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1.
A diversity of tools is available for identification of variants from genome sequence data. Given the current complexity of incorporating external software into a genome analysis infrastructure, a tendency exists to rely on the results from a single tool alone. The quality of the output variant calls is highly variable however, depending on factors such as sequence library quality as well as the choice of short-read aligner, variant caller, and variant caller filtering strategy. Here we present a two-part study first using the high quality ‘genome in a bottle’ reference set to demonstrate the significant impact the choice of aligner, variant caller, and variant caller filtering strategy has on overall variant call quality and further how certain variant callers outperform others with increased sample contamination, an important consideration when analyzing sequenced cancer samples. This analysis confirms previous work showing that combining variant calls of multiple tools results in the best quality resultant variant set, for either specificity or sensitivity, depending on whether the intersection or union, of all variant calls is used respectively. Second, we analyze a melanoma cell line derived from a control lymphocyte sample to determine whether software choices affect the detection of clinically important melanoma risk-factor variants finding that only one of the three such variants is unanimously detected under all conditions. Finally, we describe a cogent strategy for implementing a clinical variant detection pipeline; a strategy that requires careful software selection, variant caller filtering optimizing, and combined variant calls in order to effectively minimize false negative variants. While implementing such features represents an increase in complexity and computation the results offer indisputable improvements in data quality. 相似文献
2.
Laura De Pretto Stephen Acreman Matthew J. Ashfold Suresh K. Mohankumar Ahimsa Campos-Arceiz 《PloS one》2015,10(12)
Transboundary haze episodes caused by seasonal forest fires have become a recurrent phenomenon in Southeast Asia, with serious environmental, economic, and public health implications. Here we present a cross-sectional survey conducted among people in Kuala Lumpur and surrounds to assess the links between knowledge, attitudes, and practices in relation to the transboundary haze episodes. Of 305 respondents, 125 were amateur athletes participating in a duathlon event and the remainder were surveyed in an inner-city shopping mall. Across the whole sample, people who possessed more factual information about the haze phenomenon showed significantly higher levels of concern. Duathletes were more knowledgeable than non-duathletes and also more concerned about the negative effects of haze, especially on health. For all people who regularly practice outdoor sports (including people interviewed at the shopping mall), higher levels of knowledge and concerned attitudes translated into a greater likelihood of engaging in protective practices, such as cancelling their outdoor training sessions, while those with greater knowledge were more likely to check the relevant air pollution index on a daily basis. Our results indicate that the provision of accurate and timely information about air quality to residents will translate into beneficial practices, at least among particularly exposed individuals, such as amateur athletes who regularly practice outdoor sports. 相似文献
3.
Z. Kato Seiji Fukuda Shunji Tomatsu Hugo Vega Teruo Yasunaga Atsushi Yamagishi Naoto Yamada A. Valencia Luis Alejandro Barrera Kazuko Sukegawa Tadao Orii Naomi Kondo 《Human genetics》1997,101(1):97-101
Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in N-acetylgalactosamine-6-sulfate
sulfatase (GALNS). In previous studies, we have found two common mutations in Caucasians and Japanese, respectively. To characterize
the mutational spectrum in various ethnic groups, mutations in the GALNS gene in Colombian MPS IVA patients were investigated,
and genetic backgrounds were extensively analyzed to identify racial origin, based on mitochondrial DNA (mtDNA) lineages.
Three novel missense mutations never identified previously in other populations and found in 16 out of 19 Colombian MPS IVA
unrelated alleles account for 84.2% of the alleles in this study. The G301C and S162F mutations account for 68.4% and 10.5%
of mutations, respectively, whereas the remaining F69V is limited to a single allele. The skewed prevalence of G301C in only
Colombian patients and haplotype analysis by restriction fragment length polymorphisms in the GALNS gene suggest that G301C
originated from a common ancestor. Investigation of the genetic background by means of mtDNA lineages indicate that all our
patients are probably of native American descent.
Received: 2 January 1997 / Accepted: 10 June 1997 相似文献
4.
Whereas the left atrial appendage plays a rather minor role under physiological circumstances, it gains an importance in patients with atrial fibrillation. Compelling evidence has revealed that the left atrial appendage is implicated as the source of thrombus in the vast majority of strokes in atrial fibrillation. Oral anticoagulation remains the standard of care for stroke prevention in atrial fibrillation; nevertheless, this treatment has several limitations and is often contraindicated, particularly in the elderly population in whom the risk of stroke is high. Therefore, occluding the left atrial appendage is a logical approach to prevent thrombus formation and subsequent cardioembolic events in these patients. We present a review of clinical outcomes of patients with atrial fibrillation undergoing left atrial appendage closure and the challenges faced in this field. 相似文献
5.
