigens. Compatibility between HLA alleles is thus of great medical interest for recipients of allogeneic transplantations. Traditional serological techniques to evaluate compatibility are now being replaced by more accurate DNA sequencing-based methods. However, short read sequencing data typically result in collapsed sequences representing a mixture of variants from native haplotypes. In addition, most previous studies have been limited to a few highly polymorphic exons of various HLA genes. Here we present haplotype-resolved full-length sequencing of the six most clinically relevant MHC Class I and Class II genes, to characterize the haplotypes of eight reference individuals, using a single MinION flow cell. The results show that full-length sequencing of single molecules enables haplotypes to be resolved to the highest degree of accuracy (four-field resolution). In this study, a majority of the alleles were classified with four-field resolution and could be verified through previously published genotyping studies. These results support the notion that nanopore sequencing could be a viable solution for highly accurate clinical evaluation of histocompatibility.

  • 23. Järver, P.
    et al.
    Dondalska, A.
    Poux, C.
    Sandberg, A. S.
    Bergenstråhle, Joseph
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Sköld, A. E.
    Dereuddre-Bosquet, N.
    Martinon, F.
    Pålsson, S.
    Zaghloul, E.
    Brodin, D.
    Sander, B.
    Lennox, K. A.
    Behlke, M. A.
    EL-Andaloussi, S.
    Lehtiö, J.
    Lundeberg, Joakim
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    LeGrand, R.
    Spetz, A. -L
    Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, nr 1, artikkel-id 15841Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.

  • 24. Kannan, P.
    et al.
    Kretzschmar, Warren W.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Winter, H.
    Warren, D.
    Bates, R.
    Allen, P. D.
    Syed, N.
    Irving, B.
    Papiez, B. W.
    Kaeppler, J.
    Markelc, B.
    Kinchesh, P.
    Gilchrist, S.
    Smart, S.
    Schnabel, J. A.
    Maughan, T.
    Harris, A. L.
    Muschel, R. J.
    Partridge, M.
    Sharma, R. A.
    Kersemans, V.
    Functional parameters derived from magnetic resonance imaging reflect vascular morphology in preclinical tumors and in human liver metastases2018Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, nr 19, s. 4694-4704Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Tumor vessels influence the growth and response of tumors to therapy. Imaging vascular changes in vivo using dynamic contrast-enhanced MRI (DCE-MRI) has shown potential to guide clinical decision making for treatment. However, quantitative MR imaging biomarkers of vascular function have not been widely adopted, partly because their relationship to structural changes in vessels remains unclear. We aimed to elucidate the relationships between vessel function and morphology in vivo. Experimental Design: Untreated preclinical tumors with different levels of vascularization were imaged sequentially using DCE-MRI and CT. Relationships between functional parameters from MR (iAUC, Ktrans, and BATfrac) and structural parameters from CT (vessel volume, radius, and tortuosity) were assessed using linear models. Tumors treated with anti-VEGFR2 antibody were then imaged to determine whether antiangiogenic therapy altered these relationships. Finally, functional-structural relationships were measured in 10 patients with liver metastases from colorectal cancer. Results: Functional parameters iAUC and Ktrans primarily reflected vessel volume in untreated preclinical tumors. The relationships varied spatially and with tumor vascularity, and were altered by antiangiogenic treatment. In human liver metastases, all three structural parameters were linearly correlated with iAUC and Ktrans. For iAUC, structural parameters also modified each other's effect. Conclusions: Our findings suggest that MR imaging biomarkers of vascular function are linked to structural changes in tumor vessels and that antiangiogenic therapy can affect this link. Our work also demonstrates the feasibility of three-dimensional functional-structural validation of MR biomarkers in vivo to improve their biological interpretation and clinical utility. 

  • 25.
    Lundeberg, Joakim
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Large scale proteomics and proteome mapping in the clinical context2007Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 66, s. 27-27Artikkel i tidsskrift (Annet vitenskapelig)
  • 26. Lundmark, A.
    et al.
    Gerasimcik, N.
    Båge, T.
    Jemt, A.
    Mollbrink, Annelie
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden.
    Salmén, F.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Centre Utrecht, Cancer Genomics Netherlands, Utrecht, The Netherlands.
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Yucel-Lindberg, T.
    Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, nr 1, artikkel-id 9370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Periodontitis is a highly prevalent chronic inflammatory disease of the periodontium, leading ultimately to tooth loss. In order to characterize the gene expression of periodontitis-affected gingival tissue, we have here simultaneously quantified and localized gene expression in periodontal tissue using spatial transcriptomics, combining RNA sequencing with histological analysis. Our analyses revealed distinct clusters of gene expression, which were identified to correspond to epithelium, inflamed areas of connective tissue, and non-inflamed areas of connective tissue. Moreover, 92 genes were identified as significantly up-regulated in inflamed areas of the gingival connective tissue compared to non-inflamed tissue. Among these, immunoglobulin lambda-like polypeptide 5 (IGLL5), signal sequence receptor subunit 4 (SSR4), marginal zone B and B1 cell specific protein (MZB1), and X-box binding protein 1 (XBP1) were the four most highly up-regulated genes. These genes were also verified as significantly higher expressed in gingival tissue of patients with periodontitis compared to healthy controls, using reverse transcription quantitative polymerase chain reaction. Moreover, the protein expressions of up-regulated genes were verified in gingival biopsies by immunohistochemistry. In summary, in this study, we report distinct gene expression signatures within periodontitis-affected gingival tissue, as well as specific genes that are up-regulated in inflamed areas compared to non-inflamed areas of gingival tissue. The results obtained from this study may add novel information on the genes and cell types contributing to pathogenesis of the chronic inflammatory disease periodontitis. 

