| 11. |
- Bannasch, Danika, et al.
(författare)
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Localization of canine brachycephaly using an across breed mapping approach
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9632-
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Tidskriftsartikel (refereegranskat)abstract
- The domestic dog, Canis familiaris, exhibits profound phenotypic diversity and is an ideal model organism for the genetic dissection of simple and complex traits. However, some of the most interesting phenotypes are fixed in particular breeds and are therefore less tractable to genetic analysis using classical segregation-based mapping approaches. We implemented an across breed mapping approach using a moderately dense SNP array, a low number of animals and breeds carefully selected for the phenotypes of interest to identify genetic variants responsible for breed-defining characteristics. Using a modest number of affected (10-30) and control (20-60) samples from multiple breeds, the correct chromosomal assignment was identified in a proof of concept experiment using three previously defined loci; hyperuricosuria, white spotting and chondrodysplasia. Genome-wide association was performed in a similar manner for one of the most striking morphological traits in dogs: brachycephalic head type. Although candidate gene approaches based on comparable phenotypes in mice and humans have been utilized for this trait, the causative gene has remained elusive using this method. Samples from nine affected breeds and thirteen control breeds identified strong genome-wide associations for brachycephalic head type on Cfa 1. Two independent datasets identified the same genomic region. Levels of relative heterozygosity in the associated region indicate that it has been subjected to a selective sweep, consistent with it being a breed defining morphological characteristic. Genotyping additional dogs in the region confirmed the association. To date, the genetic structure of dog breeds has primarily been exploited for genome wide association for segregating traits. These results demonstrate that non-segregating traits under strong selection are equally tractable to genetic analysis using small sample numbers.
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| 12. |
- Barrio, Alvaro Martinez, et al.
(författare)
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Targeted Resequencing and Analysis of the Diamond-Blackfan Anemia Disease Locus RPS19
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6172-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Ribosomal protein S19 gene locus (RPS19) has been linked to two kinds of red cell aplasia, Diamond-Blackfan Anemia (DBA) and Transient Erythroblastopenia in Childhood (TEC). Mutations in RPS19 coding sequences have been found in 25% of DBA patients, but not in TEC patients. It has been suggested that non-coding RPS19 sequence variants contribute to the considerable clinical variability in red cell aplasia. We therefore aimed at identifying non-coding variations associated with DBA or TEC phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: We targeted a region of 19'980 bp encompassing the RPS19 gene in a cohort of 89 DBA and TEC patients for resequencing. We provide here a catalog of the considerable, previously unrecognized degree of variation in this region. We identified 73 variations (65 SNPs, 8 indels) that all are located outside of the RPS19 open reading frame, and of which 67.1% are classified as novel. We hypothesize that specific alleles in non-coding regions of RPS19 could alter the binding of regulatory proteins or transcription factors. Therefore, we carried out an extensive analysis to identify transcription factor binding sites (TFBS). A series of putative interaction sites coincide with detected variants. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). CONCLUSIONS: Specific alleles at predicted TFBSs may alter the expression of RPS19, modify an important interaction between transcription factors with overlapping TFBS or remove an important stimulus for hematopoiesis. We suggest that the detected interactions are of importance for hematopoiesis and could provide new insights into individual response to treatment.
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| 13. |
- Barrio, Alvaro Martinez, et al.
(författare)
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The First Sequenced Carnivore Genome Shows Complex Host-Endogenous Retrovirus Relationships
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5, s. e19832-
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Tidskriftsartikel (refereegranskat)abstract
- Host-retrovirus interactions influence the genomic landscape and have contributed substantially to mammalian genome evolution. To gain further insights, we analyzed a female boxer (Canis familiaris) genome for complexity and integration pattern of canine endogenous retroviruses (CfERV). Intriguingly, the first such in-depth analysis of a carnivore species identified 407 CfERV proviruses that represent only 0.15% of the dog genome. In comparison, the same detection criteria identified about six times more HERV proviruses in the human genome that has been estimated to contain a total of 8% retroviral DNA including solitary LTRs. These observed differences in man and dog are likely due to different mechanisms to purge, restrict and protect their genomes against retroviruses. A novel group of gammaretrovirus-like CfERV with high similarity to HERV-Fc1 was found to have potential for active retrotransposition and possibly lateral transmissions between dog and human as a result of close interactions during at least 10.000 years. The CfERV integration landscape showed a non-uniform intra-and inter-chromosomal distribution. Like in other species, different densities of ERVs were observed. Some chromosomal regions were essentially devoid of CfERVs whereas other regions had large numbers of integrations in agreement with distinct selective pressures at different loci. Most CfERVs were integrated in antisense orientation within 100 kb from annotated protein-coding genes. This integration pattern provides evidence for selection against CfERVs in sense orientation relative to chromosomal genes. In conclusion, this ERV analysis of the first carnivorous species supports the notion that different mammals interact distinctively with endogenous retroviruses and suggests that retroviral lateral transmissions between dog and human may have occurred.
