Genetic and functional diversification of chemosensory pathway receptors in mosquito-borne filarial nematodes

Wheeler, Nicolas J; Heimark, Zachary W; Airs, Paul M; Mann, Alexis; Zamanian, Mostafa

doi:10.1101/683060

Cited by 3 publications

(11 citation statements)

References 124 publications

(133 reference statements)

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“…Bma-osm-9 CCS was captured, multiple CCSs from degraded transcripts validated the previously corrected splice recognition site in Bma-osm-9 (Fig. 6B) [60] . Finally, a read mapping to Bm17517 (an srt family chemoreceptor [60] ), showed evidence for a corrected or alternative TSS and start codon (Fig.…”

Section: Improvement Of Gene Models For Known and Putative Anthelmintsupporting

confidence: 69%

“…We report here the first long-read RNA-seq data for filarial nematodes, an important group of parasites that infect humans and animals. While the genome assembly of B. malayi is chromosome-scale, there remains serious errors in gene models, even for genes that are highly conserved among nematodes and have been cloned in other species [60] . D. immitis , on the other hand, has a far less contiguous genome assembly likely contains even more mispredicted gene models than B. malayi .…”

Section: Discussionmentioning

confidence: 99%

“…6B) [60] . Finally, a read mapping to Bm17517 (an srt family chemoreceptor [60] ), showed evidence for a corrected or alternative TSS and start codon (Fig. 6D).…”

Section: Improvement Of Gene Models For Known and Putative Anthelmintmentioning

confidence: 99%

“…More detailed sequencing statistics can be found in S1 Table. We assessed the quality of CCSs with SQANTI [30] , which reference-corrects, filters, and categorizes putative isoforms based on a number of quality control metrics, and we removed CCSs that had characteristics of reverse transcriptase template switching. After filtration, 60,230 and 71,267 CCSs remained from B. malayi and D. immitis , respectively ( Fig 1A). We identified CCSs mapping to 1,847/1,873 known genes in females, 1,651/1,433 in males, and 2,430/2,423 in both sexes ( Fig 1B), covering 54.2% and 44.6% of the B. malayi and D. immitis coding genomes, respectively.…”

Section: Sequencing Of the Four Libraries And Data Preparation With Imentioning

confidence: 99%

“…However, while the completeness of the B. malayi and D. immitis draft genomes is sufficient for target prioritization and selection via comparative genomic approaches, the fragmentation and incompleteness of predicted gene models can delay facile cloning, expression, and characterization or screening (see [10] , for instance). Despite the excellent chromosome-level assembly of the B. malayi genome [14] , two of three cloned genes in a recent study [15] had incorrectly predicted splice junctions even though these genes share high similarity with their one-to-one C. elegans homologs. Gene prediction and curation in Caenorhabditis spp.…”

Section: Introductionmentioning

confidence: 99%

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

Wheeler

Airs

Zamanian

2020

Preprint

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Filarial nematodes (Filarioidea) cause substantial disease burden to humans and animals around the world. Recently there has been a coordinated global effort to generate 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 10 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, identified 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 antiparasitic 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 future improvement of parasitic nematode genome assemblies. Author SummaryReference genomes for parasitic nematodes are important resources that enable the study of nematode evolution and molecular biology, and they also hold promise for hastening the development of chemotherapeutics to treat parasitic diseases. Recent years have seen an explosion in the availability of reference genomes for filarial worms, which cause diseases in both humans and animals, but much work remains to be done in order to fully potentiate the true utility of these resources. We carried out long-read RNA sequencing of Brugia malayi and Dirofilaria immitis , two important filarial worms that cause lymphatic filariasis and canine heartworm disease, respectively. We used these RNA sequencing data to correct many errors in the gene models of the reference genomes of these two species, and we also carried out novel analyses of poly(A) tails and operons. These datasets will greatly improve the B. malayi a...

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Section: Improvement Of Gene Models For Known and Putative Anthelmintsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

“…6B) [60] . Finally, a read mapping to Bm17517 (an srt family chemoreceptor [60] ), showed evidence for a corrected or alternative TSS and start codon (Fig. 6D).…”

Section: Improvement Of Gene Models For Known and Putative Anthelmintmentioning

confidence: 99%

Section: Sequencing Of the Four Libraries And Data Preparation With Imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wheeler

Airs

Zamanian

2020

Preprint

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Nematode nuclear receptors as integrators of sensory information

Sural

Hobert

2021

Current Biology

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Strongyloides RNA-seq Browser: a web-based software platform for on-demand bioinformatics analyses of Strongyloides species

Bryant¹,

DeMarco²,

Hallem³

2021

Preprint

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Soil-transmitted gastrointestinal parasitic nematodes infect approximately 1 billion people worldwide, predominantly in low-resource communities. Skin-penetrating gastrointestinal nematodes in the genus Strongyloides are emerging as model systems for mechanistic studies of soil-transmitted helminths due to the growing availability of functional genomics tools for these species. To facilitate future genomics studies of Strongyloides species, we have designed a web-based application, the Strongyloides RNA-seq Browser, that provides an open source, user-friendly portal for accessing and analyzing Strongyloides genomic expression data. Specifically, the Strongyloides RNA-seq Browser takes advantage of alignment-free read mapping tools and R-based transcriptomics tools to re-analyze publicly available RNA sequencing datasets from four Strongyloides species: Strongyloides stercoralis, Strongyloides ratti, Strongyloides papillosus, and Strongyloides venezuelensis. This application permits on-demand exploration and quantification of gene expression across life stages without requiring previous coding experience. Here, we describe this interactive application and demonstrate how it may be used by nematode researchers to conduct a standard set of bioinformatics queries.

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Genetic and functional diversification of chemosensory pathway receptors in mosquito-borne filarial nematodes

Cited by 3 publications

References 124 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

Nematode nuclear receptors as integrators of sensory information

Strongyloides RNA-seq Browser: a web-based software platform for on-demand bioinformatics analyses of Strongyloides species

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