  • 27.
    Lundmark, Anna
    et al.
    Karolinska Inst, Dept Dent Med, Div Periodontol, Huddinge, Sweden..
    Hu, Yue O. O.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska Inst, CTMR, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Huss, Mikael
    Stockholm Univ, Natl Bioinformat Infrastruct Sweden, Dept Biochem & Biophys, Sci Life Lab, Solna, Sweden..
    Johannsen, Gunnar
    Karolinska Inst, Dept Dent Med, Div Periodontol, Huddinge, Sweden..
    Andersson, Anders F.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Yucel-Lindberg, Tulay
    Karolinska Inst, Dept Dent Med, Div Periodontol, Huddinge, Sweden..
    Identification of Salivary Microbiota and Its Association With Host Inflammatory Mediators in Periodontitis2019Inngår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 9, artikkel-id 216Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Periodontitis is a microbial-induced chronic inflammatory disease, which may not only result in tooth loss, but can also contribute to the development of various systemic diseases. The transition from healthy to diseased periodontium depends on microbial dysbiosis and impaired host immune response. Although periodontitis is a common disease as well as associated with various systemic inflammatory conditions, the taxonomic profiling of the salivary microbiota in periodontitis and its association with host immune and inflammatory mediators has not been reported. Therefore, the aim of this study was to identify key pathogens and their potential interaction with the host's inflammatory mediators in saliva samples for periodontitis risk assessment. The microbial 16S rRNA gene sequencing and the levels of inflammatory mediators were performed in saliva samples from patients with chronic periodontitis and periodontally healthy control subjects. The salivary microbial community composition differed significantly between patients with chronic periodontitis and healthy controls. Our analyses identified a number of microbes, including bacteria assigned to Eubacterium saphenum, Tannerella forsythia, Filifactor alocis, Streptococcus mitis/parasanguinis, Parvimonas micra, Prevotella sp., Phocaeicola sp., and Fretibacterium sp. as more abundant in periodontitis, compared to healthy controls. In samples from healthy individuals, we identified Campylobacter concisus, and Veillonella sp. as more abundant. Integrative analysis of the microbiota and inflammatory mediators/cytokines revealed associations that included positive correlations between the pathogens Treponema sp. and Selenomas sp. and the cytokines chitinase 3-like 1, sIL-6R alpha, sTNF-R1, and gp 130/sIL-6R beta. In addition, a negative correlation was identified between IL-10 and Filifactor alocis. Our results reveal distinct and disease-specific patterns of salivary microbial composition between patients with periodontitis and healthy controls, as well as significant correlations between microbiota and host-mediated inflammatory cytokines. The positive correlations between the pathogens Treponema sp. and Selenomas sp. and the cytokines chitinase 3-like 1, sIL-6R alpha, sTNF-R1, and gp 130/sIL-6R beta might have the future potential to serve as a combined bacteria-host salivary biomarker panel for diagnosis of the chronic infectious disease periodontitis. However, further studies are required to determine the capacity of these microbes and inflammatory mediators as a salivary biomarker panel for periodontitis.

  • 28.
    Maniatis, Silas
    et al.
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA..
    Aijo, Tarmo
    Flatiron Inst, Ctr Computat Biol, New York, NY 10010 USA..
    Vickovic, Sanja
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Braine, Catherine
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA.;Columbia Univ, Mortimer B Zuckerman Mind Brain Behav Inst, New York, NY 10032 USA..
    Kang, Kristy
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA..
    Mollbrink, Annelie
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fagegaltier, Delphine
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA..
    Andrusivova, Zaneta
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Saarenpaa, Sami
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Saiz-Castro, Gonzalo
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Cuevas, Miguel
    Columbia Univ, Mortimer B Zuckerman Mind Brain Behav Inst, New York, NY 10032 USA..
    Watters, Aaron
    Flatiron Inst, Ctr Computat Biol, New York, NY 10010 USA..
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Bonneau, Richard
    Flatiron Inst, Ctr Computat Biol, New York, NY 10010 USA.;NYU, Ctr Data Sci, New York, NY 10011 USA..
    Phatnani, Hemali
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA.;Columbia Univ, Mortimer B Zuckerman Mind Brain Behav Inst, New York, NY 10032 USA..
    Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis2019Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 364, nr 6435, s. 89-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Paralysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spinal tissue remains poorly understood. Here, we use spatial transcriptomics to obtain gene expression measurements of mouse spinal cords over the course of disease, as well as of postmortem tissue from ALS patients, to characterize the underlying molecular mechanisms in ALS. We identify pathway dynamics, distinguish regional differences between microglia and astrocyte populations at early time points, and discern perturbations in several transcriptional pathways shared between murine models of ALS and human postmortem spinal cords.