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| 14. |
- Beisvåg, Vidar, et al.
(författare)
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Contributions of the EMERALD project to assessing and improving microarray data quality
- 2011
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Ingår i: BioTechniques. - : Future Science Ltd. - 0736-6205 .- 1940-9818. ; 50:1, s. 27-31
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Tidskriftsartikel (refereegranskat)abstract
- While minimum information about a microarray experiment (MIAME) standards have helped to increase the value of the microarray data deposited into public databases like ArrayExpress and Gene Expression Omnibus (GEO), limited means have been available to assess the quality of this data or to identify the procedures used to normalize and transform raw data. The EMERALD FP6 Coordination Action was designed to deliver approaches to assess and enhance the overall quality of microarray data and to disseminate these approaches to the microarray community through an extensive series of workshops, tutorials, and symposia. Tools were developed for assessing data quality and used to demonstrate how the removal of poor-quality data could improve the power of statistical analyses and facilitate analysis of multiple joint microarray data sets. These quality metrics tools have been disseminated through publications and through the software package arrayQualityMetrics. Within the framework provided by the Ontology of Biomedical Investigations, ontology was developed to describe data transformations, and software ontology was developed for gene expression analysis software. In addition, the consortium has advocated for the development and use of external reference standards in microarray hybridizations and created the Molecular Methods (MolMeth) database, which provides a central source for methods and protocols focusing on microarray-based technologies.
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| 15. |
- Benachenhou, Farid, et al.
(författare)
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Conserved structure and inferred evolutionary history of long terminal repeats (LTRs)
- 2013
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Ingår i: Mobile DNA. - : Springer Science and Business Media LLC. - 1759-8753. ; 4, s. 5-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long terminal repeats (LTRs, consisting of U3-R-U5 portions) are important elements of retroviruses and related retrotransposons. They are difficult to analyse due to their variability. The aim was to obtain a more comprehensive view of structure, diversity and phylogeny of LTRs than hitherto possible. Results: Hidden Markov models (HMM) were created for 11 clades of LTRs belonging to Retroviridae (class III retroviruses), animal Metaviridae (Gypsy/Ty3) elements and plant Pseudoviridae (Copia/Ty1) elements, complementing our work with Orthoretrovirus HMMs. The great variation in LTR length of plant Metaviridae and the few divergent animal Pseudoviridae prevented building HMMs from both of these groups. Animal Metaviridae LTRs had the same conserved motifs as retroviral LTRs, confirming that the two groups are closely related. The conserved motifs were the short inverted repeats (SIRs), integrase recognition signals (5' TGTTRNR ... YNYAACA 3'); the polyadenylation signal or AATAAA motif; a GT-rich stretch downstream of the polyadenylation signal; and a less conserved AT-rich stretch corresponding to the core promoter element, the TATA box. Plant Pseudoviridae LTRs differed slightly in having a conserved TATA-box, TATATA, but no conserved polyadenylation signal, plus a much shorter R region. The sensitivity of the HMMs for detection in genomic sequences was around 50% for most models, at a relatively high specificity, suitable for genome screening. The HMMs yielded consensus sequences, which were aligned by creating an HMM model (a 'Superviterbi' alignment). This yielded a phylogenetic tree that was compared with a Pol-based tree. Both LTR and Pol trees supported monophyly of retroviruses. In both, Pseudoviridae was ancestral to all other LTR retrotransposons. However, the LTR trees showed the chromovirus portion of Metaviridae clustering together with Pseudoviridae, dividing Metaviridae into two portions with distinct phylogeny. Conclusion: The HMMs clearly demonstrated a unitary conserved structure of LTRs, supporting that they arose once during evolution. We attempted to follow the evolution of LTRs by tracing their functional foundations, that is, acquisition of RNAse H, a combined promoter/polyadenylation site, integrase, hairpin priming and the primer binding site (PBS). Available information did not support a simple evolutionary chain of events.
