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Netotea, Sergiu
Publications (5 of 5) Show all publications
Rentoft, M., Svensson, D., Sjödin, A., Olason, P. I., Sjöström, O., Nylander, C., . . . Johansson, E. (2019). A geographically matched control population efficiently limits the number of candidate disease-causing variants in an unbiased whole-genome analysis. PLoS ONE, 14(3), Article ID e0213350.
Open this publication in new window or tab >>A geographically matched control population efficiently limits the number of candidate disease-causing variants in an unbiased whole-genome analysis
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 3, article id e0213350Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Public Library of Science, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-158021 (URN)10.1371/journal.pone.0213350 (DOI)000462465800028 ()30917156 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2011.0042
Available from: 2019-04-10 Created: 2019-04-10 Last updated: 2019-04-12Bibliographically approved
Wagner, R., Von Sydow, L., Aigner, H., Netotea, S., Brugière, S., Sjögren, L., . . . Funk, C. (2016). Deletion of FtsH11 protease has impact on chloroplast structure and function in Arabidopsis thaliana when grown under continuous light. Plant, Cell and Environment, 39(11), 2530-2544
Open this publication in new window or tab >>Deletion of FtsH11 protease has impact on chloroplast structure and function in Arabidopsis thaliana when grown under continuous light
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2016 (English)In: Plant, Cell and Environment, ISSN 0140-7791, E-ISSN 1365-3040, Vol. 39, no 11, p. 2530-2544Article in journal (Refereed) Published
Abstract [en]

The membrane-integrated metallo-protease 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 weeks old ftsH11 compared to 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 PSI decreased relative to PSII, accompanied by a drastic change of the chloroplast morphology and a drop of NPQ. FtsH11 is crucial for chloroplast structure and function during growth in prolonged photoperiod.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016
Keywords
envelope, light acclimation
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-124441 (URN)10.1111/pce.12808 (DOI)000385842400015 ()27479913 (PubMedID)
Available from: 2016-08-11 Created: 2016-08-11 Last updated: 2018-06-07Bibliographically approved
Sundell, D., Mannapperuma, C., Netotea, S., Delhomme, N., Lin, Y.-C., Sjödin, A., . . . Street, N. R. (2015). The Plant Genome Integrative Explorer Resource: PlantGenIE.org. New Phytologist, 208(4), 1149-1156
Open this publication in new window or tab >>The Plant Genome Integrative Explorer Resource: PlantGenIE.org
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2015 (English)In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 208, no 4, p. 1149-1156Article in journal (Refereed) Published
Abstract [en]

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

Keywords
annotation, coexpression, conifer, database, genome browser, Populus, transcriptomics, web source
National Category
Botany
Identifiers
urn:nbn:se:umu:diva-113426 (URN)10.1111/nph.13557 (DOI)000365393000016 ()26192091 (PubMedID)
Available from: 2015-12-18 Created: 2015-12-18 Last updated: 2018-06-07Bibliographically approved
Netotea, S., Sundell, D., Street, N. R. & Hvidsten, T. R. (2014). ComPlEx: conservation and divergence of co-expression networks in A. thaliana, Populus and O. sativa. BMC Genomics, 15, 106
Open this publication in new window or tab >>ComPlEx: conservation and divergence of co-expression networks in A. thaliana, Populus and O. sativa
2014 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, p. 106-Article in journal (Refereed) Published
Abstract [en]

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

National Category
Genetics
Identifiers
urn:nbn:se:umu:diva-88337 (URN)10.1186/1471-2164-15-106 (DOI)000332597700001 ()
Available from: 2014-06-10 Created: 2014-04-30 Last updated: 2018-06-07Bibliographically approved
Miranda, H., Charegi, O., Netotea, S., Hvidsten, T. R., Moritz, T. & Funk, C. (2013). 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. Journal of Proteomics, 78, 294-311
Open this publication in new window or tab >>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
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2013 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 78, p. 294-311Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Cyanobacteria, Synechocystis sp. PCC 6803, heat shock, high light, Deg/HtrA proteases, proteome, co-expression, metabolites
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-60182 (URN)10.1016/j.jprot.2012.09.036 (DOI)000316706800024 ()
Available from: 2012-10-04 Created: 2012-10-04 Last updated: 2018-06-08Bibliographically approved
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