  • 29.
    Marin-Beltran, Isabel
    et al.
    CSIC, Inst Ciencies Mar, Barcelona, Spain.;Univ Algarve, Ctr Ciencias Mar Algarve CCMAR, Faro, Portugal..
    Logue, Jurg B.
    Lund Univ, Dept Biol Aquat Ecol, Lund, Sweden.;Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst EEMiS, Kalmar, Sweden..
    Andersson, Anders F.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Peters, Francesc
    CSIC, Inst Ciencies Mar, Barcelona, Spain..
    Atmospheric Deposition Impact on Bacterial Community Composition in the NW Mediterranean2019Inngår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, artikkel-id 858Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Atmospheric deposition is a source of inorganic nutrients and organic matter to the ocean, and can favor the growth of some planktonic species over others according to their nutrient requirements. Atmospheric inputs from natural and anthropogenic sources are nowadays increasing due to desertification and industrialization, respectively. While the impact of mineral dust (mainly from the Saharan desert) on phytoplankton and bacterial community composition has been previously assessed, the effect of anthropogenic aerosols on marine bacterial assemblages remains poorly studied. Since marine bacteria play a range of roles in the biogeochemical cycles of inorganic nutrients and organic carbon, it is important to determine which taxa of marine bacteria may benefit from aerosol fertilization and which not. Here, we experimentally assessed the effect of Saharan dust and anthropogenic aerosols on marine bacterioplankton community composition across a spatial and temporal range of trophic conditions in the northwestern Mediterranean Sea. Results from 16S rDNA sequencing showed that bacterial diversity varied significantly with seasonality and geographical location. While atmospheric deposition did not yield significant changes in community composition when all the experiments where considered together, it did produce changes at certain places and during certain times of the year. These effects accounted for shifts in the bacterial community's relative abundance of up to 28%. The effect of aerosols was overall greatest in summer, both types of atmospheric particles stimulating the groups Alphaproteobacteria, Betaproteobacteria, and Cyanobacteria in the location with the highest anthropogenic footprint. Other bacterial groups benefited from one or the other aerosol depending on the season and location. Anthropogenic aerosols increased the relative abundance of groups belonging to the phylum Bacteriodetes (Cytophagia, Flavobacteriia, and Sphingobacteriia), while Saharan dust stimulated most the phytoplanktonic group of Cyanobacteria and, more specifically, Synechococcus.

  • 30.
    Newton, Phillip T.
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, Stockholm, Sweden..
    Li, Lei
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Zhou, Baoyi
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Schweingruber, Christoph
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Hovorakova, Maria
    Czech Acad Sci, Inst Expt Med, Dept Dev Biol, Prague, Czech Republic..
    Xie, Meng
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Sun, Xiaoyan
    Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.;Karolinska Inst, Ctr Innovat Med, Huddinge, Sweden..
    Sandhow, Lakshmi
    Karolinska Inst, Ctr Hematol & Regenerat Med, Huddinge, Sweden..
    Artemov, Artem V.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Sechenov First Moscow State Med Univ, Inst Regenerat Med, Moscow, Russia..
    Ivashkin, Evgeny
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Suter, Simon
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Dyachuk, Vyacheslav
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Russian Acad Sci, Far Eastern Branch, Natl Sci Ctr Marine Biol, Vladivostok, Russia..
    El Shahawy, Maha
    Univ Gothenburg, Sahlgrenska Acad, Dept Oral Biochem, Gothenburg, Sweden..
    Gritli-Linde, Amel
    Univ Gothenburg, Sahlgrenska Acad, Dept Oral Biochem, Gothenburg, Sweden..
    Bouderlique, Thibault
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Petersen, Julian
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Med Univ Vienna, Ctr Brain Res, Dept Mol Neurosci, Vienna, Austria..
    Mollbrink, Annelie
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Enikolopov, Grigori
    SUNY Stony Brook, Ctr Dev Genet, Stony Brook, NY 11794 USA.;SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA..
    Qian, Hong
    Karolinska Inst, Ctr Hematol & Regenerat Med, Huddinge, Sweden..
    Fried, Kaj
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Kasper, Maria
    Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.;Karolinska Inst, Ctr Innovat Med, Huddinge, Sweden..
    Hedlund, Eva
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Adameyko, Igor
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Med Univ Vienna, Ctr Brain Res, Dept Mol Neurosci, Vienna, Austria..
    Savendahl, Lars
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, Stockholm, Sweden..
    Chagin, Andrei S.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Sechenov First Moscow State Med Univ, Inst Regenerat Med, Moscow, Russia..
    A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate2019Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 567, nr 7747, s. 234-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification 1 . However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth 1,2 , but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric celldivision. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.

