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  • 1
    In: Nature, Springer Science and Business Media LLC, Vol. 450, No. 7169 ( 2007-11), p. 560-565
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2007
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2007
    In:  BMC Bioinformatics Vol. 8, No. 1 ( 2007-12)
    In: BMC Bioinformatics, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2007-12)
    Abstract: The translational efficiency of an mRNA can be modulated by upstream open reading frames (uORFs) present in certain genes. A uORF can attenuate translation of the main ORF by interfering with translational reinitiation at the main start codon. uORFs also occur by chance in the genome, in which case they do not have a regulatory role. Since the sequence determinants for functional uORFs are not understood, it is difficult to discriminate functional from spurious uORFs by sequence analysis. Results We have used comparative genomics to identify novel uORFs in yeast with a high likelihood of having a translational regulatory role. We examined uORFs, previously shown to play a role in regulation of translation in Saccharomyces cerevisiae , for evolutionary conservation within seven Saccharomyces species. Inspection of the set of conserved uORFs yielded the following three characteristics useful for discrimination of functional from spurious uORFs: a length between 4 and 6 codons, a distance from the start of the main ORF between 50 and 150 nucleotides, and finally a lack of overlap with, and clear separation from, neighbouring uORFs. These derived rules are inherently associated with uORFs with properties similar to the GCN4 locus, and may not detect most uORFs of other types. uORFs with high scores based on these rules showed a much higher evolutionary conservation than randomly selected uORFs. In a genome-wide scan in S. cerevisiae , we found 34 conserved uORFs from 32 genes that we predict to be functional; subsequent analysis showed the majority of these to be located within transcripts. A total of 252 genes were found containing conserved uORFs with properties indicative of a functional role; all but 7 are novel. Functional content analysis of this set identified an overrepresentation of genes involved in transcriptional control and development. Conclusion Evolutionary conservation of uORFs in yeasts can be traced up to 100 million years of separation. The conserved uORFs have certain characteristics with respect to length, distance from each other and from the main start codon, and folding energy of the sequence. These newly found characteristics can be used to facilitate detection of other conserved uORFs.
    Type of Medium: Online Resource
    ISSN: 1471-2105
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2007
    detail.hit.zdb_id: 2041484-5
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2004
    In:  Bioinformatics Vol. 20, No. 18 ( 2004-12-12), p. 3628-3635
    In: Bioinformatics, Oxford University Press (OUP), Vol. 20, No. 18 ( 2004-12-12), p. 3628-3635
    Abstract: Summary: A set of new algorithms and software tools for automatic protein identification using peptide mass fingerprinting is presented. The software is automatic, fast and modular to suit different laboratory needs, and it can be operated either via a Java user interface or called from within scripts. The software modules do peak extraction, peak filtering and protein database matching, and communicate via XML. Individual modules can therefore easily be replaced with other software if desired, and all intermediate results are available to the user. The algorithms are designed to operate without human intervention and contain several novel approaches. The performance and capabilities of the software is illustrated on spectra from different mass spectrometer manufacturers, and the factors influencing successful identification are discussed and quantified. Motivation: Protein identification with mass spectrometric methods is a key step in modern proteomics studies. Some tools are available today for doing different steps in the analysis. Only a few commercial systems integrate all the steps in the analysis, often for only one vendor's hardware, and the details of these systems are not public. Results: A complete system for doing protein identification with peptide mass fingerprints is presented, including everything from peak picking to matching the database protein. The details of the different algorithms are disclosed so that academic researchers can have full control of their tools. Availability: The described software tools are available from the Halmstad University website www.hh.se/staff/bioinf/ Supplementary information: Details of the algorithms are described in supporting information available from the Halmstad University website www.hh.se/staff/bioinf/
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2004
    detail.hit.zdb_id: 1468345-3
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2006
    In:  Bioinformatics Vol. 22, No. 5 ( 2006-03-01), p. 517-522
    In: Bioinformatics, Oxford University Press (OUP), Vol. 22, No. 5 ( 2006-03-01), p. 517-522
    Abstract: Motivation: Analyses of genomic signatures are gaining attention as they allow studies of species-specific relationships without involving alignments of homologous sequences. A naïve Bayesian classifier was built to discriminate between different bacterial compositions of short oligomers, also known as DNA words. The classifier has proven successful in identifying foreign genes in Neisseria meningitis. In this study we extend the classifier approach using either a fixed higher order Markov model (Mk) or a variable length Markov model (VLMk). Results: We propose a simple algorithm to lock a variable length Markov model to a certain number of parameters and show that the use of Markov models greatly increases the flexibility and accuracy in prediction to that of a naïve model. We also test the integrity of classifiers in terms of false-negatives and give estimates of the minimal sizes of training data. We end the report by proposing a method to reject a false hypothesis of horizontal gene transfer. Availability: Software and Supplementary information available at Contact:  dalevi@cs.chalmers.se
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1468345-3
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2010
    In:  Bioinformatics Vol. 26, No. 3 ( 2010-02-01), p. 295-301
    In: Bioinformatics, Oxford University Press (OUP), Vol. 26, No. 3 ( 2010-02-01), p. 295-301
    Abstract: Motivation: Shotgun sequencing generates large numbers of short DNA reads from either an isolated organism or, in the case of metagenomics projects, from the aggregate genome of a microbial community. These reads are then assembled based on overlapping sequences into larger, contiguous sequences (contigs). The feasibility of assembly and the coverage achieved (reads per nucleotide or distinct sequence of nucleotides) depend on several factors: the number of reads sequenced, the read length and the relative abundances of their source genomes in the microbial community. A low coverage suggests that most of the genomic DNA in the sample has not been sequenced, but it is often difficult to estimate either the extent of the uncaptured diversity or the amount of additional sequencing that would be most efficacious. In this work, we regard a metagenome as a population of DNA fragments (bins), each of which may be covered by one or more reads. We employ a gamma distribution to model this bin population due to its flexibility and ease of use. When a gamma approximation can be found that adequately fits the data, we may estimate the number of bins that were not sequenced and that could potentially be revealed by additional sequencing. We evaluated the performance of this model using simulated metagenomes and demonstrate its applicability on three recent metagenomic datasets. Contact:  sean.d.hooper@genpat.uu.se Supplementary information:  Supplementary data are available at Bioinformatics online.
