Improving helminth genome resources in the post-genomic era

Trends in Parasitology, Год журнала: 2022, Номер 38(10), С. 831 - 840

Опубликована: Июль 6, 2022

Genomics resources for helminth parasites are growing rapidly; however, it is still difficult to fully assemble a genome so most vary significantly in completeness and contiguity.Genome annotations rely heavily on computational prediction shared orthology between closely (and sometimes not closely) related species, which can result incomplete incorrect may bias against some genes, such as those that species-specific or phylogenetically restricted.New approaches required generate, improve, extend these valuable resources.Community-based efforts could build exploit different areas of specific expertise, from single genes whole gene families, provide iterative improvement centralised resources.Coordinated annotation will new opportunities interaction collaboration among the parasitology community. Rapid advancement high-throughput sequencing analytical has seen steady increase generation genomic parasites. Now, genomes their cornerstone numerous compare genetic transcriptomic variation, cells populations globally distributed parasites, modifications understand function. Our understanding helminths increasingly reliant resources, primarily static once published widely quality species. This article seeks highlight cause effect this variation argues continued – even after publication necessary more accurate complete biology important pathogens. In 2022, first gapless human assembly was [1.Nurk S. et al.The sequence genome.Science. 2022; 376: 44-53Crossref PubMed Scopus (168) Google Scholar], little than 20 years landmark completion draft announced [2.International Human Genome Sequencing Consortium Finishing euchromatic genome.Nature. 2004; 431: 931-945Crossref (3472) Scholar]. publicly available resource multinational collaborative arguably one our scientific achievements. The impact project extends far beyond itself; technological made during Project driven ever-increasing accessibility 'genomics' study structure, composition, function, evolution other, nonhuman Such advances now allow genome-sequencing projects be undertaken all over world potentially any organism with accessible DNA, routine experiments found modest molecular laboratory extreme environments [3.Castro-Wallace S.L. al.Nanopore DNA International Space Station.Sci. Rep. 2017; 7: 18022Crossref (177) Scholar] response disease [4.Volz E. al.Assessing transmissibility SARS-CoV-2 lineage B.1.1.7 England.Nature. 2021; 593: 266-269Crossref (463) cataloguing life Earth [5.Lewin H.A. al.Earth BioGenome Project: future life.Proc. Natl. Acad. Sci. U. A. 2018; 115: 4325-4333Crossref (352) parasitic worms, collectively termed helminths, benefited revolution. Often considered 'neglected' affect billion people living lowest-resource countries worldwide global livestock agriculture industries. Despite neglect, several sustained have been generate broad aims including parasite life-history traits [6.International Helminth Genomes Comparative genomics major worms.Nat. Genet. 2019; 51: 163-174Crossref (216) mining drug targets [7.Cotton J.A. Onchocerca volvulus, agent river blindness.Nat. Microbiol. 2016; 2: 16216Crossref (62) characterising resistance [8.Doyle S.R. Cotton Genome-wide investigate anthelmintic resistance.Trends Parasitol. 35: 289-301Abstract Full Text PDF (37) principal repository data, WormBase ParaSite [9.Howe K.L. al.WormBase − comprehensive genomics.Mol. Biochem. 215: 2-10Crossref (277) contains 210 (see Glossary) 169 species nematodes flatworms (WormBase release 17), representing pathogenic humans, animals, plants well comparison. These starting point many form scaffold upon 'omic analyses rely. Although intentionally provocative somewhat oversimplified, there truth statement; its hypothesis structure content within an they derived but, despite best efforts, rarely resemble product. For example, biologically, defined cell assembled into discrete chromosomes often not, represented informatically by contigs scaffolds number thousands 'completeness' Figure 1 comparison assemblies BUSCO [10.Manni M. al.BUSCO Update: novel streamlined workflows along broader deeper phylogenetic coverage scoring eukaryotic, prokaryotic, viral genomes.Mol. Biol. Evol. 38: 4647-4654Crossref (283) 17; 80.9% 1000 contigs/scaffolds). recent advancements make cheaper, easier, likely produce highly contiguous chromosome-scale assemblies, challenging finished eukaryotic helminths. A key challenge molecular/sequencing/analytical approach optimised organisms. large particularly complex (the median size 122.18 Mb, range 38.18 Mb Meloidogyne graminicola 1.25 Gb Spirometra erinaceieuropaei), helminth-focused further challenged factors. challenges include: (i) vast differences morphology tissue both (i.e., stages) require extraction lead efficiencies [11.Ayana al.Comparison four three preservation protocols detection quantification soil-transmitted stool.PLoS Negl. Trop. Dis. 13e0007778Google Scholar,12.Doyle al.Evaluation methods individual egg larval stages whole-genome sequencing.Front. 