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A statistical approach to finding overlooked genetic associations
Andrew K Rider, Geoffrey Siwo, Nitesh V Chawla, Michael Ferdig, Scott J Emrich
BMC Bioinformatics , 2010, DOI: 10.1186/1471-2105-11-526
Abstract: We propose an alternative method to identify eQTLs that builds on traditional approaches. In contrast to genome-wide techniques, our method determines the significance of an association between an expression trait and a locus with respect to the set of all associations to the expression trait. The use of this specific information facilitates identification of expression traits that have an expression profile that is characterized by a single exceptional association to a locus.Our approach identifies expression traits that have exceptional associations regardless of the genome-wide significance of those associations. This property facilitates the identification of possible false negatives for genome-wide significance. Further, our approach has the property of prioritizing expression traits that are affected by few strong associations. Expression traits identified by this method may warrant additional study because their expression level may be affected by targeting genes near a single locus.We demonstrate our method by identifying eQTL hotspots in Plasmodium falciparum (malaria) and Saccharomyces cerevisiae (yeast). We demonstrate the prioritization of traits with few strong genetic effects through Gene Ontology (GO) analysis of Yeast. Our results are strongly consistent with results gathered using genome-wide methods and identify additional hotspots and eQTLs.New eQTLs and hotspots found with this method may represent regions of the genome or biological processes that are controlled through few relatively strong genetic interactions. These points of interest warrant experimental investigation.eQTL studies use gene expression data and genetic variation between individuals to calculate the association between expression traits and genotypes. In the context of eQTL studies an 'expression trait' refers to the quantity of labeled (c)DNA hybridizing to a single probe on a microarray. An eQTL is a strong association between one locus in the genome and one expression trait.
Shigella in Brazilian children with acute diarrhoea: prevalence, antimicrobial resistance and virulence genes
Sousa, Mireille ?ngela Bernardes;Mendes, Edilberto Nogueira;Collares, Guilherme Birchal;Péret-Filho, Luciano Amedée;Penna, Francisco José;Magalh?es, Paula Prazeres;
Memórias do Instituto Oswaldo Cruz , 2013, DOI: 10.1590/S0074-02762013000100005
Abstract: diarrhoeal disease is still considered a major cause of morbidity and mortality among children. among diarrhoeagenic agents, shigella should be highlighted due to its prevalence and the severity of the associated disease. here, we assessed shigella prevalence, drug susceptibility and virulence factors. faeces from 157 children with diarrhoea who sought treatment at the children's hospital jo?o paulo ii, a reference children′s hospital in belo horizonte, state of minas gerais, brazil, were cultured and drug susceptibility of the shigella isolates was determined by the disk diffusion technique. shigella virulence markers were identified by polymerase chain reaction. the bacterium was recovered from 10.8% of the children (88.2% shigella sonnei). the ipah, iuc, sen and ial genes were detected in strains isolated from all shigellosis patients; set1a was only detected in shigella flexneri. additionally, patients were infected by shigella strains of different ial, sat, sen and set1a genotypes. compared to previous studies, we observed a marked shift in the distribution of species from s. flexneri to s. sonnei and high rates of trimethoprim/sulfamethoxazole resistance.
Characterization of Shigella spp. by antimicrobial resistance and PCR detection of ipa genes in an infantile population from Porto Velho (Western Amazon region), Brazil
Silva, Tatiane;Nogueira, Paulo Afonso;Magalh?es, Gleiciene Félix;Grava, Andréa Fagundes;Silva, Luiz Hildebrando Pereira da;Orlandi, Patrícia Puccinelli;
Memórias do Instituto Oswaldo Cruz , 2008, DOI: 10.1590/S0074-02762008000700017
Abstract: the incidence of shigella spp. was assessed in 877 infants from the public hospital in rond?nia (western amazon region, brazil) where shigella represents the fourth cause of diarrhea. twenty-five isolates were identified: 18 were shigella flexneri, three shigella sonnei, three shigella boydii and one shigella dysenteriae. with the exception of s. dysenteriae, all shigella spp. isolated from children with diarrhea acquired multiple antibiotic resistances. pcr detection of ipa virulence genes and invasion assays of bloody diarrhea and fever (colitis) were compared among 25 patients testing positive for shigella. the ipah and ipabcd genes were detected in almost all isolates and, unsurprisingly, all shigella isolates associated with colitis were able to invade hela cells. this work alerts for multiple antibiotic resistant shigella in the region and characterizes presence of ipa virulence genes and invasion phenotypesin dysenteric shigellosis.
