| 1. |
- Bihary, Dóra, et al.
(author)
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Simulation of communication and cooperation in multispecies bacterial communities with an agent based model
- 2012
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In: Scalable computing. - 1895-1767. ; 13:1, s. 21-28
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Journal article (peer-reviewed)abstract
- Members of bacterial communities communicate and cooperate via diffusible chemical materials they emit into the environment, and at the same time, they also compete for nutrients and space. Agent-based models (ABMs) are useful tools for simulating the growth of communities containing multiple interacting microbial species. In this work we present numerical indices characterizing spatial distribution and the fitness of competing bacterial species in an ABM and we present data on how these indices can be used to visually summarize large scale simulation experiments. Preliminary results show bacterial agents utilizing different nutrients but sharing communication signals and public goods can form stable mixed communities in which the species grow faster than any of the single species alone.
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| 2. |
- Halvorsen, Matthew, et al.
(author)
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Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1, s. 1842-
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Journal article (peer-reviewed)abstract
- Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.
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| 3. |
- Miranda, Helder, et al.
(author)
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Co-expression analysis, proteomic and metabolomic study on the impact of a Deg/HtrA protease triple mutant in Synechocystis sp. PCC 6803 exposed to temperature and high light stress
- 2013
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In: Journal of Proteomics. - : Elsevier. - 1874-3919 .- 1876-7737. ; 78, s. 294-311
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Journal article (peer-reviewed)abstract
- Members of the DegP/HtrA protease family are widespread in nature and play an important role in proteolysis of misfolded and damaged proteins. The cyanobacterium Synechocystis sp. PCC 6803 contains three Deg proteases, HhoA (Sll1679), HhoB (Sll1427) and HtrA (Slr1204). Using the proteomic or metabolomic approach we investigated a triple deletion mutant (Δdeg) exposed to light or temperature stress. To cope with the stress conditions the triple mutant reduces its energy metabolism and stress-related proteins are induced to protect the cells. Additionally the co-expression of the genes encoding the three proteases with other genes in Synechocystis sp. PCC 6803 was analyzed. While HhoA seems to be involved in house-keeping processes related to protein (re)folding, protein clearance and signaling, the hhoB expression cluster is dominated by genes encoding periplasmic proteins linked to metabolism or signal transduction pathways. The htrA expression pattern is similar to that of genes encoding proteins of the electron transport chain, iron- and nitrogen metabolism. Our integrative approach indicates significant rearrangements in cells depleted of the Deg/HtrA proteases when exposed to stress, both, in the cytoplasmic and extracytoplasmic space.
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| 4. |
- Mähler, Niklas, et al.
(author)
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Synergy : a web resource for exploring gene regulation in Synechocystis sp. PCC6803
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Journal article (peer-reviewed)abstract
- Despite being a highly studied model organism, most genes of the cyanobacterium Synechocystis sp. PCC 6803 encode proteins with completely unknown function. To facilitate studies of gene regulation in Synechocystis, we have developed Synergy (http://synergy.plantgenie.org), a web application integrating co-expression networks and regulatory motif analysis. Co-expression networks were inferred from publicly available microarray experiments, while regulatory motifs were identified using a phylogenetic footprinting approach. Automatically discovered motifs were shown to be enriched in the network neighborhoods of regulatory proteins much more often than in the neighborhoods of non-regulatory genes, showing that the data provide a sound starting point for studying gene regulation in Synechocystis. Concordantly, we provide several case studies demonstrating that Synergy can be used to find biologically relevant regulatory mechanisms in Synechocystis. Synergy can be used to interactively perform analyses such as gene/motif search, network visualization and motif/function enrichment. Considering the importance of Synechocystis for photosynthesis and biofuel research, we believe that Synergy will become a valuable resource to the research community.
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| 5. |
- Netotea, Sergiu, et al.
(author)
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ComPlEx : conservation and divergence of co-expression networks in A. thaliana, Populus and O. sativa
- 2014
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15, s. 106-
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Journal article (peer-reviewed)abstract
- Background: Divergence in gene regulation has emerged as a key mechanism underlying species differentiation. Comparative analysis of co-expression networks across species can reveal conservation and divergence in the regulation of genes. Results: We inferred co-expression networks of A. thaliana, Populus spp. and O. sativa using state-of-the-art methods based on mutual information and context likelihood of relatedness, and conducted a comprehensive comparison of these networks across a range of co-expression thresholds. In addition to quantifying gene-gene link and network neighbourhood conservation, we also applied recent advancements in network analysis to do cross-species comparisons of network properties such as scale free characteristics and gene centrality as well as network motifs. We found that in all species the networks emerged as scale free only above a certain co-expression threshold, and that the high-centrality genes upholding this organization tended to be conserved. Network motifs, in particular the feed-forward loop, were found to be significantly enriched in specific functional subnetworks but where much less conserved across species than gene centrality. Although individual gene-gene co-expression had massively diverged, up to similar to 80% of the genes still had a significantly conserved network neighbourhood. For genes with multiple predicted orthologs, about half had one ortholog with conserved regulation and another ortholog with diverged or non-conserved regulation. Furthermore, the most sequence similar ortholog was not the one with the most conserved gene regulation in over half of the cases. Conclusions: We have provided a comprehensive analysis of gene regulation evolution in plants and built a web tool for Comparative analysis of Plant co-Expression networks (ComPlEx, http:// complex. plantgenie. org/). The tool can be particularly useful for identifying the ortholog with the most conserved regulation among several sequence-similar alternatives and can thus be of practical importance in e. g. finding candidate genes for perturbation experiments.