  • 31.
    Paerl, Ryan W.
    et al.
    Univ Copenhagen, Dept Biol, Marine Biol Sect, DK-3000 Helsingor, Denmark.;North Carolina State Univ, Dept Marine Earth & Atmospher Sci, Raleigh, NC 27695 USA..
    Sundh, John
    Stockholm Univ, Natl Bioinformat Infrastruct Sweden, Sci Life Lab, Dept Biochem & Biophys, S-17121 Solna, Sweden.;KTH Royal Inst Technol, Sci Life Lab, Dept Gene Technol, S-17121 Solna, Sweden..
    Tan, Demeng
    Univ Copenhagen, Dept Biol, Marine Biol Sect, DK-3000 Helsingor, Denmark..
    Svenningsen, Sine L.
    Univ Copenhagen, Dept Biol, Biomol Sci Sect, DK-2200 Copenhagen, Denmark..
    Hylander, Samuel
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, SE-39182 Kalmar, Sweden..
    Pinhassi, Jarone
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, SE-39182 Kalmar, Sweden..
    Andersson, Anders F.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Riemann, Lasse
    Univ Copenhagen, Dept Biol, Marine Biol Sect, DK-3000 Helsingor, Denmark..
    Prevalent reliance of bacterioplankton on exogenous vitamin B1 and precursor availability2018Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, nr 44, s. E10447-E10456Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Vitamin B1 (B1 herein) is a vital enzyme cofactor required by virtually all cells, including bacterioplankton, which strongly influence aquatic biogeochemistry and productivity and modulate climate on Earth. Intriguingly, bacterioplankton can be de novo B1 synthesizers or B1 auxotrophs, which cannot synthesize B1 de novo and require exogenous B1 or B1 precursors to survive. Recent isolate-based work suggests select abundant bacterioplankton are B1 auxotrophs, but direct evidence of B1 auxotrophy among natural communities is scant. In addition, it is entirely unknown if bulk bacterioplankton growth is ever B1-limited. We show by surveying for B1-related genes in estuarine, marine, and freshwater metagenomes and metagenome-assembled genomes (MAGs) that most naturally occurring bacterioplankton are B1 auxotrophs. Pyrimidine B1-auxotrophic bacterioplankton numerically dominated metagenomes, but multiple other B1-auxotrophic types and distinct uptake and B1-salvaging strategies were also identified, including dual (pyrimidine and thiazole) and intact B1 auxotrophs that have received little prior consideration. Time-series metagenomes from the Baltic Sea revealed pronounced shifts in the prevalence of multiple B1-auxotrophic types and in the B1-uptake and B1salvaging strategies over time. Complementarily, we documented B1/precursor limitation of bacterioplankton production in three of five nutrient-amendment experiments at the same time-series station, specifically when intact B1 concentrations were <= 3.7 pM, based on bioassays with a genetically engineered Vibrio anguillarum B1-auxotrophic strain. Collectively, the data presented highlight the prevalent reliance of bacterioplankton on exogenous B1/precursors and on the bioavailability of the micronutrients as an overlooked factor that could influence bacterioplankton growth and succession and thereby the cycling of nutrients and energy in aquatic systems.

  • 32.
    Redin, David
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Phasing single DNA molecules with barcode linked sequencing2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Elucidation of our genetic constituents has in the past decade predominately taken the form of short-read DNA sequencing. Revolutionary technology developments have enabled vast amounts of biological information to be obtained, but from a medical standpoint it has yet to live up to the promise of associating individual genotypes to phenotypic states of wide-spread clinical relevance. The mechanisms by which complex phenotypes arise have been difficult to ascertain and the value of short-read sequencing platforms have been limited in this regard. It has become evident that resolving the full spectrum of genetic heterogeneity requires accurate long range information of individual haplotypes to be distinguished. Long-range haplotyping information can be obtained experimentally by long-read sequencing platforms or through linkage of short sequencing reads by means of a common barcode. This thesis explores these solutions, primarily through the development of novel technologies to phase short sequences of single molecules using DNA barcoding. A new method for high-throughput phasing of single DNA molecules, achieved by the production and utilization of uniquely barcoded beads in emulsion droplets, is described in Paper I. The results confirm that complex libraries of beads featuring mutually exclusive barcodes can be generated through clonal PCR amplification, and that these beads can be used to phase variations of the 16s rRNA gene which reduces the ambiguity of classifying bacterial species for metagenomics. Paper II describes a second methodology (‘Droplet Barcode Sequencing’) which simplifies the concept of barcoding DNA fragments by omitting the need for beads and instead relying on clonal amplification of single barcoding oligonucleotides. This study also increases the amount of information that can be linked, which is showcased by phasing all exons of the HLA-A gene and successfully resolving all the alleles present in a sample pool of eight individuals. Paper III expands on this work and explores the use of a single molecule sequencing platform to provide full-length sequencing coverage of six genes of the HLA family. The results show that while genes shorter than 10 kb can be resolved with a high degree of accuracy, compensating for a relatively high error rate by means of increased coverage can be challenging for larger genomic loci. Finally, Paper IV introduces the use of barcode-linked reads on an unprecedented scale, with a new assay that enables low-cost haplotyping of whole genomes without the need for predetermined capture sequences. This technology is utilized to generate a haplotype-resolved human genome, call large-scale structural variants and perform reference-free assembly of bacterial and human genomes. At a cost of only $19 USD per sample, this technology makes the benefits of long-range haplotyping available to the vast majority of laboratories which currently rely solely on short-read sequencing platforms.

  • 33.
    Redin, David
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Frick, Tobias
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Aghelpasand, Hooman
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Theland, Jennifer
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Käller, Max
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Borgström, Erik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Olsen, Remi-Andre
    Stockholms Universitet.
    Ahmadian, Afshin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Efficient whole genome haplotyping and single molecule phasing with barcode-linked readsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The future of human genomics is one that seeks to resolve the entirety of genetic variation through sequencing. The prospect of utilizing genomics for medical purposes require cost-efficient and accurate base calling, long-range haplotyping capability, and reliable calling of structural variants. Short-read sequencing has lead the development towards such a future but has struggled to meet the latter two of these needs. To address this limitation, we developed a technology that preserves the molecular origin of short sequencing reads, with an insignificant increase to sequencing costs. We demonstrate a library preparation method which enables whole genome haplotyping, long-range phasing of single DNA molecules, and de novo genome assembly through barcode-linked reads (BLR). Millions of random barcodes are used to reconstruct megabase-scale phase blocks and call structural variants. We also highlight the versatility of our technology by generating libraries from different organisms using picograms to nanograms of input material.

