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41.
Cancer is a heterogeneous disease with different combinations of genetic alterations driving its development in different individuals. We introduce CoMEt, an algorithm to identify combinations of alterations that exhibit a pattern of mutual exclusivity across individuals, often observed for alterations in the same pathway. CoMEt includes an exact statistical test for mutual exclusivity and techniques to perform simultaneous analysis of multiple sets of mutually exclusive and subtype-specific alterations. We demonstrate that CoMEt outperforms existing approaches on simulated and real data. We apply CoMEt to five different cancer types, identifying both known cancer genes and pathways, and novel putative cancer genes.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0700-7) contains supplementary material, which is available to authorized users. 相似文献42.
Faecal pellet counts have been widely used to monitor the abundances of introduced ungulates in New Zealand, but ground-based sampling cannot be conducted safely in the steep non-forest habitats that are common in New Zealand's Southern Alps. Helicopter counts may be an effective technique for monitoring ungulates in steep non-forest habitat. We evaluated the relationship between faecal pellet and helicopter counts of ungulates (primarily feral goat Capra hircus) at 12 non-forest sites in the Southern Alps. Within each site we counted the numbers of ungulates from a helicopter on three occasions and the number of intact faecal pellets along 30 transects. Mean observed densities of feral goats derived from helicopter counts ranged from 0.0 to 20.2 km?2. There was a positive curvilinear (concave down) relationship between faecal pellet and helicopter counts. Compared with faecal pellet counts, helicopter counts were cheaper, could identify ungulate species and provided estimates of absolute density. Helicopter counts are a cost-effective method for monitoring ungulates in the steep non-forest habitats of New Zealand's Southern Alps. 相似文献
43.
Background
Life Science Identifiers (LSIDs) are persistent, globally unique identifiers for biological objects. The decentralised nature of LSIDs makes them attractive for identifying distributed resources. Data of interest to biodiversity researchers (including specimen records, images, taxonomic names, and DNA sequences) are distributed over many different providers, and this community has adopted LSIDs as the identifier of choice. 相似文献44.
M Ozkan SG Desai Y Zhang DM Stevenson J Beane EA White ML Guerinot LR Lynd 《Journal of industrial microbiology & biotechnology》2001,27(5):275-280
Characteristics of 13 newly isolated thermophilic, anaerobic, and cellulolytic strains were compared with previously described
strains of Clostridium thermocellum: ATCC 27405 and JW20 (ATCC 31549). Colony morphology, antibiotic sensitivity, fermentation end-products, and cellulose degradation
were documented. All 13 strains were sensitive to erythromycin (5 μg/ml) and chloramphenicol (25 μg/ml), and all strains but
one were sensitive to kanamycin (20 μg/ml). Polymerase chain reaction (PCR) amplification using primers based on gene sequences
from C. thermocellum ATCC 27405 was successful for all 13 strains in the case of the hydrogenase gene and 11 strains in the case of phosphotransacetylase/acetate
kinase genes. Ten strains amplified a product of the expected size with primers developed to be specific for C. thermocellum 16SrRNA primers. Two of the 13 strains did not amplify any product with the PCR primers designed for the phosphotransacetylase/acetate
kinase and 16SrRNA primers. A MboI-like GATC- recognizing restriction activity was present in all of the five strains examined. The results of this study have
several positive implications with respect to future development of a transformation system for cellulolytic thermophiles.
Journal of Industrial Microbiology & Biotechnology (2001) 27, 275–280.
Received 12 September 2000/ Accepted in revised form 20 November 2000 相似文献
45.
The inclusion complexes of triclosan with native cyclomaltoheptaose (beta-cyclodextrin, betaCD) as well as with negatively and positively charged derivatives are studied. The structure of the inclusion complex betaCD/triclosan in the crystalline state [P1, a=15.189(5), b=15.230(6), c=16.293(6), alpha=91.07(4), beta=91.05(3) gamma=100.71(3)] comprises two crystallographically independent host macrocycles A and B. The packing results in betaCD dimers that align head-to-head and form infinite channels along the c-axis. Only one guest molecule statistically disordered over two positions, (the dichlorophenyl ring in the cavities of either A or B) corresponds to each dimer (a 2:1 host/guest complex). The enclosed dichlorophenyl ring enters the dimer through the primary side, whereas the hydrophilic chlorophenol ring extends in the space between dimers. Water molecules in five positions are also enclosed in the intradimer region, arranged on a plane perpendicular to the sevenfold axis of betaCD. The NMR spectroscopic studies in aqueous solution show the presence of both 1:1 and 2:1 betaCD/triclosan complexes. In the first case, two different 1:1 complexes are simultaneously present, each with either ring entering the narrow primary side of one betaCD molecule. In the 2:1 complex both rings of triclosan are included in two independent betaCD hosts, a precursor to the supramolecular arrangement found in the crystalline form. In the case of the negatively charged sodium heptakis[6-deoxy-6-(3-thiopropionate)]-betaCD, the NMR studies at pH 7.9 show a complete inclusion of triclosan inside the host in two orientations, one for the non-ionized (phenol) and reverse for the ionized (phenolate) form. Finally, for the positively charged heptakis(6-aminoethylamino-6-deoxy)-betaCD, inclusion of triclosan is possible only when the pH is raised to 10 and it is concluded that both aromatic rings are alternatively inside the cavity. However in that case also, inclusion of the entire guest in the elongated cavity is suggested. 相似文献
46.
