22 results on '"Lerch, Anita"'
Search Results
2. Projecting vaccine demand and impact for emerging zoonotic pathogens
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Lerch, Anita, ten Bosch, Quirine A., L’Azou Jackson, Maïna, Bettis, Alison A., Bernuzzi, Mauro, Murphy, Georgina A. V., Tran, Quan M., Huber, John H., Siraj, Amir S., Bron, Gebbiena M., Elliott, Margaret, Hartlage, Carson S., Koh, Sojung, Strimbu, Kathyrn, Walters, Magdalene, Perkins, T. Alex, and Moore, Sean M.
- Published
- 2022
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3. Inferring person-to-person networks of Plasmodium falciparum transmission: are analyses of routine surveillance data up to the task?
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Huber, John H., Hsiang, Michelle S., Dlamini, Nomcebo, Murphy, Maxwell, Vilakati, Sibonakaliso, Nhlabathi, Nomcebo, Lerch, Anita, Nielsen, Rasmus, Ntshalintshali, Nyasatu, Greenhouse, Bryan, and Perkins, T. Alex
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- 2022
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4. Impacts of K-12 school reopening on the COVID-19 epidemic in Indiana, USA
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España, Guido, Cavany, Sean, Oidtman, Rachel, Barbera, Carly, Costello, Alan, Lerch, Anita, Poterek, Marya, Tran, Quan, Wieler, Annaliese, Moore, Sean, and Perkins, T. Alex
- Published
- 2021
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5. Estimating unobserved SARS-CoV-2 infections in the United States
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Perkins, T. Alex, Cavany, Sean M., Moore, Sean M., Oidtman, Rachel J., Lerch, Anita, and Poterek, Marya
- Published
- 2020
6. Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and mechanisms for liver-stage differentiation in relapsing malaria
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Muller, Ivo, Jex, Aaron R., Kappe, Stefan H.I., Mikolajczak, Sebastian A., Sattabongkot, Jetsumon, Patrapuvich, Rapatbhorn, Lindner, Scott, Flannery, Erika L., Koepfli, Cristian, Ansell, Brendan, Lerch, Anita, Emery-Corbin, Samantha J., Charnaud, Sarah, Smith, Jeffrey, Merrienne, Nicolas, Swearingen, Kristian E., Moritz, Robert L., Petter, Michaela, Duffy, Michael F., and Chuenchob, Vorada
- Published
- 2019
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7. Plasmodium falciparum transmission in the highlands of Ethiopia is driven by closely related and clonal parasites.
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Holzschuh, Aurel, Ewnetu, Yalemwork, Carlier, Lise, Lerch, Anita, Gerlovina, Inna, Baker, Sarah Cate, Yewhalaw, Delenasaw, Haileselassie, Werissaw, Berhane, Nega, Lemma, Wossenseged, and Koepfli, Cristian
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PLASMODIUM ,PLASMODIUM falciparum ,UPLANDS ,NUCLEOTIDE sequencing ,HUMAN migrations ,PARASITES - Abstract
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]
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- 2024
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8. The Ashbya gossypii Genome as a Tool for Mapping the Ancient Saccharomyces cerevisiae Genome
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Dietrich, Fred S., Voegeli, Sylvia, Brachat, Sophie, Lerch, Anita, Gates, Krista, Steiner, Sabine, Mohr, Christine, Pöhlmann, Rainer, Luedi, Philippe, Choi, Sangdun, Wing, Rod A., Flavier, Albert, Gaffney, Thomas D., and Philippsen, Peter
- Published
- 2004
9. Amplicon deep sequencing improves Plasmodium falciparum genotyping in clinical trials of antimalarial drugs
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Gruenberg, Maria, Lerch, Anita, Beck, Hans-Peter, and Felger, Ingrid
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- 2019
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10. Longitudinal tracking and quantification of individual Plasmodium falciparum clones in complex infections
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Lerch, Anita, Koepfli, Cristian, Hofmann, Natalie E., Kattenberg, Johanna H., Rosanas-Urgell, Anna, Betuela, Inoni, Mueller, Ivo, and Felger, Ingrid
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- 2019
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11. Somatic mutation footprinting reveals a unique tetranucleotide signature associated with intron–exon boundaries in lung cancer
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Wormald, Samuel, Lerch, Anita, Mouradov, Dmitri, and O’Connor, Liam
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- 2018
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12. Methods for analysis of deep sequencing data from mixtures of Plasmodium falciparum clones or stage-specific transcriptomes
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Lerch, Anita, Felger, Ingrid, and Robinson, Mark D.