  • 34. Rubin, C.
    et al.
    Nathanaelsson, C.
    KTH.
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Nilsson, O.
    Ljunggren, O.
    Kindmark, A.
    MicroRNA repertoire of primary human bone derived cells and MG63-cells - Polymorphic binding sites in putative target genes2007Inngår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 80, s. S34-S35Artikkel i tidsskrift (Annet vitenskapelig)
  • 35.
    Salmén, Fredrik
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Ståhl, Patrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mollbrink, Annelie
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Navarro Fernandez, José Carlos
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Vickovic, Sanja
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Frisen, Jonas
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden..
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Barcoded solid-phase RNA capture for Spatial Transcriptomics profiling in mammalian tissue sections2018Inngår i: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 13, nr 11, s. 2501-2534Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Spatial resolution of gene expression enables gene expression events to be pinpointed to a specific location in biological tissue. Spatially resolved gene expression in tissue sections is traditionally analyzed using immunohistochemistry (IHC) or in situ hybridization (ISH). These technologies are invaluable tools for pathologists and molecular biologists; however, their throughput is limited to the analysis of only a few genes at a time. Recent advances in RNA sequencing (RNA-seq) have made it possible to obtain unbiased high-throughput gene expression data in bulk. Spatial Transcriptomics combines the benefits of traditional spatially resolved technologies with the massive throughput of RNA-seq. Here, we present a protocol describing how to apply the Spatial Transcriptomics technology to mammalian tissue. This protocol combines histological staining and spatially resolved RNA-seq data from intact tissue sections. Once suitable tissue-specific conditions have been established, library construction and sequencing can be completed in similar to 5-6 d. Data processing takes a few hours, with the exact timing dependent on the sequencing depth. Our method requires no special instruments and can be performed in any laboratory with access to a cryostat, microscope and next-generation sequencing.

  • 36.
    Smith, Bradley P.
    et al.
    Cent Queensland Univ, Sch Hlth Med & Appl Sci, Adelaide, SA 5034, Australia..
    Cairns, Kylie M.
    Univ New South Wales, Sch Biol Earth & Environm Sci, Ctr Ecosyst Sci, Sydney, NSW 2052, Australia..
    Adams, Justin W.
    Monash Univ, Dept Anat & Dev Biol, Melbourne, Vic 3800, Australia..
    Newsome, Thomas M.
    Univ Sydney, Sch Life & Environm Sci, Sydney, NSW 2006, Australia..
    Fillios, Melanie
    Univ New England, Humanities Arts & Social Sci, Armidale, NSW 2351, Australia..
    Deaux, Eloise C.
    Univ Neuchatel, Dept Comparat Cognit, CH-2000 Neuchatel, Switzerland..
    Parr, William C. H.
    Univ New South Wales, Surg & Orthopaed Res Lab, Sydney, NSW 2052, Australia..
    Letnic, Mike
    Univ New South Wales, Sch Biol Earth & Environm Sci, Ctr Ecosyst Sci, Sydney, NSW 2052, Australia..
    Van Eeden, Lily M.
    Univ Sydney, Sch Life & Environm Sci, Desert Ecol Res Grp, Sydney, NSW 2006, Australia..
    Appleby, Robert G.
    Griffith Univ, Environm Futures Res Inst, Nathan, Qld 4111, Australia..
    Bradshaw, Corey J. A.
    Flinders Univ S Australia, Coll Sci & Engn, Global Ecol, Adelaide, SA 5001, Australia..
    Savolainen, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Ritchie, Euan G.
    Deakin Univ, Sch Life & Environm Sci, Ctr Integrat Ecol, Burwood Campus, Geelong, Vic 3125, Australia..
    Nimmo, Dale G.
    Charles Sturt Univ, Sch Environm Sci, Albury, NSW 2650, Australia..
    Archer-Lean, Clare
    Univ Sunshine Coast, Sch Commun & Creat Ind, Maroochydore, Qld 4558, Australia..
    Greenville, Aaron C.
    Univ Sydney, Sch Life & Environm Sci, Desert Ecol Res Grp, Sydney, NSW 2006, Australia.;Univ Technol Sydney, Sch Life Sci, Ultimo, NSW 2007, Australia..
    Dickman, Christopher R.
    Univ Sydney, Sch Life & Environm Sci, Desert Ecol Res Grp, Sydney, NSW 2006, Australia..
    Watson, Lyn
    Australian Dingo Fdn, Gisborne, Vic 3437, Australia..
    Moseby, Katherine E.
    Univ New South Wales, Sch Biol Earth & Environm Sci, Ctr Ecosyst Sci, Sydney, NSW 2052, Australia..
    Doherty, Tim S.
    Deakin Univ, Sch Life & Environm Sci, Ctr Integrat Ecol, Burwood Campus, Geelong, Vic 3125, Australia..
    Wallach, Arian D.
    Univ Technol Sydney, Fac Sci, Ctr Compassionate Conservat, Ultimo, NSW 2007, Australia..
    Morrant, Damian S.
    Biosphere Environm Consultants, Cairns, Qld 4870, Australia..
    Crowther, Mathew S.
    Univ Sydney, Sch Life & Environm Sci, Sydney, NSW 2006, Australia..
    Taxonomic status of the Australian dingo: the case for Canis dingo Meyer, 17932019Inngår i: Zootaxa, ISSN 1175-5326, E-ISSN 1175-5334, Vol. 4564, nr 1, s. 173-197Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The taxonomic status and systematic nomenclature of the Australian dingo remain contentious, resulting in decades of inconsistent applications in the scientific literature and in policy. Prompted by a recent publication calling for dingoes to be considered taxonomically as domestic dogs (Jackson et al. 2017, Zootaxa 4317, 201-224), we review the issues of the taxonomy applied to canids, and summarise the main differences between dingoes and other canids. We conclude that (1) the Australian dingo is a geographically isolated (allopatric) species from all other Canis, and is genetically, phenotypically, ecologically, and behaviourally distinct; and (2) the dingo appears largely devoid of many of the signs of domestication, including surviving largely as a wild animal in Australia for millennia. The case of defining dingo taxonomy provides a quintessential example of the disagreements between species concepts (e.g., biological, phylogenetic, ecological, morphological). Applying the biological species concept sensu stricto to the dingo as suggested by Jackson et al. (2017) and consistently across the Canidae would lead to an aggregation of all Canis populations, implying for example that dogs and wolves are the same species. Such an aggregation would have substantial implications for taxonomic clarity, biological research, and wildlife conservation. Any changes to the current nomen of the dingo (currently Canis dingo Meyer, 1793), must therefore offer a strong, evidence-based argument in favour of it being recognised as a subspecies of Canis lupus Linnaeus, 1758, or as Canis familiaris Linnaeus, 1758, and a successful application to the International Commission for Zoological Nomenclature - neither of which can be adequately supported. Although there are many species concepts, the sum of the evidence presented in this paper affirms the classification of the dingo as a distinct taxon, namely Canis dingo.

