Scientific innovation depends on finding, integrating, and re-using the products of previous research. Here we explore how recent developments in Web technology, particularly those related to the ...publication of data and metadata, might assist that process by providing semantic enhancements to journal articles within the mainstream process of scholarly journal publishing. We exemplify this by describing semantic enhancements we have made to a recent biomedical research article taken from PLoS Neglected Tropical Diseases, providing enrichment to its content and increased access to datasets within it. These semantic enhancements include provision of live DOIs and hyperlinks; semantic markup of textual terms, with links to relevant third-party information resources; interactive figures; a re-orderable reference list; a document summary containing a study summary, a tag cloud, and a citation analysis; and two novel types of semantic enrichment: the first, a Supporting Claims Tooltip to permit "Citations in Context", and the second, Tag Trees that bring together semantically related terms. In addition, we have published downloadable spreadsheets containing data from within tables and figures, have enriched these with provenance information, and have demonstrated various types of data fusion (mashups) with results from other research articles and with Google Maps. We have also published machine-readable RDF metadata both about the article and about the references it cites, for which we developed a Citation Typing Ontology, CiTO (http://purl.org/net/cito/). The enhanced article, which is available at http://dx.doi.org/10.1371/journal.pntd.0000228.x001, presents a compelling existence proof of the possibilities of semantic publication. We hope the showcase of examples and ideas it contains, described in this paper, will excite the imaginations of researchers and publishers, stimulating them to explore the possibilities of semantic publishing for their own research articles, and thereby break down present barriers to the discovery and re-use of information within traditional modes of scholarly communication.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin ...resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.
The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in ...individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax.
Simple Knowledge Organization System (SKOS) provides a data model and vocabulary for expressing Knowledge Organization Systems (KOSs) such as thesauri and classification schemes in Semantic Web ...applications. This paper presents the main components of SKOS and their formal expression in Web Ontology Language (OWL), providing an extensive account of the design decisions taken by the Semantic Web Deployment (SWD) Working Group of the World Wide Web Consortium (W3C), which between 2006 and 2009 brought SKOS to the status of W3C Recommendation. The paper explains key design principles such as “minimal ontological commitment” and systematically cites the requirements and issues that influenced the design of SKOS components.
By reconstructing the discussion around alternative features and design options and presenting the rationale for design decisions, the paper aims at providing insight into how SKOS turned out as it did, and why. Assuming that SKOS, like any other successful technology, may eventually be subject to revision and improvement, the critical account offered here may help future editors approach such a task with deeper understanding.
Abstract
The evolution of insecticide resistance mechanisms in natural populations of Anopheles malaria vectors is a major public health concern across Africa. Using genome sequence data, we study ...the evolution of resistance mutations in the resistance to dieldrin locus (Rdl), a GABA receptor targeted by several insecticides, but most notably by the long-discontinued cyclodiene, dieldrin. The two Rdl resistance mutations (296G and 296S) spread across West and Central African Anopheles via two independent hard selective sweeps that included likely compensatory nearby mutations, and were followed by a rare combination of introgression across species (from A. gambiae and A. arabiensis to A. coluzzii) and across nonconcordant karyotypes of the 2La chromosomal inversion. Rdl resistance evolved in the 1950s as the first known adaptation to a large-scale insecticide-based intervention, but the evolutionary lessons from this system highlight contemporary and future dangers for management strategies designed to combat development of resistance in malaria vectors.
Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale ...multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An. coluzzii from ten locations in West Africa. Resistance was highly multi-genic, multi-allelic and variable between populations. While the strongest and most consistent association with deltamethrin resistance came from Cyp6aa1, this was based on several independent copy number variants (CNVs) in An. coluzzii, and on a non-CNV haplotype in An. gambiae. For pirimiphos-methyl, signals included Ace1, cytochrome P450s, glutathione S-transferases and the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes showed evidence of cross-resistance to both insecticides. These locally-varying, multi-allelic patterns highlight the challenges involved in genomic monitoring of resistance, and may form the basis for improved surveillance methods.
Anopheles coluzzii is a primary vector of malaria found in West and Central Africa, but its presence has hitherto never been documented in Kenya. A thorough understanding of vector bionomics is ...important as it enables the implementation of targeted and effective vector control interventions. Malaria vector surveillance efforts in the country have tended to focus on historically known primary vectors. The current study sought to determine the taxonomic status of samples collected from five different malaria epidemiological zones in Kenya as well as describe the population genetic structure and insecticide resistance profiles in relation to other An. coluzzii populations.
Mosquitoes were sampled as larvae from Busia, Kwale, Turkana, Kirinyaga and Kiambu counties, representing the range of malaria endemicities in Kenya, in 2019 and 2021 and emergent adults analysed using Whole Genome Sequencing (WGS) data processed in accordance with the Anopheles gambiae 1000 Genomes Project phase 3. Where available, historical samples from the same sites were included for WGS. Comparisons were made with An. coluzzii cohorts from West and Central Africa.