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 6
    In: Systematic Reviews, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2021-12)
    Abstract: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. To decrease the high case fatality rates and morbidity for sepsis and septic shock, there is a need to increase the accuracy of early detection of suspected sepsis in prehospital and emergency department settings. This may be achieved by developing risk prediction decision support systems based on artificial intelligence. Methods The overall aim of this scoping review is to summarize the literature on existing methods for early detection of sepsis using artificial intelligence. The review will be performed using the framework formulated by Arksey and O’Malley and further developed by Levac and colleagues. To identify primary studies and reviews that are suitable to answer our research questions, a comprehensive literature collection will be compiled by searching several sources. Constrictions regarding time and language will have to be implemented. Therefore, only studies published between 1 January 1990 and 31 December 2020 will be taken into consideration, and foreign language publications will not be considered, i.e., only papers with full text in English will be included. Databases/web search engines that will be used are PubMed, Web of Science Platform, Scopus, IEEE Xplore, Google Scholar, Cochrane Library, and ACM Digital Library. Furthermore, clinical studies that have completed patient recruitment and reported results found in the database ClinicalTrials.gov will be considered. The term artificial intelligence is viewed broadly, and a wide range of machine learning and mathematical models suitable as base for decision support will be evaluated. Two members of the team will test the framework on a sample of included studies to ensure that the coding framework is suitable and can be consistently applied. Analysis of collected data will provide a descriptive summary and thematic analysis. The reported results will convey knowledge about the state of current research and innovation for using artificial intelligence to detect sepsis in early phases of the medical care chain. Ethics and dissemination The methodology used here is based on the use of publicly available information and does not need ethical approval. It aims at aiding further research towards digital solutions for disease detection and health innovation. Results will be extracted into a review report for submission to a peer-reviewed scientific journal. Results will be shared with relevant local and national authorities and disseminated in additional appropriate formats such as conferences, lectures, and press releases.
    Type of Medium: Online Resource
    ISSN: 2046-4053
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2662257-9
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  • 7
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2002
    In:  Journal of Molecular Evolution Vol. 55, No. 1 ( 2002-7-1), p. 24-36
    In: Journal of Molecular Evolution, Springer Science and Business Media LLC, Vol. 55, No. 1 ( 2002-7-1), p. 24-36
    Type of Medium: Online Resource
    ISSN: 0022-2844 , 1432-1432
    Language: Unknown
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2002
    detail.hit.zdb_id: 1464309-1
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  • 8
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2009
    In:  Nucleic Acids Research Vol. 37, No. 7 ( 2009-04-01), p. 2096-2104
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 37, No. 7 ( 2009-04-01), p. 2096-2104
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2009
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Public Library of Science (PLoS) ; 2008
    In:  PLoS ONE Vol. 3, No. 7 ( 2008-7-9), p. e2607-
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  • 10
    In: Molecular Cancer, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2013-12)
    Abstract: Neuroblastoma (NB) tumours are commonly divided into three cytogenetic subgroups. However, by unsupervised principal components analysis of gene expression profiles we recently identified four distinct subgroups, r1-r4. In the current study we characterized these different subgroups in more detail, with a specific focus on the fourth divergent tumour subgroup (r4). Methods Expression microarray data from four international studies corresponding to 148 neuroblastic tumour cases were subject to division into four expression subgroups using a previously described 6-gene signature. Differentially expressed genes between groups were identified using Significance Analysis of Microarray (SAM). Next, gene expression network modelling was performed to map signalling pathways and cellular processes representing each subgroup. Findings were validated at the protein level by immunohistochemistry and immunoblot analyses. Results We identified several significantly up-regulated genes in the r4 subgroup of which the tyrosine kinase receptor ERBB3 was most prominent (fold change: 132–240). By gene set enrichment analysis (GSEA) the constructed gene network of ERBB3 (n = 38 network partners) was significantly enriched in the r4 subgroup in all four independent data sets. ERBB3 was also positively correlated to the ErbB family members EGFR and ERBB2 in all data sets, and a concurrent overexpression was seen in the r4 subgroup. Further studies of histopathology categories using a fifth data set of 110 neuroblastic tumours, showed a striking similarity between the expression profile of r4 to ganglioneuroblastoma (GNB) and ganglioneuroma (GN) tumours. In contrast, the NB histopathological subtype was dominated by mitotic regulating genes, characterizing unfavourable NB subgroups in particular. The high ErbB3 expression in GN tumour types was verified at the protein level, and showed mainly expression in the mature ganglion cells. Conclusions Conclusively, this study demonstrates the importance of performing unsupervised clustering and subtype discovery of data sets prior to analyses to avoid a mixture of tumour subtypes, which may otherwise give distorted results and lead to incorrect conclusions. The current study identifies ERBB3 as a clear-cut marker of a GNB/GN-like expression profile, and we suggest a 7-gene expression signature (including ERBB3 ) as a complement to histopathology analysis of neuroblastic tumours. Further studies of ErbB3 and other ErbB family members and their role in neuroblastic differentiation and pathogenesis are warranted.
    Type of Medium: Online Resource
    ISSN: 1476-4598
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2091373-4
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