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| 6. |
- Rentoft, Matilda, et al.
(author)
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A geographically matched control population efficiently limits the number of candidate disease-causing variants in an unbiased whole-genome analysis
- 2019
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 14:3
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Journal article (peer-reviewed)abstract
- Whole-genome sequencing is a promising approach for human autosomal dominant disease studies. However, the vast number of genetic variants observed by this method constitutes a challenge when trying to identify the causal variants. This is often handled by restricting disease studies to the most damaging variants, e. g. those found in coding regions, and overlooking the remaining genetic variation. Such a biased approach explains in part why the genetic causes of many families with dominantly inherited diseases, in spite of being included in whole-genome sequencing studies, are left unsolved today. Here we explore the use of a geographically matched control population to minimize the number of candidate disease-causing variants without excluding variants based on assumptions on genomic position or functional predictions. To exemplify the benefit of the geographically matched control population we apply a typical disease variant filtering strategy in a family with an autosomal dominant form of colorectal cancer. With the use of the geographically matched control population we end up with 26 candidate variants genome wide. This is in contrast to the tens of thousands of candidates left when only making use of available public variant datasets. The effect of the local control population is dual, it (1) reduces the total number of candidate variants shared between affected individuals, and more importantly (2) increases the rate by which the number of candidate variants are reduced as additional affected family members are included in the filtering strategy. We demonstrate that the application of a geographically matched control population effectively limits the number of candidate disease-causing variants and may provide the means by which variants suitable for functional studies are identified genome wide.
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| 7. |
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| 8. |
- Sundell, David, et al.
(author)
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The Plant Genome Integrative Explorer Resource : PlantGenIE.org
- 2015
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 208:4, s. 1149-1156
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Journal article (peer-reviewed)abstract
- Accessing and exploring large-scale genomics data sets remains a significant challenge to researchers without specialist bioinformatics training. We present the integrated PlantGenIE.org platform for exploration of Populus, conifer and Arabidopsis genomics data, which includes expression networks and associated visualization tools. Standard features of a model organism database are provided, including genome browsers, gene list annotation, BLAST homology searches and gene information pages. Community annotation updating is supported via integration of WebApollo. We have produced an RNA-sequencing (RNA-Seq) expression atlas for Populus tremula and have integrated these data within the expression tools. An updated version of the COMPLEX resource for performing comparative plant expression analyses of gene coexpression network conservation between species has also been integrated. The PlantGenIE.org platform provides intuitive access to large-scale and genome-wide genomics data from model forest tree species, facilitating both community contributions to annotation improvement and tools supporting use of the included data resources to inform biological insight.
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| 9. |
- Wagner, Raik, et al.
(author)
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Deletion of FtsH11 protease has impact on chloroplast structure and function in Arabidopsis thaliana when grown under continuous light
- 2016
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In: Plant Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 39:11, s. 2530-2544
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Journal article (peer-reviewed)abstract
- The membrane-integrated metalloprotease FtsH11 of Arabidopsis thaliana is proposed to be dual-targeted to mitochondria and chloroplasts. A bleached phenotype was observed in ftsh11 grown at long days or continuous light, pointing to disturbances in the chloroplast. Within the chloroplast, FtsH11 was found to be located exclusively in the envelope. Two chloroplast-located proteins of unknown function (Tic22-like protein and YGGT-A) showed significantly higher abundance in envelope membranes and intact chloroplasts of ftsh11 and therefore qualify as potential substrates for the FtsH11 protease. No proteomic changes were observed in the mitochondria of 6-week-old ftsh11 compared with wild type, and FtsH11 was not immunodetected in these organelles. The abundance of plastidic proteins, especially of photosynthetic proteins, was altered even during standard growth conditions in total leaves of ftsh11. At continuous light, the amount of photosystem I decreased relative to photosystem II, accompanied by a drastic change of the chloroplast morphology and a drop of non-photochemical quenching. FtsH11 is crucial for chloroplast structure and function during growth in prolonged photoperiod. The membrane-integrated metalloprotease FtsH11 of Arabidopsis thaliana was found to be located exclusively in the chloroplast envelope and to be crucial for chloroplast structure and function during growth in prolonged photoperiod. Two chloroplast-located proteins of unknown function (Tic22-like protein and YGGT-A) showed significantly higher abundance in envelope membranes and intact chloroplasts of ftsH11 and therefore qualify as potential substrates for the FtsH11 protease.
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