This study reports the detection of An. coluzzii for the first time in Kenya. The species was detected in Turkana County across all three time points from which samples were analyzed and its presence confirmed through taxonomic analysis. Additionally, there was a lack of strong population genetic differentiation between An. coluzzii from Kenya and those from the more northerly regions of West and Central Africa, suggesting they represent a connected extension to the known species range. Mutations associated with target-site resistance to DDT and pyrethroids and metabolic resistance to DDT were found at high frequencies up to 64%. The profile and frequencies of the variants observed were similar to An. coluzzii from West and Central Africa but the ace-1 mutation linked to organophosphate and carbamate resistance present in An. coluzzii from coastal West Africa was absent in Kenya.
These findings emphasize the need for the incorporation of genomics in comprehensive and routine vector surveillance to inform on the range of malaria vector species, and their insecticide resistance status to inform the choice of effective vector control approaches.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The emergence of insecticide resistance is a major threat to malaria control programmes in Africa, with many different factors contributing to insecticide resistance in its ...vectors,
Anopheles
mosquitoes.
CYP6M2
has previously been recognized as an important candidate in cytochrome P450-mediated detoxification in
Anopheles
. As it has been implicated in resistance against pyrethroids, organochlorines and carbamates, its broad metabolic activity makes it a potential agent in insecticide cross-resistance. Currently, allelic variation within the
Cyp6m2
gene remains unknown.
Methods
Here, Illumina whole-genome sequence data from Phase 2 of the
Anopheles gambiae
1000 Genomes Project (Ag1000G) was used to examine genetic variation in the
Cyp6m2
gene across 16 populations in 13 countries comprising
Anopheles gambiae
and
Anopheles coluzzii
mosquitoes
.
To identify whether these alleles show evidence of selection either through potentially modified enzymatic function or by being linked to variants that change the transcriptional profile of the gene, hierarchical clustering of haplotypes, linkage disequilibrium, median joining networks and extended haplotype homozygosity analyses were performed.
Results
Fifteen missense biallelic substitutions at high frequency (defined as > 5% frequency in one or more populations) are found, which fall into five distinct haplotype groups that carry the main high frequency variants: A13T, D65A, E328Q, Y347F, I359V and A468S. Despite consistent reports of
Cyp6m2
upregulation and metabolic activity in insecticide resistant Anophelines, no evidence of directional selection is found occurring on these variants or on the haplotype clusters in which they are found.
Conclusion
These results imply that emerging resistance associated with
Cyp6m2
is potentially driven by distant regulatory loci such as transcriptional factors rather than by its missense variants, or that other genes are playing a more significant role in conferring metabolic resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Individual malaria infections can carry multiple strains of
with varying levels of relatedness. Yet, how local epidemiology affects the properties of such mixed infections remains unclear. Here, we ...develop an enhanced method for strain deconvolution from genome sequencing data, which estimates the number of strains, their proportions, identity-by-descent (IBD) profiles and individual haplotypes. Applying it to the Pf3k data set, we find that the rate of mixed infection varies from 29% to 63% across countries and that 51% of mixed infections involve more than two strains. Furthermore, we estimate that 47% of symptomatic dual infections contain sibling strains likely to have been co-transmitted from a single mosquito, and find evidence of mixed infections propagated over successive infection cycles. Finally, leveraging data from the Malaria Atlas Project, we find that prevalence correlates within Africa, but not Asia, with both the rate of mixed infection and the level of IBD.
Diversity at pathogen genetic loci can be driven by host adaptive immune selection pressure and may reveal proteins important for parasite biology. Population-based genome sequencing of Plasmodium ...falciparum, the parasite responsible for the most severe form of malaria, has highlighted two related polymorphic genes called dblmsp and dblmsp2, which encode Duffy binding-like (DBL) domain-containing proteins located on the merozoite surface but whose function remains unknown. Using recombinant proteins and transgenic parasites, we show that DBLMSP and DBLMSP2 directly and avidly bind human IgM via their DBL domains. We used whole genome sequence data from over 400 African and Asian P. falciparum isolates to show that dblmsp and dblmsp2 exhibit extreme protein polymorphism in their DBL domain, with multiple variants of two major allelic classes present in every population tested. Despite this variability, the IgM binding function was retained across diverse sequence representatives. Although this interaction did not seem to have an effect on the ability of the parasite to invade red blood cells, binding of DBLMSP and DBLMSP2 to IgM inhibited the overall immunoreactivity of these proteins to IgG from patients who had been exposed to the parasite. This suggests that IgM binding might mask these proteins from the host humoral immune system.
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