10: 826Crossref (17) Scholar]; (ii) inaccessibility larger mature also vivo stages, whereas juvenile eggs larvae typically microscopic environmentally resistant, limiting yield [12]; (iii) based host geographic location, infecting worldwide, human-infective incredibly access low-resource settings where commonly [13.Doyle al.Population ancient modern Trichuris trichiura.bioRxiv. https://doi.org/10.1101/2021.10.21.464505Crossref (0) if available, preserve high-quality samples (tissue DNA) cold-chain limited; (iv) high degree heterogeneity individuals which, pooling sufficient sequencing, artefacts [14.Doyle al.Genomic defines Haemonchus contortus, model gastrointestinal worm.Commun. 2020; 3: 656Crossref (36) Some addressed overcome developments very low-input concentrations [15.Kingan S.B. al.a de novo mosquito using pacbio sequencing.Genes. 62Crossref (66) specimen sequenced. Nonetheless, issues undoubtedly limited ability each existing achieve reference genome. only part puzzle. Once 'finished', then determine coordinates coding, noncoding other feature genome, followed attempt identify characterise function annotations. Several pipelines developed annotating (for see description 50 Helminths pipeline, applied at scale). contrast, use combination tools Augustus [16.Hoff K.J. Stanke Predicting AUGUSTUS.Curr. Protoc. Bioinform. 65e57PubMed Braker [17.Brůna T. al.BRAKER2: automatic GeneMark-EP+ AUGUSTUS supported protein database.NAR Genom. 3lqaa108PubMed Maker [18.Holt C. Yandell MAKER2: pipeline genome-database management tool second-generation projects.BMC 2011; 12: 491Crossref (987) PASA [19.Haas B.J. al.Improving Arabidopsis maximal transcript alignment assemblies.Nucleic Acids Res. 2003; 31: 5654-5666Crossref (950) Scholar]) combine various additional datasets, RNA-seq data homologous sequences evidence putative features predictions dependent assembly, type amount used, how representative mapped broadly good intron–exon splice junctions models; towards expressed, lowly expressed stage/condition were predicted reliably. While perform well, given evidence, under ideal scenario errors [20.Salzberg Next-generation annotation: we struggle get right.Genome 20: 92Crossref (105) Many evident until manually inspected, gene-by-gene, browser; coding 16 380 (ranging 8140 flexuosa 101 269 arenaria), trivial task. Unfortunately, generated scenario, fewer thoroughly interrogated manually. Examples include models fragmented multiple incorrectly merged, broken technical stop codons frameshifts, missing due lack divergence training dataset. complicate used define evolutionary functional relationships confounds estimates [21.Weisman C.M. al.Mixing comparative analysis inflates apparent lineage-specific genes.Curr. 32: 1-8Abstract (3) examples literature describe cloning validation identifying error resource; unfortunately, updated experimentally validated correct original resource. Further associated characterisation non-model organisms It recently estimated 47% families rendering 'hypothetical' [22.International Molecular Helminthology Annotation Network (IMHAN) al.Tackling hypotheticals genomes.Trends 34: 179-183Abstract do information relied computation inference homology information, thereof, interpreting difficult; region interest reveal list no known set enrichment biased functions common ontologies. Because immediately obvious, scale, research repeatedly and, consequently, benefit identified. Furthermore, limitations known, effort update therefore, impractical, especially genome-wide annotation. More necessarily solution, direct novel, parasite-specific roles needed [23.Viney failure biology.Trends 2014; 30: 319-321Abstract (12) deciphering role hypothetical proteins, enhanced 3D AlphaFold [24.Jumper J. al.Highly AlphaFold.Nature. 596: 583-589Crossref (4221) However, without improvements coordination feedback based, progress better ultimately limited. 'post-genomic' era, rate scale steadily [25.McVeigh P. Post-genomic parasitology.Parasitology. 147: 835-840Crossref (13) Genome-led include, transcription single-cell [26.Diaz Soria C.L. al.Single-cell atlas intra-mammalian developmental stage Schistosoma mansoni.Nat. Commun. 11: 6411Crossref (22) Scholar, 27.Wendt G. al.A mansoni identifies regulator blood feeding.Science. 369: 1644-1649Crossref (48) 28.Li conserved program controlling germline stem fate.Nat. 485Crossref (14) temporal [29.Rawlinson K.A. al.Daily rhythms expression mansoni.BMC 19: 255Crossref (5) spatially resolutions [30.Airs P.M. al.Spatial transcriptomics reveals antiparasitic essential behaviors Brugia malayi.PLoS Pathog. 