| 1. |
- Ekdahl, Ylva, et al.
(författare)
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A-to-I editing of microRNAs in the mammalian brain increases during development
- 2012
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 22:8, s. 1477-1487
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Tidskriftsartikel (refereegranskat)abstract
- Adenosine-to-inosine (A-to-I) RNA editing targets double-stranded RNA stem-loop structures in the mammalian brain. It has previously been shown that miRNAs are substrates for A-to-I editing. For the first time, we show that for several definitions of edited miRNA, the level of editing increases with development, thereby indicating a regulatory role for editing during brain maturation. We use high-throughput RNA sequencing to determine editing levels in mature miRNA, from the mouse transcriptome, and compare these with the levels of editing in pri-miRNA. We show that increased editing during development gradually changes the proportions of the two miR-376a isoforms, which previously have been shown to have different targets. Several other miRNAs that also are edited in the seed sequence show an increased level of editing through development. By comparing editing of pri-miRNA with editing and expression of the corresponding mature miRNA, we also show an editing-induced developmental regulation of miRNA expression. Taken together, our results imply that RNA editing influences the miRNA repertoire during brain maturation.
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| 2. |
- Ensterö, Mats, et al.
(författare)
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A computational screen for site selective A-to-I editing detects novel sites in neuron specific Hu proteins
- 2010
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several bioinformatic approaches have previously been used to find novel sites of ADAR mediated A-to-I RNA editing in human. These studies have discovered thousands of genes that are hyper-edited in their non-coding intronic regions, especially in alu retrotransposable elements, but very few substrates that are site-selectively edited in coding regions. Known RNA edited substrates suggest, however, that site selective A-to-I editing is particularly important for normal brain development in mammals. Results: We have compiled a screen that enables the identification of new sites of site-selective editing, primarily in coding sequences. To avoid hyper-edited repeat regions, we applied our screen to the alu-free mouse genome. Focusing on the mouse also facilitated better experimental verification. To identify candidate sites of RNA editing, we first performed an explorative screen based on RNA structure and genomic sequence conservation. We further evaluated the results of the explorative screen by determining which transcripts were enriched for A-G mismatches between the genomic template and the expressed sequence since the editing product, inosine (I), is read as guanosine (G) by the translational machinery. For expressed sequences, we only considered coding regions to focus entirely on re-coding events. Lastly, we refined the results from the explorative screen using a novel scoring scheme based on characteristics for known A-to-I edited sites. The extent of editing in the final candidate genes was verified using total RNA from mouse brain and 454 sequencing. Conclusions: Using this method, we identified and confirmed efficient editing at one site in the Gabra3 gene. Editing was also verified at several other novel sites within candidates predicted to be edited. Five of these sites are situated in genes coding for the neuron-specific RNA binding proteins HuB and HuD.
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| 3. |
- Iglesias, Maria Jesus, et al.
(författare)
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Combined Chromatin and Expression Analysis Reveals Specific Regulatory Mechanisms within Cytokine Genes in the Macrophage Early Immune Response
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2, s. e32306-
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of upregulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response.
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| 4. |
- Khan, Mehmood Alam, et al.
(författare)
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fastphylo : Fast tools for phylogenetics
- 2013
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Ingår i: BMC Bioinformatics. - : BioMed Central. - 1471-2105. ; 14:1, s. 334-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Distance methods are ubiquitous tools in phylogenetics. Their primary purpose may be to reconstruct evolutionary history, but they are also used as components in bioinformatic pipelines. However, poor computational efficiency has been a constraint on the applicability of distance methods on very large problem instances. Results: We present fastphylo, a software package containing implementations of efficient algorithms for two common problems in phylogenetics: estimating DNA/protein sequence distances and reconstructing a phylogeny from a distance matrix. We compare fastphylo with other neighbor joining based methods and report the results in terms of speed and memory efficiency. Conclusions: Fastphylo is a fast, memory efficient, and easy to use software suite. Due to its modular architecture, fastphylo is a flexible tool for many phylogenetic studies.
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| 5. |
- Lagergren, Lars, et al.