Detection of virulence genes in Malaysian Shigella species by multiplex PCR assay
Kwai Thong, Susan Hoe, SD Puthucheary, Rohani Md Yasin
BMC Infectious Diseases , 2005, DOI: 10.1186/1471-2334-5-8
Abstract: A mPCR assay was designed for the simultaneous detection of chromosomal- and plasmid-encoded virulence genes (set1A, set1B, ial and ipaH) in Shigella spp. One hundred and ten Malaysian strains (1997–2000) isolated from patients from various government hospitals were used. Reproducibility and sensitivity of the assay were also evaluated. Applicability of the mPCR in clinical settings was tested with spiked faeces following preincubation in brain heart infusion (BHI) broth.The ipaH sequence was present in all the strains, while each of the set1A, set1B and ial gene was present in 40% of the strains tested. Reproducibility of the mPCR assay was 100% and none of the non-Shigella pathogens tested in this study were amplified. The mPCR could detect 100 colony-forming units (cfu) of shigellae per reaction mixture in spiked faeces following preincubation.The mPCR system is reproducible, sensitive and is able to identify pathogenic strains of shigellae irrespective of the locality of the virulence genes. It can be easily performed with a high throughput to give a presumptive identification of the causal pathogen.Members of the genus Shigella, namely S. flexneri, S. dysenteriae, S. sonnei and S. boydii have caused and continue to be responsible for mortality and/or morbidity in high risk populations such as children under five years of age, senior citizens, toddlers in day-care centres, patients in custodial institutions, homosexual men and, war- and famine-engulfed people. Yearly episodes of shigellosis globally have been estimated to be 164.7 million and of these, 163.2 million were in developing countries and the remaining in industrialized nations. The mortality rate was approximately 0.7% [1]. A recent study by Lee & Puthucheary [2] on bacterial enteropathogens in childhood diarrhoea in a Malaysian urban hospital showed that Shigella spp. was the third most common bacteria isolated. S. flexneri and S. dysenteriae type 1 infections are usually characterized by frequent pa
Finding Communities of Related Genes  [PDF]
Dennis Wilkinson,Bernardo A. Huberman
Physics , 2002,
Abstract: We present an automated method of identifying communities of functionally related genes from the biomedical literature. These communities encapsulate human gene and protein interactions and identify groups of genes that are complementary in their function. We use graphs to represent the network of gene cooccurrences in articles mentioning particular keywords, and find that these graphs consist of one giant connected component and many small ones. In addition, the vertex degree distribution of the graphs follows a power law, whose exponent we determine. We then use an algorithm based on betweenness centrality to identify community structures within the giant component. The different structures are then aggregated into a final list of communities, whose members are weighted according to how strongly they belong to them. Our method is efficient enough to be applicable to the entire Medline database, and yet the information it extracts is significantly detailed, applicable to a particular problem, and interesting in and of itself. We illustrate the method in the case of colon cancer and demonstrate important features of the resulting communities.
Finding flavor genes
Philippe Reymond
Genome Biology , 2000, DOI: 10.1186/gb-2000-1-2-reports0057
Abstract: Aharoni et al. randomly isolated 1,701 cDNA clones from a strawberry fruit cDNA library and 480 clones from petunia corolla (as control) and printed the PCR-amplified clones on chemically modified glass slides using a robotic device. They used these microarrays to monitor changes in gene expression at three fruit developmental stages (from green to red). Using a rigorous statistical analysis, the authors found that 401 clones were differentially expressed between all three stages, with 177 clones being upregulated between the green and red stages. Sequences of the latter group of genes revealed that more than 50% were related to primary and secondary metabolism. From the other sequences potentially involved in flavor formation, Aharoni et al. identified a novel gene (SAAT) for an alcohol acetyltransferase, an enzyme that catalyzes the final step in the synthesis of volatile esters. This gene shows 16-fold greater expression during the red stage than the green stage of fruit development. The authors expressed recombinant SAAT in Escherichia coli and confirmed that the enzyme has alcohol acetyltransferase activity. Analysis of a series of potential substrates suggests that SAAT is responsible for formation of the predominant esters found in ripe strawberries.Access to Arabidopsis cDNA microarrays is provided by the Arabidopsis Functional Genomics Consortium (AFGC). Links to information on plant microarrays can also be found via the Virtual library: plant-arrays.Large-scale cDNA microarrays are now used with model systems to investigate global patterns of gene expression at the level of the whole organism. The utility of microarrays that cover a restricted portion of the genome, like that described in this paper, will become increasingly recognized, however. This paper is a first example of the use of customized plant cDNA microarrays from a non-model system. It provides a good example of how a small selected array can be used to study a particular developmental proces
Finding the Core-Genes of Chloroplasts  [PDF]
Bassam AlKindy,Jean-Fran?ois Couchot,Christophe Guyeux,Arnaud Mouly,Michel Salomon,Jacques M. Bahi
Computer Science , 2014,
Abstract: Due to the recent evolution of sequencing techniques, the number of available genomes is rising steadily, leading to the possibility to make large scale genomic comparison between sets of close species. An interesting question to answer is: what is the common functionality genes of a collection of species, or conversely, to determine what is specific to a given species when compared to other ones belonging in the same genus, family, etc. Investigating such problem means to find both core and pan genomes of a collection of species, \textit{i.e.}, genes in common to all the species vs. the set of all genes in all species under consideration. However, obtaining trustworthy core and pan genomes is not an easy task, leading to a large amount of computation, and requiring a rigorous methodology. Surprisingly, as far as we know, this methodology in finding core and pan genomes has not really been deeply investigated. This research work tries to fill this gap by focusing only on chloroplastic genomes, whose reasonable sizes allow a deep study. To achieve this goal, a collection of 99 chloroplasts are considered in this article. Two methodologies have been investigated, respectively based on sequence similarities and genes names taken from annotation tools. The obtained results will finally be evaluated in terms of biological relevance.
