| 1. |
- Emery, Samantha J., et al.
(författare)
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Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis
- 2018
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Ingår i: GigaScience. - : OXFORD UNIV PRESS. - 2047-217X. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metronidazole (Mtz) is the frontline drug treatment for multiple anaerobic pathogens, including the gastrointestinal protist, Giardia duodenalis. However, treatment failure is common and linked to in vivo drug resistance. In Giardia, in vitro drug-resistant lines allow controlled experimental interrogation of resistance mechanisms in isogenic cultures. However, resistance-associated changes are inconsistent between lines, phenotypic data are incomplete, and resistance is rarely genetically fixed, highlighted by reversion to sensitivity after drug selection ceases or via passage through the life cycle. Comprehensive quantitative approaches are required to resolve isolate variability, fully define Mtz resistance phenotypes, and explore the role of post-translational modifications therein. Findings: We performed quantitative proteomics to describe differentially expressed proteins in 3 seminal Mtz-resistant lines compared to their isogenic, Mtz-susceptible, parental line. We also probed changes in post-translational modifications including protein acetylation, methylation, ubiquitination, and phosphorylation via immunoblotting. We quantified more than 1,000 proteins in each genotype, recording substantial genotypic variation in differentially expressed proteins between isotypes. Our data confirm substantial changes in the antioxidant network, glycolysis, and electron transport and indicate links between protein acetylation and Mtz resistance, including cross-resistance to deacetylase inhibitor trichostatin A in Mtz-resistant lines. Finally, we performed the first controlled, longitudinal study of Mtz resistance stability, monitoring lines after cessation of drug selection, revealing isolate-dependent phenotypic plasticity. Conclusions: Our data demonstrate understanding that Mtz resistance must be broadened to post-transcriptional and post-translational responses and that Mtz resistance is polygenic, driven by isolate-dependent variation, and is correlated with changes in protein acetylation networks.
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| 2. |
- Gaser, Christian, et al.
(författare)
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CAT : a computational anatomy toolbox for the analysis of structural MRI data
- 2024
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Ingår i: GigaScience. - : Oxford University Press. - 2047-217X. ; 13, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- A large range of sophisticated brain image analysis tools have been developed by the neuroscience community, greatly advancing the field of human brain mapping. Here we introduce the Computational Anatomy Toolbox (CAT)-a powerful suite of tools for brain morphometric analyses with an intuitive graphical user interface but also usable as a shell script. CAT is suitable for beginners, casual users, experts, and developers alike, providing a comprehensive set of analysis options, workflows, and integrated pipelines. The available analysis streams-illustrated on an example dataset-allow for voxel-based, surface-based, and region-based morphometric analyses. Notably, CAT incorporates multiple quality control options and covers the entire analysis workflow, including the preprocessing of cross-sectional and longitudinal data, statistical analysis, and the visualization of results. The overarching aim of this article is to provide a complete description and evaluation of CAT while offering a citable standard for the neuroscience community.
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| 3. |
- Olsen, Remi-Andre, et al.
(författare)
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De novo assembly of Dekkera bruxellensis : a multi technology approach using short and long-read sequencing and optical mapping
- 2015
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: It remains a challenge to perform de novo assembly using next-generation sequencing (NGS). Despite the availability of multiple sequencing technologies and tools (e.g., assemblers) it is still difficult to assemble new genomes at chromosome resolution (i.e., one sequence per chromosome). Obtaining high quality draft assemblies is extremely important in the case of yeast genomes to better characterise major events in their evolutionary history. The aim of this work is two-fold: on the one hand we want to show how combining different and somewhat complementary technologies is key to improving assembly quality and correctness, and on the other hand we present a de novo assembly pipeline we believe to be beneficial to core facility bioinformaticians. To demonstrate both the effectiveness of combining technologies and the simplicity of the pipeline, here we present the results obtained using the Dekkera bruxellensis genome. Methods: In this work we used short-read Illumina data and long-read PacBio data combined with the extreme long-range information from OpGen optical maps in the task of de novo genome assembly and finishing. Moreover, we developed NouGAT, a semi-automated pipeline for read-preprocessing, de novo assembly and assembly evaluation, which was instrumental for this work. Results: We obtained a high quality draft assembly of a yeast genome, resolved on a chromosomal level. Furthermore, this assembly was corrected for mis-assembly errors as demonstrated by resolving a large collapsed repeat and by receiving higher scores by assembly evaluation tools. With the inclusion of PacBio data we were able to fill about 5 % of the optical mapped genome not covered by the Illumina data.
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| 4. |
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| 5. |
- Tedersoo, Leho, et al.
(författare)
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Standardizing metadata and taxonomic identification in metabarcoding studies
- 2015
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X .- 2047-217X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput sequencing-based metabarcoding studies produce vast amounts of ecological data, but a lack of consensus on standardization of metadata and how to refer to the species recovered severely hampers reanalysis and comparisons among studies. Here we propose an automated workflow covering data submission, compression, storage and public access to allow easy data retrieval and inter-study communication. Such standardized and readily accessible datasets facilitate data management, taxonomic comparisons and compilation of global metastudies.
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| 6. |
- Vasicek, Jakub, et al.
(författare)
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Finding haplotypic signatures in proteins
- 2023
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The nonrandom distribution of alleles of common genomic variants produces haplotypes, which are fundamental in medical and population genetic studies. Consequently, protein-coding genes with different co-occurring sets of alleles can encode different amino acid sequences: protein haplotypes. These protein haplotypes are present in biological samples and detectable by mass spectrometry, but they are not accounted for in proteomic searches. Consequently, the impact of haplotypic variation on the results of proteomic searches and the discoverability of peptides specific to haplotypes remain unknown. Findings: Here, we study how common genetic haplotypes influence the proteomic search space and investigate the possibility to match peptides containing multiple amino acid substitutions to a publicly available data set of mass spectra. We found that for 12.42% of the discoverable amino acid substitutions encoded by common haplotypes, 2 or more substitutions may co-occur in the same peptide after tryptic digestion of the protein haplotypes. We identified 352 spectra that matched to such multivariant peptides, and out of the 4,582 amino acid substitutions identified, 6.37% were covered by multivariant peptides. However, the evaluation of the reliability of these matches remains challenging, suggesting that refined error rate estimation procedures are needed for such complex proteomic searches. Conclusions: As these procedures become available and the ability to analyze protein haplotypes increases, we anticipate that proteomics will provide new information on the consequences of common variation, across tissues and time.
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| 7. |
- Wu, L., et al.
(författare)
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The global catalogue of microorganisms 10K type strain sequencing project: closing the genomic gaps for the validly published prokaryotic and fungi species
- 2018
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Genomic information is essential for taxonomic, phylogenetic, and functional studies to comprehensively decipher the characteristics of microorganisms, to explore microbiomes through metagenomics, and to answer fundamental questions of nature and human life. However, large gaps remain in the available genomic sequencing information published for bacterial and archaeal species, and the gaps are even larger for fungal type strains. The Global Catalogue of Microorganisms (GCM) leads an internationally coordinated effort to sequence type strains and close gaps in the genomic maps of microorganisms. Hence, the GCM aims to promote research by deep-mining genomic data.
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