Biomedical subjects

Ole F Christensen

Publications and source records attributed to Ole F Christensen.

4 recordsLinked to original sources

PubMed2006

Pseudo-likelihood for non-reversible nucleotide substitution models with neighbour dependent rates.

In the field of molecular evolution genome substitution models with neighbour dependent substitution rates have recently received much attention. It is well-known that substitution of nucleotides does not occur independently of neighbouring nucleotides, but there has been less focus on the phenomenon that this substitution process is also not time-reversible. In this paper I construct a pseudo-likelihood type method for inference in non-reversible substitution models with neighbour dependent substitution rates. I also construct an EM-algorithm for maximising the pseudo-likelihood. For human-mouse aligned sequence data a number of different models are investigated, where I show that strand-symmetric models are appropriate, and that overlapping di-nucleotide models do not fit the data well.

Algorithms↗

PubMed2005

Pigs in sequence space: a 0.66X coverage pig genome survey based on shotgun sequencing.

BACKGROUND: Comparative whole genome analysis of Mammalia can benefit from the addition of more species. The pig is an obvious choice due to its economic and medical importance as well as its evolutionary position in the artiodactyls. RESULTS: We have generated approximately 3.84 million shotgun sequences (0.66X coverage) from the pig genome. The data are hereby released (NCBI Trace repository with center name "SDJVP", and project name "Sino-Danish Pig Genome Project") together with an initial evolutionary analysis. The non-repetitive fraction of the sequences was aligned to the UCSC human-mouse alignment and the resulting three-species alignments were annotated using the human genome annotation. Ultra-conserved elements and miRNAs were identified. The results show that for each of these types of orthologous data, pig is much closer to human than mouse is. Purifying selection has been more efficient in pig compared to human, but not as efficient as in mouse, and pig seems to have an isochore structure most similar to the structure in human. CONCLUSION: The addition of the pig to the set of species sequenced at low coverage adds to the understanding of selective pressures that have acted on the human genome by bisecting the evolutionary branch between human and mouse with the mouse branch being approximately 3 times as long as the human branch. Additionally, the joint alignment of the shot-gun sequences to the human-mouse alignment offers the investigator a rapid way to defining specific regions for analysis and resequencing.

Animals↗

PubMed2005

Pseudo-likelihood analysis of codon substitution models with neighbor-dependent rates.

Recently, Markov processes for the evolution of coding DNA with neighbor dependence in the instantaneous substitution rates have been considered. The neighbor dependency makes the models analytically intractable, and previously Markov chain Monte Carlo methods have been used for statistical inference. Using a pseudo-likelihood idea, we introduce in this paper an approximative estimation method which is fast to compute. The pseudo-likelihood estimates are shown to be very accurate, and from analyzing 348 human-mouse coding sequences we conclude that the incorporation of a CpG effect improves the fit of the model considerably.

Algorithms↗

PubMed2002

Bayesian prediction of spatial count data using generalized linear mixed models.

Spatial weed count data are modeled and predicted using a generalized linear mixed model combined with a Bayesian approach and Markov chain Monte Carlo. Informative priors for a data set with sparse sampling are elicited using a previously collected data set with extensive sampling. Furthermore, we demonstrate that so-called Langevin-Hastings updates are useful for efficient simulation of the posterior distributions, and we discuss computational issues concerning prediction.

Agriculture↗