  • 37.
    The, Matthew
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Statistical and machine learning methods to analyze large-scale mass spectrometry data2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Modern biology is faced with vast amounts of data that contain valuable information yet to be extracted. Proteomics, the study of proteins, has repositories with thousands of mass spectrometry experiments. These data gold mines could further our knowledge of proteins as the main actors in cell processes and signaling. Here, we explore methods to extract more information from this data using statistical and machine learning methods.

    First, we present advances for studies that aggregate hundreds of runs. We introduce MaRaCluster, which clusters mass spectra for large-scale datasets using statistical methods to assess similarity of spectra. It identified up to 40% more peptides than the state-of-the-art method, MS-Cluster. Further, we accommodated large-scale data analysis in Percolator, a popular post-processing tool for mass spectrometry data. This reduced the runtime for a draft human proteome study from a full day to 10 minutes.

    Second, we clarify and promote the contentious topic of protein false discovery rates (FDRs). Often, studies report lists of proteins but fail to report protein FDRs. We provide a framework to systematically discuss protein FDRs and take away hesitance. We also added protein FDRs to Percolator, opting for the best-peptide approach which proved superior in a benchmark of scalable protein inference methods.

    Third, we tackle the low sensitivity of protein quantification methods. Current methods lack proper control of error sources and propagation. To remedy this, we developed Triqler, which controls the protein quantification FDR through a Bayesian framework. We also introduce MaRaQuant, which proposes a quantification-first approach that applies clustering prior to identification. This reduced the number of spectra to be searched and allowed us to spot unidentified analytes of interest. Combining these tools outperformed the state-of-the-art method, MaxQuant/Perseus, and found enriched functional terms for datasets that had none before.

  • 38.
    The, Matthew
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Käll, Lukas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Distillation of label-free quantification data by clustering and Bayesian modelingManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    In shotgun proteomics, the amount of information that can be extracted from label-free quantification experiments is typically limited by the identification rate as well as the noise level of the quantitative signals. This generally causes a low sensitivity in differential expression analysis on protein level. Here, we present a new method, MaRaQuant, in which we reverse the typical identification-first workflow into a quantification-first approach. Specifically, we apply unsupervised clustering on both MS1 and MS2 level to summarize all analytes of interest without assigning identities. This ensures that no valuable information is discarded due to analytes missing identification thresholds and allows us to spend more effort on the identification process due to the data reduction achieved by clustering. Furthermore, we propagate error probabilities from feature level all the way to protein level and input these to our probabilistic protein quantification method, Triqler. Applying this methodology to an engineered dataset, we managed to identify multiple analytes of interest that would have gone unnoticed in traditional pipelines, specifically, through the use of open modification and de novo searches. MaRaQuant/Triqler obtains significantly more identifications on all levels compared to MaxQuant/Perseus, including differentially expressed proteins. Notably, we managed to identify differentially expressed proteins in a clinical dataset where previously none were discovered. Furthermore, our differentially expressed proteins allowed us to attribute multiple functional annotation terms to both clinical datasets that we investigated.

