Mining Filarial Genomes for Diagnostic and Therapeutic Targets

Bennuru, Sasisekhar; O’Connell, Elise M.; Drame, Papa M.; Nutman, Thomas B.

doi:10.1016/j.pt.2017.09.003

Cited by 18 publications

(14 citation statements)

References 125 publications

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“…New data and technologies have promised to speed the discovery and validation of novel therapeutic targets. The release of the B. malayi draft genome initiated a wave of target-based approaches that leverage genomic data, molecular biology, and rational target selection, which allow for the cloning, expression, and screening of putative targets in recombinant systems or exploring the repurposing of approved drugs with known targets [10][11][12][13]. Intrinsic to this process is the assumption that the desired transcript and isoform of a given target is known and amenable to straightforward cloning.…”

Section: Introductionmentioning

confidence: 99%

Long-read RNA sequencing of human and animal filarial parasites improves gene models and discovers operons

2020

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Filarial parasitic nematodes (Filarioidea) cause substantial disease burden to humans and animals around the world. Recently there has been a coordinated global effort to generate, annotate, and curate genomic data from nematode species of medical and veterinary importance. This has resulted in two chromosome-level assemblies (Brugia malayi and Onchocerca volvulus) and 11 additional draft genomes from Filarioidea. These reference assemblies facilitate comparative genomics to explore basic helminth biology and prioritize new drug and vaccine targets. While the continual improvement of genome contiguity and completeness advances these goals, experimental functional annotation of genes is often hindered by poor gene models. Short-read RNA sequencing data and expressed sequence tags, in cooperation with ab initio prediction algorithms, are employed for gene prediction, but these can result in missing clade-specific genes, fragmented models, imperfect mapping of gene ends, and lack of isoform resolution. Long-read RNA sequencing can overcome these drawbacks and greatly improve gene model quality. Here, we present Iso-Seq data for B. malayi and Dirofilaria immitis, etiological agents of lymphatic filariasis and canine heartworm disease, respectively. These data cover approximately half of the known coding genomes and substantially improve gene models by extending untranslated regions, cataloging novel splice junctions from novel isoforms, and correcting mispredicted junctions. Furthermore, we validated computationally predicted operons, manually curated new operons, and merged fragmented gene models. We carried out analyses of poly(A) tails in both species, leading to the identification of non-canonical poly(A) signals. Finally, we prioritized and assessed known and putative anthelmintic targets, correcting or validating gene models for molecular cloning and target-based anthelmintic screening efforts. Overall, these data significantly improve the catalog of gene models for two important parasites, and they demonstrate how long-read RNA sequencing should be prioritized for ongoing improvement of parasitic nematode genome assemblies.

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Section: Introductionmentioning

confidence: 99%

Long-read RNA sequencing of human and animal filarial parasites improves gene models and discovers operons

2020

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“…For example, several approaches are being employed to identify targets for onchocerciasis serological assays to support programmatic decision-making. 8–11 These efforts should be expanded to include other NTDs. In particular, promising new epitope screening technologies may help to accelerate the identification of novel targets and permutations of targets for serological assays.…”

Section: New Scientific Opportunitiesmentioning

confidence: 99%

Diagnostics and the neglected tropical diseases roadmap: setting the agenda for 2030

Souza

Ducker

Argaw

et al. 2020

Transactions of the Royal Society of Tropical Medicine and Hygiene

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Accurate and reliable diagnostic tools are an essential requirement for neglected tropical diseases (NTDs) programmes. However, the NTD community has historically underinvested in the development and improvement of diagnostic tools, potentially undermining the successes achieved over the last 2 decades. Recognizing this, the WHO, in its newly released draft roadmap for NTD 2021–2030, has identified diagnostics as one of four priority areas requiring concerted action to reach the 2030 targets. As a result, WHO established a Diagnostics Technical Advisory Group (DTAG) to serve as the collaborative mechanism to drive progress in this area. Here, the purpose and role of the DTAG are described in the context of the challenges facing NTD programmes.

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“…Though not yet fully implemented in Africa, omics technologies and bioinformatics analyses have aided significantly in the generation of new knowledge toward drug and vaccine target discovery ( Yan et al, 2015 ; Xia, 2017 ). Genomic, transcriptomic and proteomic analyses of pathogens such as filariasis parasites have identified new potential biomarkers that can be invaluable in diagnostics, vaccine and drug development ( Armstrong et al, 2016 ; Bennuru et al, 2017 ). Kumar et al (2007) , using genome wide C. elegans RNA-interference data as proxy, identified a set of 3,059 essential genes in the B. malayi genome, from which 589 were characterized as potential drug targets.…”

Section: Application Of Omics To Vaccine Target Identification and Drmentioning

confidence: 99%

Highlights on the Application of Genomics and Bioinformatics in the Fight Against Infectious Diseases: Challenges and Opportunities in Africa

et al. 2018

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Genomics and bioinformatics are increasingly contributing to our understanding of infectious diseases caused by bacterial pathogens such as Mycobacterium tuberculosis and parasites such as Plasmodium falciparum. This ranges from investigations of disease outbreaks and pathogenesis, host and pathogen genomic variation, and host immune evasion mechanisms to identification of potential diagnostic markers and vaccine targets. High throughput genomics data generated from pathogens and animal models can be combined with host genomics and patients’ health records to give advice on treatment options as well as potential drug and vaccine interactions. However, despite accounting for the highest burden of infectious diseases, Africa has the lowest research output on infectious disease genomics. Here we review the contributions of genomics and bioinformatics to the management of infectious diseases of serious public health concern in Africa including tuberculosis (TB), dengue fever, malaria and filariasis. Furthermore, we discuss how genomics and bioinformatics can be applied to identify drug and vaccine targets. We conclude by identifying challenges to genomics research in Africa and highlighting how these can be overcome where possible.

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Mining Filarial Genomes for Diagnostic and Therapeutic Targets

Cited by 18 publications

References 125 publications

Long-read RNA sequencing of human and animal filarial parasites improves gene models and discovers operons

Long-read RNA sequencing of human and animal filarial parasites improves gene models and discovers operons

Diagnostics and the neglected tropical diseases roadmap: setting the agenda for 2030

Highlights on the Application of Genomics and Bioinformatics in the Fight Against Infectious Diseases: Challenges and Opportunities in Africa

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