Finding practical approaches to Integrated Water Resources Management
John Butterworth,Jeroen Warner,Patrick Moriarty,Stef Smits
Water Alternatives , 2010,
Abstract: Integrated Water Resources Management (IWRM) has often been interpreted and implemented in a way that is only really suited to countries with the most developed water infrastructures and management capacities. While sympathetic to many of the criticisms levelled at the IWRM concept and recognising the often disappointing levels of adoption, this paper and the series of papers it introduces identify some alternative ways forward in a developmental context that place more emphasis on the practical in-finding solutions to water scarcity. A range of lighter, more pragmatic and context-adapted approaches, strategies and entry points are illustrated with examples from projects and initiatives in mainly 'developing' countries. The authors argue that a more service-orientated (WASH, irrigation and ecosystem services), locally rooted and balanced approach to IWRM that better matches contexts and capacities should build on such strategies, in addition to the necessary but long-term policy reforms and river basin institution-building at higher levels. Examples in this set of papers not only show that the 'lighter', more opportunistic and incremental approach has potential as well as limitations but also await wider piloting and adoption.
Re-annotation of genome microbial CoDing-Sequences: finding new genes and inaccurately annotated genes
Stéphanie Bocs, Antoine Danchin, Claudine Médigue
BMC Bioinformatics , 2002, DOI: 10.1186/1471-2105-3-5
Abstract: We have developed a new program that automatically identifies biologically significant candidate genes in a bacterial genome. Twenty-six complete prokaryotic genomes were analyzed using this tool, and the accuracy of gene finding was assessed by comparison with existing annotations. This analysis revealed that, despite the enormous effort of genome program annotators, a small but not negligible number of genes annotated within the framework of sequencing projects are likely to be partially inaccurate or plainly wrong. Moreover, the analysis of several putative new genes shows that, as expected, many short genes have escaped annotation. In most cases, these new genes revealed frameshifts that could be either artifacts or genuine frameshifts. Some entirely unexpected new genes have also been identified. This allowed us to get a more complete picture of prokaryotic genomes. The results of this procedure are progressively integrated into the SWISS-PROT reference databank.The results described in the present study show that our procedure is very satisfactory in terms of gene finding accuracy. Except in few cases, discrepancies between our results and annotations provided by individual authors can be accounted for by the nature of each annotation process or by specific characteristics of some genomes. This stresses that close cooperation between scientists, regular update and curation of the findings in databases are clearly required to reduce the level of errors in genome annotation (and hence in reducing the unfortunate spreading of errors through centralized data libraries).The main goal of large-scale genome sequencing projects is to obtain new insights into physiological and biological processes underlying the very organization of life. An essential step in this quest is gene identification, with subsequent functional annotation of the corresponding gene products. Gene recognition in bacteria is far from being always straightforward, despite the fact that bacterial g
Two Cases of Vulvovaginitis Caused by Shigella flexneri and Shigella sonnei: a Case Report
Gül?in Bayramo?lu,Faruk Ayd?n,Gülay Karagüzel,Mustafa ?mamo?lu
Balkan Medical Journal , 2012,
Abstract: Vulvovaginitis caused by Shigella species (Shigella spp.) has rarely been reported. This paper describes two cases of prepubertal vulvovaginitis, presenting with a bloody and purulent vaginal discharge, separately caused by ampicillin-resistant Shigella flexneri and trimethoprim-sulfomethoxazole-resistant Shigella sonnei. Our conclusions are that Shigella spp. is the potential cause of vulvovaginitis in prepubertal girls in developing countries where these pathogens are endemic, and identification of the bacteria and making antibiotic susceptibility testing in these cases should not be overlooked.
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