  • 39.
    The, Matthew
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Käll, Lukas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Integrated identification and quantification error probabilities for shotgun proteomicsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Protein quantification by label-free shotgun proteomics experiments is plagued by a multitude of error sources. Typical pipelines for identifying differentially expressed proteins use intermediate filters in an attempt to control the error rate. However, they often ignore certain error sources and, moreover, regard filtered lists as completely correct in subsequent steps. These two indiscretions can easily lead to a loss of control of the false discovery rate (FDR). We propose a probabilistic graphical model, Triqler, that propagates error information through all steps, employing distributions in favor of point estimates, most notably for missing value imputation. The model outputs posterior probabilities for fold changes between treatment groups, highlighting uncertainty rather than hiding it. We analyzed 3 engineered datasets and achieved FDR control and high sensitivity, even for truly absent proteins. In a bladder cancer clinical dataset we discovered 35 proteins at 5% FDR, with the original study discovering none at this threshold. Compellingly, these proteins showed enrichment for functional annotation terms. The model executes in minutes and is freely available at https://pypi.org/project/triqler/.

  • 40.
    Thrane, Kim
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Eriksson, Hanna
    Karolinska Inst, Dept Oncol Pathol, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Oncol, SE-17176 Stockholm, Sweden..
    Maaskola, Jonas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hansson, Johan
    Karolinska Inst, Dept Oncol Pathol, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Oncol, SE-17176 Stockholm, Sweden..
    Lundeberg, Joakim
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Spatially Resolved Transcriptomics Enables Dissection of Genetic Heterogeneity in Stage III Cutaneous Malignant Melanoma2018Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, nr 20, s. 5970-5979Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cutaneous malignant melanoma (melanoma) is characterized by a high mutational load, extensive intertumoral and intratumoral genetic heterogeneity, and complex tumor microenvironment (TME) interactions. Further insights into the mechanisms underlying melanoma are crucial for understanding tumor progression and responses to treatment. Here we adapted the technology of spatial transcriptomics (ST) to melanoma lymph node biopsies and successfully sequenced the transcriptomes of over 2,200 tissue domains. Deconvolution combined with traditional approaches for dimensional reduction of transcriptome-wide data enabled us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Our unsupervised analysis revealed a complex spatial intratumoral composition of melanoma metastases that was not evident through morphologic annotation. Each biopsy showed distinct gene expression profiles and included examples of the coexistence of multiple melanoma signatures within a single tumor region as well as shared profiles for lymphoid tissue characterized according to their spatial location and gene expression profiles. The lymphoid area in close proximity to the tumor region displayed a specific expression pattern, which may reflect the TME, a key component to fully understanding tumor progression. In conclusion, using the ST technology to generate gene expression profiles reveals a detailed landscape of melanoma metastases. This should inspire researchers to integrate spatial information into analyses aiming to identify the factors underlying tumor progression and therapy outcome. Significance: Applying ST technology to gene expression profiling in melanoma lymph node metastases reveals a complex transcriptional landscape in a spatial context, which is essential for understanding the multiple components of tumor progression and therapy outcome. (C) 2018 AACR.

  • 41.
    Tiukova, Ievgeniia A.
    et al.
    Chalmers Univ Technol, Dept Biol & Biol Engn, Syst & Synthet Biol, Gothenburg, Sweden.;Swedish Univ Agr Sci, Dept Mol Sci, Uppsala, Sweden..
    Pettersson, Mats E.
    Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden..
    Hoeppner, Marc P.
    Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden.;NBIS, Uppsala, Sweden.;Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.;Royal Inst Technol KTH, Sci Life Lab, Div Gene Technol, Sch Biotechnol, Solna, Sweden..
    Olsen, Remi-Andre
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Käller, Max
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. Stockholm Univ, Dept Biochem & Biophys, SciLifeLab, Stockholm, Sweden..
    Nielsen, Jens
    Chalmers Univ Technol, Dept Biol & Biol Engn, Syst & Synthet Biol, Gothenburg, Sweden..
    Dainat, Jacques
    Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden.;NBIS, Uppsala, Sweden..
    Lantz, Henrik
    Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden.;NBIS, Uppsala, Sweden..
    Soderberg, Jonas
    Uppsala Univ, Dept Cell & Mol Biol, Mol Evolut, Uppsala, Sweden..
    Passoth, Volkmar
    Swedish Univ Agr Sci, Dept Mol Sci, Uppsala, Sweden..
    Chromosomal genome assembly of the ethanol production strain CBS 11270 indicates a highly dynamic genome structure in the yeast species Brettanomyces bruxellensis2019Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 5, artikkel-id e0215077Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here, we present the genome of the industrial ethanol production strain Brettanomyces bruxellensis CBS 11270. The nuclear genome was found to be diploid, containing four chromosomes with sizes of ranging from 2.2 to 4.0 Mbp. A 75 Kbp mitochondrial genome was also identified. Comparing the homologous chromosomes, we detected that 0.32% of nucleotides were polymorphic, i.e. formed single nucleotide polymorphisms (SNPs), 40.6% of them were found in coding regions (i.e. 0.13% of all nucleotides formed SNPs and were in coding regions). In addition, 8,538 indels were found. The total number of protein coding genes was 4897, of them, 4,284 were annotated on chromosomes; and the mitochondrial genome contained 18 protein coding genes. Additionally, 595 genes, which were annotated, were on contigs not associated with chromosomes. A number of genes was duplicated, most of them as tandem repeats, including a six-gene cluster located on chromosome 3. There were also examples of interchromosomal gene duplications, including a duplication of a six-gene cluster, which was found on both chromosomes 1 and 4. Gene copy number analysis suggested loss of heterozygosity for 372 genes. This may reflect adaptation to relatively harsh but constant conditions of continuous fermentation. Analysis of gene topology showed that most of these losses occurred in clusters of more than one gene, the largest cluster comprising 33 genes. Comparative analysis against the wine isolate CBS 2499 revealed 88,534 SNPs and 8,133 indels. Moreover, when the scaffolds of the CBS 2499 genome assembly were aligned against the chromosomes of CBS 11270, many of them aligned completely, some have chunks aligned to different chromosomes, and some were in fact rearranged. Our findings indicate a highly dynamic genome within the species B. bruxellensis and a tendency towards reduction of gene number in long-term continuous cultivation.