Jeroen Lakerveld Sandra DM Bot Marijke J Chinapaw Maurits W van Tulder Patricia van Oppen Jacqueline M Dekker Giel Nijpels 《BMC endocrine disorders》2008,8(1):1-11
Background
Insulin resistance and diabetes are associated with increased oxidative stress and impairment of cellular defence systems. Our purpose was to investigate the interaction between glucose metabolism, antioxidative capacity and heat shock protein (HSP) defence in different skeletal muscle phenotypes among middle-aged obese subjects during a long-term exercise and dietary intervention. As a sub-study of the Finnish Diabetes Prevention Study (DPS), 22 persons with impaired glucose tolerance (IGT) taking part in the intervention volunteered to give samples from the vastus lateralis muscle. Subjects were divided into two sub-groups (IGTslow and IGTfast) on the basis of their baseline myosin heavy chain profile. Glucose metabolism, oxidative stress and HSP expressions were measured before and after the 2-year intervention.Results
Exercise training, combined with dietary counselling, increased the expression of mitochondrial chaperones HSP60 and glucose-regulated protein 75 (GRP75) in the vastus lateralis muscle in the IGTslow group and that of HSP60 in the IGTfast group. In cytoplasmic chaperones HSP72 or HSP90 no changes took place. In the IGTslow group, a significant positive correlation between the increased muscle content of HSP60 and the oxygen radical absorbing capacity values and, in the IGTfast group, between the improved VO2max value and the increased protein expression of GRP75 were found. Serum uric acid concentrations decreased in both sub-groups and serum protein carbonyl concentrations decreased in the IGTfast group.Conclusion
The 2-year intervention up-regulated mitochondrial HSP expressions in middle-aged subjects with impaired glucose tolerance. These improvements, however, were not correlated directly with enhanced glucose tolerance. 相似文献47.
Background
Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma.Methods
To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response.Results
We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines.Conclusion
We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2. 相似文献48.
Background
The NCBI taxonomy provides one of the most powerful ways to navigate sequence data bases but currently users are forced to formulate queries according to a single taxonomic classification. Given that there is not universal agreement on the classification of organisms, providing a single classification places constraints on the questions biologists can ask. However, maintaining multiple classifications is burdensome in the face of a constantly growing NCBI classification. 相似文献49.
Cytosolic isocitrate dehydrogenase in humans, mice, and voles and phylogenetic analysis of the enzyme family 总被引:3,自引:0,他引:3
Nekrutenko A; Hillis DM; Patton JC; Bradley RD; Baker RJ 《Molecular biology and evolution》1998,15(12):1674-1684
In this study, we report cDNA sequences of the cytosolic NADP-dependent
isocitrate dehydrogenase for humans, mice, and two species of voles
(Microtus mexicanus and Microtus ochrogaster). Inferred amino acid
sequences from these taxa display a high level of amino acid sequence
conservation, comparable to that of myosin beta heavy chain, and share
known structural features. A Caenorhabditis elegans enzyme that was
previously identified as a protein similar to isocitrate dehydrogenase is
most likely the NADP-dependent cytosolic isocitrate dehydrogenase enzyme
equivalent, based on amino acid similarity to mammalian enzymes and
phylogenetic analysis. We also suggest that NADP-dependent isocitrate
dehydrogenases characterized from alfalfa, soybean, and eucalyptus are most
likely cytosolic enzymes. The phylogenetic tree of various isocitrate
dehydrogenases from eukaryotic sources revealed that independent gene
duplications may have given rise to the cytosolic and mitochondrial forms
of NADP-dependent isocitrate dehydrogenase in animals and fungi. There
appears to be no statistical support for a hypothesis that the
mitochondrial and cytosolic forms of the enzyme are orthologous in these
groups. A possible scenario of the evolution of NADP-dependent isocitrate
dehydrogenases is proposed.
相似文献
50.
Roderic DM Page 《BMC bioinformatics》2007,8(1):158