6.
Minh H. Dinh Meegan R. Anderson Michael D. McRaven Gianguido C. Cianci Scott G. McCoombe Z. L. Kelley Casey J. Gioia Angela J. Fought Alfred W. Rademaker Ronald S. Veazey Thomas J. Hope 《PLoS pathogens》2015,11(3)
To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/− 0.0154 and 0.0171 +/− 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/− 0.0079 virions/image) than glans tissue (0.0167 +/− 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/− 0.0188 vs. 0.0151 +/− 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/− 3.908 vs. 12.466 +/− 2.985 μm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men. 相似文献
7.
8.
A modified oligodeoxyribonucleotide duplex containing an unnatural internucleotide trisubstituted 3' to 5' pyrophosphate bond in one strand [5'(oligo1)3'-P(OCH3)P-5'(oligo2) 3'] reacts with nucleophiles in aqueous media by acting as a phosphorylating affinity reagent. When interacted with a protein, a portion of the oligonucleotide [--P-5'(oligo2)3'] becomes attached to an amino acid nucleophilic group through a phosphate of the O-methyl-modified pyrophosphate linkage. We demonstrate the affinity labeling of nucleophilic groups at the active sites of the EcoRI and RsrI restriction and modification enzymes with an oligodeoxyribonucleotide duplex containing a modified scissile bond in the EcoRI recognition site. With the EcoRI and RsrI endonucleases in molar excess approximately 1% of the oligonucleotide becomes attached to the protein, and with the companion methyltransferases the yield approaches 40% for the EcoRI enzyme and 30% for the RsrI methyltransferase. Crosslinking proceeds only upon formation of a sequence-specific enzyme-DNA complex, and generates a covalent bond between the 3'-phosphate of the modified pyrophosphate in the substrate and a nucleophilic group at the active site of the enzyme. The reaction results in the elimination of an oligodeoxyribonucleotide remnant that contains the 3'-O-methylphosphate [5'(oligo1)3'-P(OCH3)] derived from the modified phosphate of the pyrophosphate linkage. Hydrolysis properties of the covalent protein-DNA adducts indicate that phosphoamide (P-N) bonds are formed with the EcoRI endonuclease and methyltransferase. 相似文献
9.
Anthony E. Kincaid Kathryn F. Hudson Matthew W. Richey Jason C. Bartz 《Journal of virology》2012,86(23):12731-12740
Prion infection and pathogenesis are dependent on the agent crossing an epithelial barrier to gain access to the recipient nervous system. Several routes of infection have been identified, but the mechanism(s) and timing of in vivo prion transport across an epithelium have not been determined. The hamster model of nasal cavity infection was used to determine the temporal and spatial parameters of prion-infected brain homogenate uptake following inhalation and to test the hypothesis that prions cross the nasal mucosa via M cells. A small drop of infected or uninfected brain homogenate was placed below each nostril, where it was immediately inhaled into the nasal cavity. Regularly spaced tissue sections through the entire extent of the nasal cavity were processed immunohistochemically to identify brain homogenate and the disease-associated isoform of the prion protein (PrPd). Infected or uninfected brain homogenate was identified adhering to M cells, passing between cells of the nasal mucosa, and within lymphatic vessels of the nasal cavity at all time points examined. PrPd was identified within a limited number of M cells 15 to 180 min following inoculation, but not in the adjacent nasal mucosa-associated lymphoid tissue (NALT). While these results support M cell transport of prions, larger amounts of infected brain homogenate were transported paracellularly across the respiratory, olfactory, and follicle-associated epithelia of the nasal cavity. These results indicate that prions can immediately cross the nasal mucosa via multiple routes and quickly enter lymphatics, where they can spread systemically via lymph draining the nasal cavity. 相似文献
10.
O. B. Flekhter L. T. Karachurina V. V. Poroikov L. P. Nigmatullina L. A. Baltina F. S. Zarudii V. A. Davydova L. V. Spirikhin I. P. Baikova F. Z. Galin G. A. Tolstikov 《Russian Journal of Bioorganic Chemistry》2000,26(3):192-200
Hemisuccinates, hemiphthalates, acetylsalicylates, cinnamates, andp-methoxycinnamates of lupeol, betulin, and 3-O-acetylbetulin were synthesized via interaction with corresponding acid anhydrides or acid chlorides. A number of betulin
esters in position 3 and 28 were shown to exhibit a pronounced hepatoprotective effect similar to that of betulin and silibor.
These experimental data were in a good agreement with the computer prediction of their biological activity. Betulin 3,28-bishemiphthalate
was more effective than carsil in models of experimental hepatitis caused by carbon tetrachloride, tetracycline, and ethanol. 相似文献