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| 16. |
- Bongcam Rudloff, Erik
(författare)
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2013 Annual General Meeting: Executive Board Report
- 2013
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Ingår i: EMBnet.journal. - 2226-6089. ; 19.1, s. 24-25
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- During the past year, the Executive Board (EB) met regularly and held frequent meetings with the Operational Board via Skype. These meetings allowed discussion of a range of issues relating to the Project Committees (PCs), to EMBnet.journal, to the website, the Stichting accounts, membership, etc. In alternate months, we also endeavoured to convene Skype meetings open to the full EMBnet constituency; however, for larger numbers of attendees, technical issues continued to cause problems. Attempting to address these issues, we took the first steps towards evaluating the various tools and technologies available for online meetings, by creating a list of existing tools, and a protocol on how to test them. The test will be realised in the same spirit as the ‘ping project1' of the ‘80s. The 2013 AGM allowed us to convene a working group to discuss the issues in more detail, and to initiate a common experiment with different software and different Nodes. The ultimate goal is to write a white paper and to publish the results in EMBnet.journal. The last year has been both busy and productive, building substantially on the programme of work we outlined in 2010. In particular, working closely with Itico2 to improve the EMBnet ‘brand', we finally launched the new website, which now includes a new online fee-payment module for individual members. We call on all members to help augment the content of the new site and to help keep it up-to-date. Since the 2012 AGM in Uppsala, EMBnet's training strategy has been dominated by our leadership of GOBLET3 (the Global Organisation for Bioinformatics Learning, Education and Training), which has been established as a Stichting, registered in the Netherlands, following the successful model of EMBnet. Working through GOBLET has significantly increased our level of interaction and cooperation with a range of major international societies and networks (including ISCB4, ASBCB5,ISB6, APBioNet7, SoIBio8, ABN9 and so on) - from the original 10 members who signed the Memorandum of Understanding to establish GOBLET, a further 16 organisations and several individuals have committed to join the Foundation. Another profound advance for EMBnet this year has been the final ratification of the new statutes, which were voted in during the Uppsala 2012 AGM - these statutes became legally binding in April 2013. The most significant result of the change is that we are now able formally to accept individual members (this allows, say, former Node managers to join, or any individual to participate in EMBnet's activities but whose organisation is not a member). Since ratification of the statutes, we have already had several membership applications, and welcomed one new organisation; new memberships will be processed without delay via the online payment system. The new statutes also ushered in changes to the internal structure of the organisation, obliging the PC Chairs and the EB to work together much more closely than they have done in the past; it has also allowed us to streamline the way in which EMBnet's activities
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| 17. |
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| 18. |
- Bongcam Rudloff, Erik
(författare)
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2016 EMBnet Annual General Meeting – Executive Board Report
- 2017
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Ingår i: EMBnet.journal. - : EMBnet Stichting. - 2226-6089. ; 22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- During the past year, the Executive Board (EB) held regular monthly meetings either via Skype or using Adobe Connect. These meetings were carried out with the Interim Board (IB), comprising members of the EB and Teresa Attwood and Etienne de Villiers. The IB was established during the 2015 Annual General Meeting (AGM) both to support the new EB in its first steps forward (as three of its members were new), and to help oversee implementation and delivery of the investment strategy. The EB also regularly invited Special Interest Group (SIG) Chairs to participate at EB-IB meetings. Additional monthly meetings open to the full EMBnet constituency were also convened. In this report, we provide a brief overview of activities and achievements from June 2015 to October 2016.
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| 19. |
- Bongcam Rudloff, Erik
(författare)
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2nd Combined Working Group and Management Committee Meeting of Urine and Kidney Proteomics COST Action 29-30 March 2009, Nafplio, Greece
- 2009
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Ingår i: PROTEOMICS - Clinical Applications. - : Wiley. - 1862-8346 .- 1862-8354. ; 3, s. 1017-1022
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Tidskriftsartikel (refereegranskat)abstract
- EuroKUP (Urine and Kidney Proteomics; www.eurokup.org) is a COST (European Cooperation in the field of Scientific and Technical research: www.cost.esf.org Action fostering amulti-disciplinary network of investigators from 25 countries and focusing on facilitating translational proteomic research in kidney diseases. Four Working Groups focusing respectively on defining clinically important research questions in kidney diseases, kidney tissue proteomics, urine proteomics and bioinformatics have been generated. The EuroKUP members had their second combined Working Group and Management Committee (MC) meeting in Nafplio, Greece from March 29 to 30, 2009. This report summarizes the main presentations, discussions and agreed action points during this meeting. These refer to the design of collaborative projects and clinical center networks for specific kidney diseases; establishment of guidelines for kidney tissue proteomics analysis by laser-based imaging- and laser capture microdissection-MS; development and characterization of a "standard" urine specimen to be used for assessment of platform capability and data comparability in clinical proteomics applications; definition of statistical requirements in biomarker discovery studies; and development of a specialized kidney and urine ontology. Various training activities are planned involving training schools on laser capture microdissection-and imaging-MS, workshops on ontologies as well as short-term travel grants for junior investigators.
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| 20. |
- Bongcam Rudloff, Erik
(författare)
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Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action
- 2023
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Ingår i: Frontiers in Microbiology. - 1664-302X. ; 14
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Forskningsöversikt (refereegranskat)abstract
- The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish "gold standard" protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory 'omics' features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices.
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