- Subjects
parasitic diseases - Abstract
Malaria is a life-threatening infectious disease caused by Plasmodium parasites transmitted to humans through bites of infected Anopheles mosquitos. An estimated 445,000 people die every year by an infection with Plasmodium parasites, most of them children living in sub-Saharan Africa. As a result of increased malaria control, the mortality was greatly reduced in the last decades. To develop new tools for elimination and to evaluate the impact of control, a good understanding of the epidemiology and biology of malaria parasites is required. Studies of infection and transmission dynamics of Plasmodium parasites were greatly improved by distinguishing individual parasite clones and monitoring their infection dynamics over time. In regions with high transmission of Plasmodium parasites, individuals are often infected with several clones concurrently. Individual parasites clones can be identified by genotyping. The current standard method used for genotyping is amplification of highly length-polymorphic merozoite surface protein 2 (msp2) or other antigen genes followed by sizing of the amplicon by capillary electrophoresis (CE). The sensitivity to detect low-abundant clones (minority clones) of msp2-CE genotyping is however limited, resulting in an underestimation of multiplicity of infection (MOI). A shortfall of this genotyping method is that frequency of individual clones within a sample cannot be determined. This urges the search for new genotyping methods that rely on sequencing of genomic fragments with extensive single nucleotide polymorphism (SNP). Improvement in next generation sequencing (NGS) technologies permitted the use of amplicon sequencing (Amp-Seq) in epidemiological studies. Genotyping by amplicon sequencing has a higher sensitivity to detect minority clones, can quantify the frequency of each clone within a sample, and allows the use of SNP polymorphic markers. In the frame of this thesis, a new Amp-Seq genotyping assay was developed, including known SNP polymorphic markers, and novel marker ‘cpmp’, as well as a bioinformatic analysis workflow. This genotyping assay was applied on field samples from a longitudinal study conducted in Papua New Guinea. A comparison to msp2-CE genotyping confirmed the higher sensitivity to detect minority clones by Amp-Seq genotyping method and showed a significant underestimation of MOI by classical size polymorphic marker. However, no significant increase in molecular force of infection (molFOI), i.e. number of new infections per individual per year, was observed. Quantification of the frequency of individual clones in longitudinal samples permitted to infer multi-locus haplotypes. Multi-locus haplotypes increased discriminatory power of genotyping and robustly distinguished new infections from those detected in an individual earlier. For calculating the density of clones from multi-clone infections the within-host clone frequency is multiplied by parasitaemia of this infection determined by quantitative PCR. Density of individual parasites clones in multi-clone infections over time is a new parameter for epidemiological studies. It will permit to study the dynamics, and thus fitness, of parasite clones exposed to within-host competition or to acquired natural immunity. NGS also gained great importance in gene expression studies of Plasmodium parasites in patient samples. Transcriptome studies are complicated by the mixture of different developmental stages present concurrently in samples collected from patients. Even in in vitro cultured samples after tight synchronisation or enrichment of a specific developmental stage, small fractions of other development stages are still found. This problem is of particular relevance for P. vivax, as the absence of continuous in vitro culture so far has hampered the study of isolated parasite stages. For example, the transcriptome of P. vivax gametocytes, one of the stages found in peripheral blood and infective to mosquitos, has not yet been described. A solution for differentiating mixed transcription may come from deconvolution methods, which either infer the stage proportion in samples or stage-specific transcriptome signatures. A large selection of different deconvolution methods has been developed for the analysis of heterogeneous tissues, e.g. cancer tissues or hematopoietic cell, but these methods have rarely been applied to mixed stages of malaria parasites. The best suited combination of normalisation and deconvolution methods for analysis of RNA sequencing (RNA-Seq) data from mixed-stage samples of Plasmodium parasites was evaluated based on experimentally mixed highly synchronised blood stages. Normalisation by count per million and deconvolution with a negative binomial regression model followed by selection of genes with significant fold change resulted in the best agreement with transcriptomes as observed in single stages. This strategy can easily be transferred to Plasmodium field samples with known stage proportions. This analysis performed in cultured parasites of defined mixed stages served as proof-of-concept and confirmed that identification of stage-specific genes is feasible also in field samples, notably in species that cannot be cultivated, such as P. vivax. NGS permits fundamentally new approaches to study Plasmodium parasites. This thesis presents a novel marker and data analysis platform for highly sensitive P. falciparum genotyping. Furthermore, a best practice workflow was identified to infer stage-specific gene expression from parasite infections consisting of mixed developmental stages. This provides a crucial tool for the analysis of gene expression data generated from Plasmodium field samples.
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- 2018
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13. Reinvestigation of the Saccharomyces cerevisiae genome annotation by comparison to the genome of a related fungus: Ashbya gossypii
- Author
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Brachat, Sophie, Dietrich, Fred S, Voegeli, Sylvia, Zhang, Zhihong, Stuart, Larissa, Lerch, Anita, Gates, Krista, Gaffney, Tom, and Philippsen, Peter
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- 2003
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14. Development of amplicon deep sequencing markers and data analysis pipeline for genotyping multi-clonal malaria infections.
- Author
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Lerch, Anita, Koepfli, Cristian, Hofmann, Natalie E., Messerli, Camilla, Wilcox, Stephen, Kattenberg, Johanna H., Betuela, Inoni, O'Connor, Liam, Mueller, Ivo, and Felger, Ingrid
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NUCLEOTIDE sequence , *GENOTYPES , *PLASMODIUM falciparum , *DATA analysis , *DRUG efficacy , *CLINICAL trials , *HAPLOTYPES - Abstract
Background: Amplicon deep sequencing permits sensitive detection of minority clones and improves discriminatory power for genotyping multi-clone Plasmodium falciparum infections. New amplicon sequencing and data analysis protocols are needed for genotyping in epidemiological studies and drug efficacy trials of P. falciparum. Methods: Targeted sequencing of molecular marker csp and novel marker cpmp was conducted in duplicate on mixtures of parasite culture strains and 37 field samples. A protocol allowing to multiplex up to 384 samples in a single sequencing run was applied. Software "HaplotypR" was developed for data analysis. Results: Cpmp was highly diverse (He = 0.96) in contrast to csp (He = 0.57). Minority clones were robustly detected if their frequency was >1%. False haplotype calls owing to sequencing errors were observed below that threshold. Conclusions: To reliably detect haplotypes at very low frequencies, experiments are best performed in duplicate and should aim for coverage of >10'000 reads/amplicon. When compared to length polymorphic marker msp2, highly multiplexed amplicon sequencing displayed greater sensitivity in detecting minority clones. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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15. Face Reconstruction from Skull Shapes and Physical Attributes.
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Paysan, Pascal, Lüthi, Marcel, Albrecht, Thomas, Lerch, Anita, Amberg, Brian, Santini, Francesco, and Vetter, Thomas
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Reconstructing a person΄s face from its skeletal remains is a task that has over many decades fascinated artist and scientist alike. In this paper we treat facial reconstruction as a machine learning problem. We use separate statistical shape models to represent the skull and face morphology. We learn the relationship between the parameters of the models by fitting them to a set of MR images of the head and using ridge regression on the resulting model parameters. Since the facial shape is not uniquely defined by the skull shape, we allow to specify target attributes, such as age or weight. Our experiments show that the reconstruction results are generally close to the original face, and that by specifying the right attributes the perceptual and measured difference between the original and the predicted face is reduced. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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16. DNA Sequence Explains Seemingly Disordered Methylation Levels in Partially Methylated Domains of Mammalian Genomes.
- Author
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Gaidatzis, Dimos, Burger, Lukas, Murr, Rabih, Lerch, Anita, Dessus-Babus, Sophie, Schübeler, Dirk, and Stadler, Michael B.
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GENOMICS ,METHYLATION ,NUCLEOTIDE sequence ,CELL lines ,DINUCLEOTIDES ,HUMAN embryonic stem cells - Abstract
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% (R
2 ) 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]- Published
- 2014
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17. QuasR: quantification and annotation of short reads in R.
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Gaidatzis, Dimos, Lerch, Anita, Hahne, Florian, and Stadler, Michael B.
- Abstract
Summary: 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. [ABSTRACT FROM AUTHOR]
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- 2015
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18. Over 100 Years of Rift Valley Fever: A Patchwork of Data on Pathogen Spread and Spillover.
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Bron, Gebbiena M., Strimbu, Kathryn, Cecilia, Hélène, Lerch, Anita, Moore, Sean M., Tran, Quan, Perkins, T. Alex, and ten Bosch, Quirine A.
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RIFT Valley fever ,PATHOGENIC microorganisms ,RUMINANTS ,SEROPREVALENCE ,CULICOIDES ,VIRAL antibodies - Abstract
During the past 100 years, Rift Valley fever virus (RVFV), a mosquito-borne virus, has caused potentially lethal disease in livestock, and has been associated with significant economic losses and trade bans. Spillover to humans occurs and can be fatal. Here, we combined data on RVF disease in humans (22 countries) and animals (37 countries) from 1931 to 2020 with seroprevalence studies from 1950 to 2020 (n = 228) from publicly available databases and publications to draw a more complete picture of the past and current RVFV epidemiology. RVFV has spread from its original locus in Kenya throughout Africa and into the Arabian Peninsula. Throughout the study period seroprevalence increased in both humans and animals, suggesting potentially increased RVFV exposure. In 24 countries, animals or humans tested positive for RVFV antibodies even though outbreaks had never been reported there, suggesting RVFV transmission may well go unnoticed. Among ruminants, sheep were the most likely to be exposed during RVF outbreaks, but not during periods of cryptic spread. We discuss critical data gaps and highlight the need for detailed study descriptions, and long-term studies using a one health approach to further convert the patchwork of data to the tale of RFV epidemiology. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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19. Genetic variations of Plasmodium falciparum circumsporozoite protein and the impact on interactions with human immunoproteins and malaria vaccine efficacy.
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Dieng, Cheikh Cambel, Ford, Colby T., Lerch, Anita, Doniou, Dickson, Vegesna, Kovidh, Janies, Daniel, Cui, Liwang, Amoah, Linda, Afrane, Yaw, and Lo, Eugenia
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- *
CIRCUMSPOROZOITE protein , *MALARIA vaccines , *VACCINE effectiveness , *GENETIC variation , *PLASMODIUM falciparum - Abstract
In October 2021, the world's first malaria vaccine RTS,S was endorsed by WHO for broad use in children, despite its low efficacy. This study examined polyclonal infections and the associations of parasite genetic variations with binding affinity to human leukocyte antigen (HLA). Multiplicity of infection was determined by amplicon deep sequencing of PfMSP1. Genetic variations in PfCSP were examined across 88 samples from Ghana and analyzed together with 1655 PfCSP sequences from other African and non-African isolates. Binding interactions of PfCSP peptide variants and HLA were predicted using NetChop and HADDOCK. High polyclonality was detected among infections, with each infection harboring multiple non-3D7 PfCSP variants. Twenty-seven PfCSP haplotypes were detected in the Ghanaian samples, and they broadly represented PfCSP diversity across Africa. The number of genetic differences between 3D7 and non-3D7 PfCSP variants does not influence binding to HLA. However, CSP peptide length after proteolytic degradation significantly affects its molecular weight and binding affinity to HLA. Despite the high diversity of HLA, the majority of the HLAI and II alleles interacted/bound with all Ghana CSP peptides. Multiple non-3D7 strains among P. falciparum infections could impact the effectiveness of RTS,S. Longer peptides of the Th2R/Th3R CSP regions should be considered in future versions of RTS,S. • The world's first malaria vaccine RTS,S has low efficacy against P. falciparum. • Infections were highly polyclonal each with multiple non-3D7 PfCSP variants. • Genetic differences between 3D7 and non-3D7 PfCSP do not affect binding to HLA. • CSP peptide length significantly affects its binding affinity to the HLA. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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20. The Ashbya gossypii Genome as a Tool for Mapping theAncient Saccharomyces cerevisiae Genome.
- Author
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Dietrich, Fred S., Voegeli, Sylvia, Brachat, Sophie, Lerch, Anita, Gates, Krista, Steiner, Sabine, Mohr, Christine, Pöhlmann, Rainer, Luedi, Philippe, Choi, Sangdun, Wing, Rod A., Flavier, Albert, Gaffney, Thomas D., and Philippsen, Peter
- Subjects
- *
ASHBYA gossypii , *GENETICS , *SACCHAROMYCES cerevisiae , *HEREDITY , *GENOMES , *VITAMIN B complex - Abstract
We have sequenced and annotated the genome of the filamentous ascomycete Ashbya gossypii. With a size of only 9.2 megabases, encoding 4718 protein-coding genes, it is the smallest genome of a free-living eukaryote yet characterized. More than 90% of A. gossypii genes show both homology and a particular pattern of synteny with Saccharomyces cerevisiae. Analysis of this pattern revealed 300 inversions and translocations that have occurred since divergence of these two species. It also provided compelling evidence that the evolution of S. cerevisiae included a whole genome duplication or fusion of two related species and showed, through inferred ancient gene orders, which of the duplicated genes lost one copy and which retained both copies. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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21. Using a mobile nanopore sequencing lab for end-to-end genomic surveillance of Plasmodium falciparum: A feasibility study.
- Author
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Holzschuh A, Lerch A, Fakih BS, Aliy SM, Ali MH, Ali MA, Bruzzese DJ, Yukich J, Hetzel MW, and Koepfli C
- Abstract
Genomic epidemiology holds promise for malaria control and elimination efforts, for example by informing on Plasmodium falciparum genetic diversity and prevalence of mutations conferring anti-malarial drug resistance. Limited sequencing infrastructure in many malaria-endemic areas prevents the rapid generation of genomic data. To address these issues, we developed and validated assays for P. falciparum nanopore sequencing in endemic sites using a mobile laboratory, targeting key antimalarial drug resistance markers and microhaplotypes. Using two multiplexed PCR reactions, we amplified six highly polymorphic microhaplotypes and ten drug resistance markers. We developed a bioinformatics workflow that allows genotyping of polyclonal malaria infections, including minority clones. We validated the panels on mock dried blood spot (DBS) and rapid diagnostic test (RDT) samples and archived DBS, demonstrating even, high read coverage across amplicons (range: 580x to 3,212x median coverage), high haplotype calling accuracy, and the ability to explore within-sample diversity of polyclonal infections. We field-tested the feasibility of rapid genotyping in Zanzibar in close collaboration with the local malaria elimination program using DBS and routinely collected RDTs as sample inputs. Our assay identified haplotypes known to confer resistance to known antimalarials in the dhfr, dhps and mdr1 genes, but no evidence of artemisinin partial resistance. Most infections (60%) were polyclonal, with high microhaplotype diversity (median HE = 0.94). In conclusion, our assays generated actionable data within a few days, and we identified current challenges for implementing nanopore sequencing in endemic countries to accelerate malaria control and elimination., Competing Interests: The authors declare that no competing interests exist., (Copyright: © 2024 Holzschuh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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22. Should Deep-Sequenced Amplicons Become the New Gold Standard for Analyzing Malaria Drug Clinical Trials?
- Author
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Jones S, Kay K, Hodel EM, Gruenberg M, Lerch A, Felger I, and Hastings I
- Subjects
- Humans, Plasmodium falciparum genetics, Antimalarials therapeutic use, Malaria drug therapy, Malaria, Falciparum drug therapy, Pharmaceutical Preparations
- Abstract
Regulatory clinical trials are required to ensure the continued supply and deployment of effective antimalarial drugs. Patient follow-up in such trials typically lasts several weeks, as the drugs have long half-lives and new infections often occur during this period. "Molecular correction" is therefore used to distinguish drug failures from new infections. The current WHO-recommended method for molecular correction uses length-polymorphic alleles at highly diverse loci but is inherently poor at detecting low-density clones in polyclonal infections. This likely leads to substantial underestimates of failure rates, delaying the replacement of failing drugs with potentially lethal consequences. Deep-sequenced amplicons (AmpSeq) substantially increase the detectability of low-density clones and may offer a new "gold standard" for molecular correction. Pharmacological simulation of clinical trials was used to evaluate the suitability of AmpSeq for molecular correction. We investigated the impact of factors such as the number of amplicon loci analyzed, the informatics criteria used to distinguish genotyping "noise" from real low-density signals, the local epidemiology of malaria transmission, and the potential impact of genetic signals from gametocytes. AmpSeq greatly improved molecular correction and provided accurate drug failure rate estimates. The use of 3 to 5 amplicons was sufficient, and simple, nonstatistical criteria could be used to classify recurrent infections as drug failures or new infections. These results suggest AmpSeq is strongly placed to become the new standard for molecular correction in regulatory trials, with potential extension into routine surveillance once the requisite technical support becomes established.
- Published
- 2021
- Full Text
- View/download PDF
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