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21.
Accuracy of haplotype reconstruction from haplotype-tagging single-nucleotide polymorphisms
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Forton J Kwiatkowski D Rockett K Luoni G Kimber M Hull J 《American journal of human genetics》2005,76(3):438-448
Many investigators are now using haplotype-tagging single-nucleotide polymorphism (htSNPs) as a way of screening regions of the genome for association with disease. A common approach is to genotype htSNPs in a study population and to use this information to draw inferences about each individual's haplotypic makeup, including SNPs that were not directly genotyped. To test the validity of this approach, we simulated the exercise of typing htSNPs in a large sample of individuals and compared the true and inferred haplotypes. The accuracy of haplotype inference varied, depending on the method of selecting htSNPs, the linkage-disequilibrium structure of the region, and the amount of missing data. At the stage of selection of htSNPs, haplotype-block-based methods required a larger number of htSNPs than did unstructured methods but gave lower levels of error in haplotype inference, particularly when there was a significant amount of missing data. We present a Web-based utility that allows investigators to compare the likely error rates of different sets of htSNPs and to arrive at an economical set of htSNPs that provides acceptable levels of accuracy in haplotype inference. 相似文献
22.
Brian?DM?TomEmail author Walter?R?Gilks Elizabeth?T?Brooke-Powell James?W?Ajioka 《BMC bioinformatics》2005,6(1):234
Background
A common feature of microarray experiments is the occurence of missing gene expression data. These missing values occur for a variety of reasons, in particular, because of the filtering of poor quality spots and the removal of undefined values when a logarithmic transformation is applied to negative background-corrected intensities. The efficiency and power of an analysis performed can be substantially reduced by having an incomplete matrix of gene intensities. Additionally, most statistical methods require a complete intensity matrix. Furthermore, biases may be introduced into analyses through missing information on some genes. Thus methods for appropriately replacing (imputing) missing data and/or weighting poor quality spots are required. 相似文献23.
Background
The taxonomic name of an organism is a key link between different databases that store information on that organism. However, in the absence of a single, comprehensive database of organism names, individual databases lack an easy means of checking the correctness of a name. Furthermore, the same organism may have more than one name, and the same name may apply to more than one organism. 相似文献24.
SMM?VerstappenEmail author AR?Poole M?Ionescu LE?King M?Abrahamowicz DM?Hofman JWJ?Bijlsma FPJG?Lafeber the Utrecht Rheumatoid Arthritis Cohort Study group 《Arthritis research & therapy》2005,8(1):R31
Introduction
The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA). 相似文献25.
Dunstan SJ Nguyen TH Rockett K Forton J Morris AP Diakite M Mai NL Le TP House D Parry CM Ha V Nguyen TH Dougan G Tran TH Kwiatowski D Farrar JJ 《Human genetics》2007,122(1):51-61
The genomic region surrounding the TNF locus on human chromosome 6 has previously been associated with typhoid fever in Vietnam (Dunstan et al. in J Infect Dis
183:261–268, 2001). We used a haplotypic approach to understand this association further. Eighty single nucleotide polymorphisms (SNPs) spanning
a 150 kb region were genotyped in 95 Vietnamese individuals (typhoid case/mother/father trios). A subset of data from 33 SNPs
with a minor allele frequency of >4.3% was used to construct haplotypes. Fifteen SNPs, which tagged the 42 constructed haplotypes
were selected. The haplotype tagging SNPs (T1–T15) were genotyped in 380 confirmed typhoid cases and 380 Vietnamese ethnically
matched controls. Allelic frequencies of seven SNPs (T1, T2, T3, T5, T6, T7, T8) were significantly different between typhoid
cases and controls. Logistic regression results support the hypothesis that there is just one signal associated with disease
at this locus. Haplotype-based analysis of the tag SNPs provided positive evidence of association with typhoid (posterior
probability 0.821). The analysis highlighted a low-risk cluster of haplotypes that each carry the minor allele of T1 or T7,
but not both, and otherwise carry the combination of alleles *12122*1111 at T1–T11, further supporting the one associated
signal hypothesis. Finally, individuals that carry the typhoid fever protective haplotype *12122*1111 also produce a relatively
low TNF-α response to LPS. 相似文献
26.
27.
