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21.
22.
Background
The statistical modeling of biomedical corpora could yield integrated, coarse-to-fine views of biological phenomena that complement discoveries made from analysis of molecular sequence and profiling data. Here, the potential of such modeling is demonstrated by examining the 5,225 free-text items in the Caenorhabditis Genetic Center (CGC) Bibliography using techniques from statistical information retrieval. Items in the CGC biomedical text corpus were modeled using the Latent Dirichlet Allocation (LDA) model. LDA is a hierarchical Bayesian model which represents a document as a random mixture over latent topics; each topic is characterized by a distribution over words. 相似文献23.
Background
The shape of phylogenetic trees has been used to make inferences about the evolutionary process by comparing the shapes of actual phylogenies with those expected under simple models of the speciation process. Previous studies have focused on speciation events, but gene duplication is another lineage splitting event, analogous to speciation, and gene loss or deletion is analogous to extinction. Measures of the shape of gene family phylogenies can thus be used to investigate the processes of gene duplication and loss. We make the first systematic attempt to use tree shape to study gene duplication using human gene phylogenies. 相似文献24.
Jorgenson E Tang H Gadde M Province M Leppert M Kardia S Schork N Cooper R Rao DC Boerwinkle E Risch N 《American journal of human genetics》2005,76(2):276-290
Human genetic linkage maps are based on rates of recombination across the genome. These rates in humans vary by the sex of the parent from whom alleles are inherited, by chromosomal position, and by genomic features, such as GC content and repeat density. We have examined--for the first time, to our knowledge--racial/ethnic differences in genetic maps of humans. We constructed genetic maps based on 353 microsatellite markers in four racial/ethnic groups: whites, African Americans, Mexican Americans, and East Asians (Chinese and Japanese). These maps were generated using 9,291 subjects from 2,900 nuclear families who participated in the National Heart, Lung, and Blood Institute-funded Family Blood Pressure Program, the largest sample used for map construction to date. Although the maps for the different groups are generally similar, we did find regional and genomewide differences across ethnic groups, including a longer genomewide map for African Americans than for other populations. Some of this variation was explained by genotyping artifacts--namely, null alleles (i.e., alleles with null phenotypes) at a number of loci--and by ethnic differences in null-allele frequencies. In particular, null alleles appear to be the likely explanation for the excess map length in African Americans. We also found that nonrandom missing data biases map results. However, we found regions on chromosome 8p and telomeric segments with significant ethnic differences and a suggestive interval on chromosome 12q that were not due to genotype artifacts. The difference on chromosome 8p is likely due to a polymorphic inversion in the region. The results of our investigation have implications for inferences of possible genetic influences on human recombination as well as for future linkage studies, especially those involving populations of nonwhite ethnicity. 相似文献
25.
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26.
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27.
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28.
29.
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30.
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