(författare)
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Att möta unga på nätet
- 2011
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Ingår i: Adda en vuxen - Om ungdomsarbete på nätet. - : Ungdomsstyrelsen. ; , s. 26-35
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Lagergren, Lars, et al.
(författare)
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Professionella vuxna på nätet
- 2011
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Ingår i: Unga nätmiljöer. - : Studentlitteratur AB. - 9789144071220 ; , s. 211-230
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Mahmudi, Owais, et al.
(författare)
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Genome-wide probabilistic reconciliation analysis across vertebrates
- 2013
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 14:Suppl 15, s. S10-
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Tidskriftsartikel (refereegranskat)abstract
- Gene duplication is considered to be a major driving force in evolution that enables the genome of a species to acquire new functions. A reconciliation - a mapping of gene tree vertices to the edges or vertices of a species tree explains where gene duplications have occurred on the species tree. In this study, we sample reconciliations from a posterior over reconciliations, gene trees, edge lengths and other parameters, given a species tree and gene sequences. We employ a Bayesian analysis tool, based on the probabilistic model DLRS that integrates gene duplication, gene loss and sequence evolution under a relaxed molecular clock for substitution rates, to obtain this posterior. By applying these methods, we perform a genome-wide analysis of a nine species dataset, OPTIC, and conclude that for many gene families, the most parsimonious reconciliation (MPR) - a reconciliation that minimizes the number of duplications - is far from the correct explanation of the evolutionary history. For the given dataset, we observe that approximately 19% of the sampled reconciliations are different from MPR. This is in clear contrast with previous estimates, based on simpler models and less realistic assumptions, according to which 98% of the reconciliations can be expected to be identical to MPR. We also generate heatmaps showing where in the species trees duplications have been most frequent during the evolution of these species.
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| 8. |
- Parviainen, Pekka, et al.
(författare)
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Learning bounded tree-width Bayesian networks using integer linear programming
- 2014
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Ingår i: Journal of machine learning research. - : Microtome Publishing. - 1532-4435 .- 1533-7928. ; 33, s. 751-759
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Tidskriftsartikel (refereegranskat)abstract
- In many applications one wants to compute conditional probabilities given a Bayesian network. This inference problem is NP-hard in general but becomes tractable when the network has low tree-width. Since the inference problem is common in many application areas, we provide a practical algorithm for learning bounded tree-width Bayesian networks. We cast this problem as an integer linear program (ILP). The program can be solved by an anytime algorithm which provides upper bounds to assess the quality of the found solutions. A key component of our program is a novel integer linear formulation for bounding tree-width of a graph. Our tests clearly indicate that our approach works in practice, as our implementation was able to find an optimal or nearly optimal network for most of the data sets.
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| 9. |
- Sehat, Bita, et al.
(författare)
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SUMOylation Mediates the Nuclear Translocation and Signaling of the IGF-1 Receptor
- 2010
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 3:108
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Tidskriftsartikel (refereegranskat)abstract
- The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in developmental and cancer biology. Most of its biological effects have been ascribed to its tyrosine kinase activity, which propagates signaling through the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. Here, we report that IGF-1 promotes the modification of IGF-1R by small ubiquitin-like modifier protein-1 (SUMO-1) and its translocation to the nucleus. Nuclear IGF-1R associated with enhancer-like elements and increased transcription in reporter assays. The SUMOylation sites of IGF-1R were identified as three evolutionarily conserved lysine residues-Lys(1025), Lys(1100), and Lys(1120)-in the beta subunit of the receptor. Mutation of these SUMO-1 sites abolished the ability of IGF-1R to translocate to the nucleus and activate transcription, but did not alter its kinase-dependent signaling. Thus, we demonstrate a SUMOylation-mediated mechanism of IGF-1R signaling that has potential implications for gene regulation.
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| 10. |
- Shahrabi Farahani, Hossein, et al.
(författare)
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A Linear Programming Approach for Learning Bounded Treewidth Bayesian Networks
- 2013
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In many applications, one wants to compute conditional probabilities from a Bayesian network. This inference problem is NP-hard in general but becomes tractable when the network has bounded treewidth. Motivated by the needs of applications, we study learning bounded treewidth Bayesian networks. We formulate this problem as a mixed integer linear program (MILP) which can be solved by an anytime algorithm.
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