18e1010399Crossref (2) large-scale RNAi screens [31.Wang al.Large-scale screening uncovers therapeutic mansoni.Science. 1649-1653Crossref (28) extensive family characterisation, chemoreceptors [32.Wheeler N.J. al.Genetic diversification chemosensory pathway receptors mosquito-borne filarial nematodes.PLoS 18e3000723Crossref small RNAs [33.Fontenla al.Lost found: Piwi Argonaute pathways flatworms.Front. Cell. Infect. 11653695Crossref (4) targeted modification transgenesis becoming efficient [34.Gang S.S. al.Targeted mutagenesis human-parasitic nematode.PLoS 13e1006675Crossref (69) 35.Ittiprasert W. al.Programmed editing omega-1 ribonuclease fluke, mansoni.eLife. 8e41337Crossref 36.Arunsan knockout mutation liver fluke granulin attenuates virulence infection-induced hepatobiliary morbidity.eLife. 8e41463Crossref (40) 37.Sankaranarayanan al.Large CRISPR-Cas-induced deletions oxamniquine locus parasite.Wellcome Open 5: 178Crossref (11) being complemented proteomics [38.Wang al.Somatic proteome contortus.Int. 49: 311-320Crossref (27) peptidomics [39.Buzy al.Peptidomics contortus.ACS Omega. 6: 10288-10305Crossref metabolomics [40.Kokova D. Mayboroda O.A. Twenty on: research.Trends 282-288Abstract lipidomics [41.Wang al.Helminth lipidomics: aspects prospects.Curr. Vector Borne 1100018Google generating 'omics problematic. problem assumption essentially 'correct' previous subheading); erroneous, biological insights surely missed or, worse, misinterpreted. second information-rich datasets significant potential add value but rarely, ever, so. largely that, published, change; whether primary synthesis remain distinct improve enrich based. Addressing two points focus time reference-quality (Figure 2). led fundamental resolution QTL contortus [42.Doyle modelling ivermectin nematode, contortus.BMC 218Crossref Scholar,43.Doyle landscape mediators resistance.bioRxiv. https://doi.org/10.1101/2021.11.12.465712Crossref sex malayi species) [44.Foster J.M. al.Sex chromosome humans.Nat. 1964Crossref delineation separate Z W [45.Buddenborg S.K. al.Assembled insight ZW sex-determination system.bioRxiv. https://doi.org/10.1101/2021.08.13.456314Crossref unusual centromere telomere structures ends Hymenolepis microstoma [46.Olson P.D. al.Complete representation tapeworm capped centromeres, necessitating dual segregation protection.BMC 18: 165Crossref demonstrate achieved measurable effects made. Therefore, question remains: (or should) done broadly, whom? (Box outlines access, synthesis, extension helminths). improvement, (as described above 2), groups working motivated question. currently, B. malayi, Strongyloides ratti, muris dedicated manual curation ongoing core group (which includes Caenorhabditis elegans, spp., Pristionchus pacificus), 2 describes H. annotation). remaining 95% ParaSite, scope seems less certain, relying curators unlikely diversity required. communities greater cumulative expertise; although contribute knowledge via resource, remains itself. opportunity needs taken advantage of. What currently lacking mechanisms easily transferred integrated dynamic change time. mechanism should scales, curating single-gene describing more. mechanism, when final product, seem therefore unachievable, already easy-to-use (e.g., Web Apollo [47.Dunn N.A. al.Apollo: democratizing annotation.PLoS Comput. 15e1006790Crossref (99) initiatives underway experts non-experts alike goal improving nematode Box trichiura pacificus annotations). platform integrate synthesise providing improved open restriction.Box 1Access, helminths1.Depositing open-access repositories•NCBIi: DNA/protein sequences, focussed genomes.•ENAii & SRAiii: raw reads, genomes, annotations.•WormBase ParaSiteiv: free-living platyhelminths.2.Synthesis resources•WormBase ParaSiteivoAlthough annotations, inferred UniProtv, specieso(Re-)integrates genomes/annotations become available. 17 species.oRuns Ensembl Compara sets refining genesets added.•AlphaFold Scholar]vi select worm proteomes, including: Dracunculus medinensis, mansoni, stercoralis, trichiura, Wuchereria bancrofti•Tools: gVAL [48.Howe K. al.Significantly through curation.GigaScience. 10giaa153Crossref G-OnRamp [49.Sargent L. al.G-OnRamp: Generating browsers facilitate undergraduate-driven 16e1007863Crossref Scholar].3.Development resources•Dedicated WormBasevii.oCurrently, six species.oCuration semi-automated, machine-learning components variants complement curation, reviewed [50.Davis 2022-data, processes, analyzing elegans.Genetics. 220iyac003Crossref Scholar].•Introduction technologies contiguity [e.g., conformation capture (HiC), optical mapping] long-read RNAseq, proteomics).oExamples: japonicum [51.Luo F. al.An japonicum.PLoS 13e0007612Crossref (29) haematobium [52.Stroehlein A.J. al.Chromosome-level underpins explorations variation.PLoS 18e1010288Crossref Sc

Язык: Английский

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Genomic evidence of contemporary hybridization between Schistosoma species

PLoS Pathogens, Год журнала: 2022, Номер 18(8), С. e1010706 - e1010706

Опубликована: Авг. 8, 2022

Hybridization between different species of parasites is increasingly being recognised as a major public and veterinary health concern at the interface infectious diseases biology, evolution, epidemiology ultimately control. Recent research has revealed that viable hybrids introgressed lineages Schistosoma spp. are prevalent across Africa beyond, including those with zoonotic potential. However, it remains unclear whether these hybrid represent recent hybridization events, suggesting ongoing, and/or they derived from ancient events. In human schistosomiasis, investigation hampered by inaccessibility adult-stage worms due to their intravascular location, an issue which can be circumvented post-mortem livestock abattoirs for known To characterise composition naturally-occurring schistosome hybrids, we performed whole-genome sequencing 21 natural infective isolates. facilitate this, also assembled de novo chromosomal-scale draft assembly curassoni . Genomic analyses identified isolates S bovis , two species, all were early generation multiple generations found within same host. These results show ongoing process populations potential further challenge elimination efforts against schistosomiasis.

Язык: Английский

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A single locus determines praziquantel response in Schistosoma mansoni

Antimicrobial Agents and Chemotherapy, Год журнала: 2024, Номер 68(3)

Опубликована: Янв. 30, 2024

We previously performed a genome-wide association study (GWAS) to identify the genetic basis of praziquantel (PZQ) response in schistosomes, identifying two quantitative trait loci situated on chromosomes 2 and 3. reanalyzed this GWAS using latest (version 10) genome assembly showing that single locus chromosome 3, rather than independent loci, determines drug response. These results reveal PZQ is monogenic demonstrates importance high-quality genomic information.

Язык: Английский

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Schistosomiasis diagnosis: Challenges and opportunities for elimination

PLoS neglected tropical diseases, Год журнала: 2024, Номер 18(7), С. e0012282 - e0012282

Опубликована: Июль 11, 2024

Overview The roadmap adopted by the World Health Organization (WHO) for eliminating neglected tropical diseases aims to eliminate schistosomiasis, as a public health concern, 2030. While progress has been made towards reducing schistosomiasis morbidity control in several sub-Saharan African countries, there is still more that needs be done. Proper surveillance using accurate diagnostics with acceptable sensitivity and specificity essential evaluating success of all efforts against schistosomiasis. Microscopy, despite its low sensitivity, remains gold standard approach diagnosing disease. Although many have develop new based on circulating parasite proteins, genetic markers, schistosome egg morphology, their paramagnetic properties, none robust enough replace microscopy. This review highlights common diagnostic approaches detecting field clinical settings, major challenges, provides novel opportunities diagnosis pathways will critical supporting elimination Methods We searched relevant reliable published literature from PubMed, Scopus, google scholar, Web science. search strategies were primarily determined subtopic, hence following words used (schistosom*, diagnosis, Kato–Katz, antibody test, antigen, POC-CCA, UCP-LF-CAA, molecular diagnostics, nucleic acid amplification microfluidics, lab-on disk, chip, recombinase polymerase (RPA), LAMP, portable sequencer, nanobody identical multi-repeat sequences, TPPs, REASSURED, extraction free), Boolean operators AND and/OR refine searching capacity. Due global nature we also documents, reports, research papers international organizations, (WHO), Center Disease Elimination.

Язык: Английский

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Schistosoma haematobium and Schistosoma bovis first generation hybrids undergo gene expressions changes consistent with species compatibility and heterosis

PLoS neglected tropical diseases, Год журнала: 2024, Номер 18(7), С. e0012267 - e0012267

Опубликована: Июль 2, 2024

When two species hybridize, the parental genomes are brought together and some alleles might interact for first time. To date, extent of transcriptomic changes in hybrid generations, along with their functional outcome constitute an important knowledge gap, especially parasite species. Here we explored molecular outcomes hybridization first-generation hybrids between blood fluke parasites Schistosoma haematobium S. bovis. Through a approach, measured gene expression both hybrids. We described quantified profiles encountered main biological processes impacted. Up to 7,100 genes fell into particular profile (intermediate levels, over-expressed, under-expressed, or expressed like one lines). Most these were different depending on direction cross (S. bovis mother father reverse) sex. For given sex direction, vast majority hence unassigned profile: either they differentially but not typical any neither lines nor lines. The most prevalent was intermediate (24% investigated genes). These results suggest that compatibility remains quite high. also found support over-dominance model (over- under-expressed compared lines) potentially associated heterosis. In females particular, such as reproductive processes, metabolism cell interactions well signaling pathways indeed affected. Our study provides new insight biology evidences supporting

Язык: Английский

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Human Alveolar Echinococcosis—A Neglected Zoonotic Disease Requiring Urgent Attention

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2784 - 2784

Опубликована: Март 19, 2025

Alveolar echinococcosis (AE) in humans is caused by the larval (metacestode) stage of Echinococcus multilocularis, commonly known as ‘fox tapeworm’. This disease predominantly targets liver and has an invasive growth pattern, allowing it to spread adjacent distant tissues. Due its gradual progression tumour-like characteristics, early diagnosis prompt intervention are crucial, particularly there currently no highly effective vaccines or chemotherapeutics against AE. Current estimates suggest that ~10,500 new infections occur annually worldwide; however, more research required refine prevalence incidence data for both human animal hosts endemic areas world. article discusses biology E. outlines aspects pathogenesis, diagnosis, treatment, management AE, reviews global distribution, annual incidence, prevalence, highlights role molecular parasitology advancing therapeutic strategies, presents recommendations improving prevention control AE populations.

Язык: Английский

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Genomic data reveal a north-south split and introgression history of blood fluke populations across Africa

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 13, 2025

Язык: Английский

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The research contribution of the Schistosomiasis Collection at the Natural History Museum (SCAN): highlights, challenges and future directions

Infectious Diseases of Poverty, Год журнала: 2025, Номер 14(1)

Опубликована: Апрель 18, 2025

Abstract Background The Schistosomiasis Collection at the Natural History Museum (SCAN) is a repository of schistosomiasis-related specimens, development which was funded by Wellcome Trust between 2011 and 2021. With view to facilitating research improving access genetically diverse material, SCAN built from legacy collections specimens amassed over decades, with more recent made through partnership large field-based projects. Methods We identified literature associated 2012 until 2024, using both database searches (search terms: SCAN, schistosomiasis collection NHM schistosomiasis) citations publication originally laid out scope Collection. Studies were included if cited, and/or utilised in work. Data extracted year publication, authors, whether how used work, type used. Results includes 88 published works, demonstrating utility supporting research. comprises around half million larval schistosomes originating field, approximately 3000 specimen lots lab-passaged adult parasites stored liquid nitrogen. 11 schistosome species, majority being human pathogens Schistosoma haematobium S. mansoni , while also including many livestock-associated species. Genome analysis S . guineensis samples indicate historical introgression or ongoing hybridisation. In order representation, (> 19,000 forms eggs, 550 laboratory passaged worms), japonicum bovis curassoni mattheei rodhaini intercalatum margrebowiei spindale represented only laboratory-passaged isolates 210,000 snails, as whole encompassing 27 countries. Conclusions Improvements DNA sequencing techniques have allowed genome-level data be accessed archived retrospective collected decades ago. has been use exploring diversity, particularly reference hybridisation drug resistance. Multiple author nationalities demonstrate collaborative nature Collection, although may need done future, promote work led developing countries ensure effective collaboration sample sharing. Graphical

Язык: Английский

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Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution

Parasites & Vectors, Год журнала: 2024, Номер 17(1)

Опубликована: Май 8, 2024

Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum endemic to Asia; Z chromosome S. comprises one-quarter entire genome. Detection positive selection using resequencing data understand adaptive evolution has been applied variety pathogens, including japonicum. However, contribution and adaptation often neglected. We obtained 1,077,526 high-quality SNPs on in 72 re-sequencing publicly. To examine faster effect, we compared sequence divergence two closely related species, haematobium mansoni. Genetic diversity was between autosomes calculating nucleotide (π) Dxy values. Population structure also assessed based PCA analysis. Besides, employed multiple methods Tajima's D, FST, iHS, XP-EHH, CMS detect signals chromosome. Further RNAi knockdown experiments were performed investigate potential biological functions candidate genes. Our study found showed more pronounced genetic than autosomes, although effect may be smaller variation among Compared had sub-populations. Notably, identified set genes associated host-parasite co-evolution. In particular, LCAT exhibited significant within Taiwan population. RNA interference suggested necessary for survival propagation definitive host. addition, several specificity intermediate host C-M population, Rab6 VCP, which are involved immune evasion provides valuable insights into further advances our understanding co-evolution this medically important parasite its hosts.

Язык: Английский

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Genome-wide RNA interference of the nhr gene family in barber's pole worm identified members crucial for larval viability in vitro

Infection Genetics and Evolution, Год журнала: 2024, Номер 122, С. 105609 - 105609

Опубликована: Май 26, 2024

Nuclear hormone receptors (NHRs) are emerging target candidates against nematode infection and resistance. However, there is a lack of comprehensive information on NHR-coding genes in parasitic nematodes. In this study, we curated the nhr gene family for 60 major nematodes from humans animals. Compared with free-living model organism Caenorhabditis elegans, remarkable contraction was revealed species, genetic diversification conservation unveiled among Clades I (10-13), III (16-42), IV (33-35) V (25-64). Using an vitro biosystem, demonstrated that 40 blood-feeding Haemonchus contortus (clade V; barber's pole worm) were responsive to host serum one (i.e., nhr-64) consistently stimulated by anthelmintics ivermectin, thiabendazole levamisole); high-throughput RNA interference platform, knocked down 43 H. identified at least two required viability nhr-105) development nhr-17) infective larvae vitro. Harnessing preliminary functional atlas will prime biological studies genetics, infection, anthelmintic metabolism within animals, as well promising discovery novel intervention targets.

Язык: Английский

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