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Unlabelled: QuasR is a package for the integrated analysis of high-throughput sequencing data in R, covering all steps from read preprocessing, alignment and quality control to quantification. QuasR supports different experiment types (including RNA-seq, ChIP-seq and Bis-seq) and analysis variants (e.g. paired-end, stranded, spliced and allele-specific), and is integrated in Bioconductor so that its output can be directly processed for statistical analysis and visualization., Availability and Implementation: QuasR is implemented in R and C/C++. Source code and binaries for major platforms (Linux, OS X and MS Windows) are available from Bioconductor (www.bioconductor.org/packages/release/bioc/html/QuasR.html). The package includes a 'vignette' with step-by-step examples for typical work flows., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2014. Published by Oxford University Press.)

Malaria cases are frequently recorded in the Ethiopian highlands even at altitudes above 2000 m. The epidemiology of malaria in the Ethiopian highlands, and, in particular, the role of importation by human migration from the highly endemic lowlands is not well understood. We sequenced 187 Plasmodium falciparum samples from two sites in the Ethiopian highlands, Gondar (n = 159) and Ziway (n = 28), using a multiplexed droplet digital PCR (ddPCR)‐based amplicon sequencing method targeting 35 microhaplotypes and drug resistance loci. Here, we characterize the parasite population structure and genetic relatedness. We identify moderate parasite diversity (mean HE: 0.54) and low infection complexity (74.9% monoclonal). A significant percentage of infections share microhaplotypes, even across transmission seasons and sites, indicating persistent local transmission. We identify multiple clusters of clonal or near‐clonal infections, highlighting high genetic relatedness. Only 6.3% of individuals diagnosed with P. falciparum reported recent travel. Yet, in clonal or near‐clonal clusters, infections of travellers were frequently observed first in time, suggesting that parasites may have been imported and then transmitted locally. 31.1% of infections are pfhrp2‐deleted and 84.4% pfhrp3‐deleted, and 28.7% have pfhrp2/3 double deletions. Parasites with pfhrp2/3 deletions and wild‐type parasites are genetically distinct. Mutations associated with resistance to sulphadoxine–pyrimethamine or suggested to reduce sensitivity to lumefantrine are observed at near‐fixation. In conclusion, genomic data corroborate local transmission and the importance of intensified control in the Ethiopian highlands. [ABSTRACT FROM AUTHOR]

For the most part metazoan genomes are highly methylated and harbor only small regions with low or absent methylation. In contrast, partially methylated domains (PMDs), recently discovered in a variety of cell lines and tissues, do not fit this paradigm as they show partial methylation for large portions (20%–40%) of the genome. While in PMDs methylation levels are reduced on average, we found that at single CpG resolution, they show extensive variability along the genome outside of CpG islands and DNase I hypersensitive sites (DHS). Methylation levels range from 0% to 100% in a roughly uniform fashion with only little similarity between neighboring CpGs. A comparison of various PMD-containing methylomes showed that these seemingly disordered states of methylation are strongly conserved across cell types for virtually every PMD. Comparative sequence analysis suggests that DNA sequence is a major determinant of these methylation states. This is further substantiated by a purely sequence based model which can predict 31% (R2) of the variation in methylation. The model revealed CpG density as the main driving feature promoting methylation, opposite to what has been shown for CpG islands, followed by various dinucleotides immediately flanking the CpG and a minor contribution from sequence preferences reflecting nucleosome positioning. Taken together we provide a reinterpretation for the nucleotide-specific methylation levels observed in PMDs, demonstrate their conservation across tissues and suggest that they are mainly determined by specific DNA sequence features. [ABSTRACT FROM AUTHOR]