  • 42.
    Wong, Kim
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Navarro, Jose Fernandez
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Bergenstrahle, Ludvig
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Royal Inst Technol KTH, Sch Biotechnol, Div Gene Technol, Sci Life Lab, SE-10691 Solna, Sweden..
    Stahl, Patrik L.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    ST Spot Detector: a web-based application for automatic spot and tissue detection for spatial Transcriptomics image datasets2018Inngår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 34, nr 11, s. 1966-1968Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Motiviation: Spatial Transcriptomics (ST) is a method which combines high resolution tissue imaging with high troughput transcriptome sequencing data. This data must be aligned with the images for correct visualization, a process that involves several manual steps. Results: Here we present ST Spot Detector, a web tool that automates and facilitates this alignment through a user friendly interface.

  • 43.
    Zhang, Miao
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Material- och nanofysik. KTH.
    Ngampeerapong, Chonmanart
    Redin, David
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ahmadian, Afshin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sychugov, Ilya
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Material- och nanofysik.
    Linnros, Jan
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Material- och nanofysik.
    Thermophoresis-Controlled Size-Dependent DNA Translocation through an Array of Nanopores2018Inngår i: ACS Nano, ISSN 1936-0851, E-ISSN 1936-086X, Vol. 12, nr 5, s. 4574-4582Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Large arrays of nanopores can be used for high-throughput biomolecule translocation with applications toward size discrimination and sorting at the single-molecule level. In this paper, we propose to discriminate DNA length by the capture rate of the molecules to an array of relatively large nanopores (50–130 nm) by introducing a thermal gradient by laser illumination in front of the pores balancing the force from an external electric field. Nanopore arrays defined by photolithography were batch processed using standard silicon technology in combination with electrochemical etching. Parallel translocation of single, fluorophore-labeled dsDNA strands is recorded by imaging the array with a fast CMOS camera. The experimental data show that the capture rates of DNA molecules decrease with increasing DNA length due to the thermophoretic effect of the molecules. It is shown that the translocation can be completely turned off for the longer molecule using an appropriate bias, thus allowing a size discrimination of the DNA translocation through the nanopores. A derived analytical model correctly predicts the observed capture rate. Our results demonstrate that by combining a thermal and a potential gradient at the nanopores, such large nanopore arrays can potentially be used as a low-cost, high-throughput platform for molecule sensing and sorting.

  • 44.
    Åkerborg, Örjan
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Spalinskas, Rapolas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Pradhananga, Sailendra
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Anil, Anandashankar
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Höjer, Pontus
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Poujade, Flore-Anne
    Karolinska Inst, Cardiovasc Med Unit, Dept Med, Ctr Mol Med, Stockholm, Sweden..
    Folkersen, Lasse
    Tech Univ Denmark, Dept Bioinformat, Copenhagen, Denmark..
    Sahlén, Pelin
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Eriksson, Per
    Karolinska Inst, Cardiovasc Med Unit, Dept Med, Ctr Mol Med, Stockholm, Sweden..
    High-Resolution Regulatory Maps Connect Vascular Risk Variants to Disease-Related Pathways2019Inngår i: Circulation. Genomic and precision medicine, ISSN 2574-8300, Vol. 12, nr 3, artikkel-id e002353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Genetic variant landscape of coronary artery disease is dominated by noncoding variants among which many occur within putative enhancers regulating the expression levels of relevant genes. It is crucial to assign the genetic variants to their correct genes both to gain insights into perturbed functions and better assess the risk of disease. METHODS: In this study, we generated high-resolution genomic interaction maps (similar to 750 bases) in aortic endothelial, smooth muscle cells and THP-1 (human leukemia monocytic cell line) macrophages stimulated with lipopolysaccharide using Hi-C coupled with sequence capture targeting 25 429 features, including variants associated with coronary artery disease. We also sequenced their transcriptomes and mapped putative enhancers using chromatin immunoprecipitation with an antibody against H3K27Ac. RESULTS: The regions interacting with promoters showed strong enrichment for enhancer elements and validated several previously known interactions and enhancers. We detected interactions for 727 risk variants obtained by genome-wide association studies and identified novel, as well as established genes and functions associated with cardiovascular diseases. We were able to assign potential target genes for additional 398 genome-wide association studies variants using haplotype information, thereby identifying additional relevant genes and functions. Importantly, we discovered that a subset of risk variants interact with multiple promoters and their expression levels were strongly correlated. CONCLUSIONS: In summary, we present a catalog of candidate genes regulated by coronary artery disease-related variants and think that it will be an invaluable resource to further the investigation of cardiovascular pathologies and disease.

1 - 44 of 44
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf