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Deconvolution of multiple infections in Plasmodium falciparum from high throughput sequencing data

Sha Joe Zhu, Jacob Almagro-Garcia, Gil McVean, Inanc Birol
2017 Bioinformatics  
Advances in protocols and sequencing technology have made it possible to obtain high-coverage genomewide sequencing data from blood samples and blood spots taken in the field.  ...  However, analyzing and interpreting such data is challenging because of the high rate of multiple infections present.  ...  Acknowledgements We thank the Pf3k consortium for valuable insights, in particular, suggestions from Roberto Amato, John O'Brien, Richard Pearson, Jerome Kelleher and Jason Wendler for providing the data  ... 
doi:10.1093/bioinformatics/btx530 pmid:28961721 pmcid:PMC5870807 fatcat:vo6gdyz4mvdclnh5beozpsal2q

Molecular approaches to determine the multiplicity of Plasmodium infections

Daibin Zhong, Cristian Koepfli, Liwang Cui, Guiyun Yan
2018 Malaria Journal  
In this review, the advantages and limitations of current molecular approaches to determine multiplicity of malaria parasite infection are discussed.  ...  Multiplicity of infection (MOI), also termed complexity of infection (COI), is defined as the number of genetically distinct parasite strains co-infecting a single host, which is an important indicator  ...  The computer program has been tested and confirmed to work well for the deconvolution of datasets with a mixture of samples from a single species in P. falciparum [111] .  ... 
doi:10.1186/s12936-018-2322-5 pmid:29685152 pmcid:PMC5914063 fatcat:m7cupoyfzngbhifzsniamcolkm

Advances in omics-based methods to identify novel targets for malaria and other parasitic protozoan infections

Annie N. Cowell, Elizabeth A. Winzeler
2019 Genome Medicine  
A primary method for drug target deconvolution in Plasmodium falciparum is in vitro evolution of compound-resistant parasites followed by whole-genome scans.  ...  Thus, the availability of high-throughput, functional genomic datasets can greatly assist with target deconvolution.  ...  High-throughput genetic validation of targets High-throughput methods such as whole-genome sequencing and proteomics may reveal more than one possible target.  ... 
doi:10.1186/s13073-019-0673-3 pmid:31640748 pmcid:PMC6805675 fatcat:sqzk6xdjvzcdtdafftp7v6dbka

Utilization of genomic sequence information to develop malaria vaccines

D. L. Doolan
2003 Journal of Experimental Biology  
a high-throughput manner.  ...  The decrease in the incidence of P. falciparum infections, the prevalence and density of parasitemia, and the morbidity and mortality associated with Plasmodium spp. infection with natural exposure is  ... 
doi:10.1242/jeb.00615 pmid:14506214 fatcat:yvv6davrgzg4losgq7bjio55he

Plasmodium immunomics

Denise L. Doolan
2011 International Journal of Parasitology  
platforms such as protein arrays, high throughput protein production and epitope prediction algorithms.  ...  The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ~ 5,300 putative proteins. No malaria vaccine has yet been licensed.  ...  Protein microarrays are fabricated using a method involving high throughput amplification of each predicted open reading frame from the genomic sequence using gene-specific primers with adapter sequences  ... 
doi:10.1016/j.ijpara.2010.08.002 pmid:20816843 pmcid:PMC3005034 fatcat:pypdmhsn65dqhmhkprplayz7gi

Stable Expression of a New Chimeric Fluorescent Reporter in the Human Malaria Parasite Plasmodium falciparum

M. Kadekoppala, K. Kline, T. Akompong, K. Haldar
2000 Infection and Immunity  
Stable episomal or integrated expression of GFP has been reported in the rodent malaria parasite Plasmodium berghei (5, 12). However, P. falciparum does not produce stable infection in rodents.  ...  Sequencing the genome of the human malarial parasite Plasmodium falciparum provides a major step forward, but there is a paucity of functional assays to exploit this genetic information.  ...  This work was supported by grants from the NIH (AI 26670, 39073) and a Burroughs Wellcome New Initiatives in Malaria Award to K.H.  ... 
doi:10.1128/iai.68.4.2328-2332.2000 pmid:10722637 pmcid:PMC97421 fatcat:ll5rfncnkzbr3cs43htakoi4zu

Plasmodium Kinases as Potential Drug Targets for Malaria: Challenges and Opportunities

Lauren B Arendse, Susan Wyllie, Kelly Chibale, Ian H Gilbert
2021 ACS Infectious Diseases  
In malaria, several protein kinases are under investigation as potential drug targets, and an inhibitor of Plasmodium phosphatidylinositol 4-kinase type III beta (PI4KIIIβ) is currently in phase 2 clinical  ...  A key challenge in the design of Plasmodium kinase inhibitors is obtaining selectivity over the corresponding human orthologue(s) and other human kinases due to the highly conserved nature of the shared  ...  from infection with P. falciparum.  ... 
doi:10.1021/acsinfecdis.0c00724 pmid:33590753 pmcid:PMC7961706 fatcat:2ob22ikbenddjlnuka3pxylzg4

Antiparasitic Chemotherapy: From Genomes to Mechanisms

David Horn, Manoj T. Duraisingh
2014 Annual Review of Pharmacology and Toxicology  
We review existing drugs and drug development, emphasizing high-throughput genomic and genetic approaches, which hold great promise for elucidating anti-parasitic mechanisms.  ...  We describe the approaches and technologies that have been influential for each parasite and develop some new ideas for future research directions, including strategies for target deconvolution.  ...  Acknowledgments Work in the authors' laboratories is funded by grants from The Wellcome Trust (093010/Z/10/Z and a Senior Investigator Award, 100320/Z/12/Z) to DH and from the National Institutes of Health  ... 
doi:10.1146/annurev-pharmtox-011613-135915 pmid:24050701 pmcid:PMC4381542 fatcat:6h22gi6uzfhjlcr3cisjjrwoa4

Deconvolution of multiple infections inPlasmodium falciparumfrom high throughput sequencing data [article]

Sha Joe Zhu, Jacob Almagro-Garcia, Gil McVean
2017 bioRxiv   pre-print
Advances in protocols and sequencing technology have made it possible to obtain high-coverage genome-wide sequencing data from blood samples and blood spots taken in the field.  ...  However, analysing and interpreting such data is challenging because of the high rate of multiple infections present.  ...  Acknowledgements We thank the Pf3k consortium for valuable insights, in particular, suggestions from Roberto Amato, John O'Brien, Richard Pearson, Jerome Kelleher and Jason Wendler for providing the data  ... 
doi:10.1101/099499 fatcat:fyyeoma7bnbz7alqei4f2v4z3m

Systems analysis of host-parasite interactions

Justine Swann, Neema Jamshidi, Nathan E. Lewis, Elizabeth A. Winzeler
2015 Wiley Interdisciplinary Reviews: Systems Biology and Medicine  
ACKNOWLEDGMENTS We would like to thank members of the Winzeler lab for critical review and discussion of the manuscript.  ...  This work was completed with generous support from the National Institutes for Health, the Bill and Melinda Gates Foundation, The Medicines for Malaria Venture, and the Novo Nordisk Foundation provided  ...  This trend is in part due to technological advancements in the instrumentation and the degree of high-throughput profiling that is feasible for each type of measurement.  ... 
doi:10.1002/wsbm.1311 pmid:26306749 pmcid:PMC4679367 fatcat:krdi3s6pq5exhgeiprsfu34e7q

Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research

Robyn S. Kent, Emma M. Briggs, Beatrice L. Colon, Catalina Alvarez, Sara Silva Pereira, Mariana De Niz
2022 Frontiers in Cellular and Infection Microbiology  
In the age of big data an important question is how to ensure we make the most out of the resources we generate.  ...  In this review, we discuss the major methods used in Apicomplexan and Kinetoplastid research to produce big datasets and advance our understanding of Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma  ...  Dual RNA-seq involves high depth sequencing of transcripts from infected host cells to analyse the host and parasite expression levels simultaneously.  ... 
doi:10.3389/fcimb.2022.900878 pmid:35734575 pmcid:PMC9207352 fatcat:ijakut26wrgx5jmny57csftxbm

Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago [article]

Andrew P Morgan, Nicholas F Brazeau, Billy Ngasala, Lwidiko E. Mhamilawa, Madeline Denton, Mwinyi Msellem, Ulrika Morris, Dayne L Filer, Ozkan Aydemir, Jeffrey A. Bailey, Jonathan Parr, Andreas Mårtensson (+2 others)
2019 bioRxiv   pre-print
sequencing (WGS) to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania.  ...  We assessed ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations by leveraging recent advances in deconvolution of  ...  ACKNOWLEDGEMENTS We would like to thank the communities and participants who took part in these studies. We would also like to thank Molly Deutsch-Feldman for helping to optimize the sWGA protocol. .  ... 
doi:10.1101/863019 fatcat:6jwr3ijworhndh6vd5mgj6awn4

Systems immunology of human malaria

Tuan M. Tran, Babru Samal, Ewen Kirkness, Peter D. Crompton
2012 Trends in Parasitology  
The systems immunology toolbox Human pathogens are detected by cells of the innate immune system (dendritic cells, macrophages, neutrophils, natural killer cells, basophils, eosinophils and mast Review  ...  Germain (National Institute of Allergy and Infectious Diseases, National Institutes of Health) for reading and suggesting changes to the manuscript.  ...  The availability of P. falciparum genome sequence data and high-throughput cloning and in vitro cell-free transcription/translation systems has led to the development of high-density protein microarrays  ... 
doi:10.1016/ pmid:22592005 pmcid:PMC3361535 fatcat:fpcjnfttgnbshfokfsaijyiwbq

Antimalarial Drug Resistance and Implications for the WHO Global Technical Strategy

Matthew M. Ippolito, Kara A. Moser, Jean-Bertin Bukasa Kabuya, Clark Cunningham, Jonathan J. Juliano
2021 Current Epidemiology Reports  
In that time, progress against malaria has plateaued.  ...  More efficient methods for their detection and elaboration have been developed, although low-density infections and polyclonality remain a nuisance to be solved.  ...  in high-transmission regions in sub-Saharan Africa where infections with multiple strains are common.  ... 
doi:10.1007/s40471-021-00266-5 pmid:33747712 pmcid:PMC7955901 fatcat:eupuovyenfe75lrv7clonmvcpi

Muddled mechanisms: recent progress towards antimalarial target identification

Rachel L. Edwards, Audrey R. Odom John
2016 F1000Research  
Plouffe D, Brinker A, McNamara C, et al.: In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen.  ...  Pérez-Moreno G, Cantizani J, Sánchez-Carrasco P, et al.: Discovery of new compounds active against Plasmodium falciparum by high throughput screening of microbial natural products.  ...  Initially, high-throughput screening (HTS) campaigns concentrated on the intraerythrocytic stage of P. falciparum, which resulted in an unprecedented number of hits with the potential to treat the symptomatic  ... 
doi:10.12688/f1000research.9477.1 pmid:27803804 pmcid:PMC5070598 fatcat:4xeakxuyujcjvcgcvzn535kbuu
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