Viktorian Miok Saskia M Wilting Mark A van de Wiel Annelieke Jaspers Paula I van Noort Ruud H Brakenhoff Peter JF Snijders Renske DM Steenbergen Wessel N van Wieringen 《BMC bioinformatics》2014,15(1)
Background
To determine which changes in the host cell genome are crucial for cervical carcinogenesis, a longitudinal in vitro model system of HPV-transformed keratinocytes was profiled in a genome-wide manner. Four cell lines affected with either HPV16 or HPV18 were assayed at 8 sequential time points for gene expression (mRNA) and gene copy number (DNA) using high-resolution microarrays. Available methods for temporal differential expression analysis are not designed for integrative genomic studies.Results
Here, we present a method that allows for the identification of differential gene expression associated with DNA copy number changes over time. The temporal variation in gene expression is described by a generalized linear mixed model employing low-rank thin-plate splines. Model parameters are estimated with an empirical Bayes procedure, which exploits integrated nested Laplace approximation for fast computation. Iteratively, posteriors of hyperparameters and model parameters are estimated. The empirical Bayes procedure shrinks multiple dispersion-related parameters. Shrinkage leads to more stable estimates of the model parameters, better control of false positives and improvement of reproducibility. In addition, to make estimates of the DNA copy number more stable, model parameters are also estimated in a multivariate way using triplets of features, imposing a spatial prior for the copy number effect.Conclusion
With the proposed method for analysis of time-course multilevel molecular data, more profound insight may be gained through the identification of temporal differential expression induced by DNA copy number abnormalities. In particular, in the analysis of an integrative oncogenomics study with a time-course set-up our method finds genes previously reported to be involved in cervical carcinogenesis. Furthermore, the proposed method yields improvements in sensitivity, specificity and reproducibility compared to existing methods. Finally, the proposed method is able to handle count (RNAseq) data from time course experiments as is shown on a real data set.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-327) contains supplementary material, which is available to authorized users. 相似文献28.
Ribosomal RNA secondary structure: compensatory mutations and implications for phylogenetic analysis 总被引:6,自引:0,他引:6
Using sequence data from the 28S ribosomal RNA (rRNA) genes of selected
vertebrates, we investigated the effects that constraints imposed by
secondary structure have on the phylogenetic analysis of rRNA sequence
data. Our analysis indicates that characters from both base-pairing regions
(stems) and non-base-pairing regions (loops) contain phylogenetic
information, as judged by the level of support of the phylogenetic results
compared with a well-established tree based on both morphological and
molecular data. The best results (the greatest level of support of
well-accepted nodes) were obtained when the complete data set was used.
However, some previously supported nodes were resolved using either the
stem or loop bases alone. Stem bases sustain a greater number of
compensatory mutations than would be expected at random, but the number is
< 40% of that expected under a hypothesis of perfect compensation to
maintain secondary structure. Therefore, we suggest that in phylogenetic
analyses, the weighting of stem characters be reduced by no more than 20%,
relative to that of loop characters. In contrast to previous suggestions,
we do not recommend weighting of stem positions by one-half, compared with
that of loop positions, because this overcompensates for the constraints
that selection imposes on the secondary structure of rRNA.
相似文献
29.
Clara Correia‐Melo Francisco DM Marques Rhys Anderson Graeme Hewitt Rachael Hewitt John Cole Bernadette M Carroll Satomi Miwa Jodie Birch Alina Merz Michael D Rushton Michelle Charles Diana Jurk Stephen WG Tait Rafal Czapiewski Laura Greaves Glyn Nelson Mohammad Bohlooly‐Y Sergio Rodriguez‐Cuenca Antonio Vidal‐Puig Derek Mann Gabriele Saretzki Giovanni Quarato Douglas R Green Peter D Adams Thomas von Zglinicki Viktor I Korolchuk João F Passos 《The EMBO journal》2016,35(7):724-742
30.
Hemocyte-mediated melanization of microfilariae in Aedes aegypti 总被引:1,自引:0,他引:1
The melanization response of adult female Aedes aegypti (black-eyed Liverpool strain) against intrathoracically inoculated Dirofilaria immitis microfilariae (mff) was assessed with transmission electron microscopy. The initial reaction involved the lysis of hemocytes at or near the surface of the parasite prior to the deposition of pigment. Subsequently, melanin formation was noted in the area of lysed cells and appeared to cascade onto the parasite surface. Observations suggest that melanin may be synthesized within certain hemocytes and released by exocytosis or upon cell lysis. Intact and disrupted nuclei and cytoplasmic elements from lysed hemocytes became numerous as mff became completely coated with melanin. A double membrane-like structure formed around the melanized mff and cellular debris during the later stages of the reaction, which eventually isolated the melanin capsule from hemolymph components. Results obtained are discussed in relation to the melanization response previously described for Aedes trivittatus. 相似文献