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OGEE is an Online GEne Essentiality database. Gene essentiality is not a static and binary property, rather a context-dependent and evolvable property in all forms of life. In OGEE we collect not only experimentally tested essential and non-essential genes, but also associated gene properties that contributes to gene essentiality. We tagged conditionally essential genes that show variable essentiality statuses across datasets to highlight complex interplays between gene functions and environmental/experimental perturbations. OGEE v3 contains gene essentiality datasets for 91 species; almost doubled from 48 species in previous version. To accommodate recent advances on human cancer essential genes (as known as tumor dependency genes) that could serve as targets for cancer treatment and/or drug development, we expanded the collection of human essential genes from 16 cell lines in previous to 581. These human cancer cell lines were tested with high-throughput experiments such as CRISPR-Cas9 and RNAi; in total, 150 of which were tested by both techniques. We also included factors known to contribute to gene essentiality for these cell lines, such as genomic mutation, methylation and gene expression, along with extensive graphical visualizations for ease of understanding of these factors. OGEE v3 can be accessible freely at https://v3.ogee.info., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Advances in nucleic acid sequencing, mass spectrometry and computational biology have facilitated the identification, annotation and analysis of genes, transcripts, proteins and metabolites in model nematodes (Caenorhabditis elegans and Pristionchus pacificus) and socioeconomically important parasitic nematodes (Clades I, III, IV and V). Significant progress has been made in genomics and transcriptomics as well as in the proteomics and lipidomics of Haemonchus contortus (the barber's pole worm) - one of the most pathogenic representatives of the order Strongylida. Here, we review salient aspects of genomics, transcriptomics, proteomics, lipidomics, glycomics and functional genomics, and discuss the rise of integrative 'omics of this economically important parasite. Although our knowledge of the molecular biology, genetics and biochemistry of H. contortus and related species has progressed significantly, much remains to be explored, particularly in areas such as drug resistance, unique/unknown genes, host-parasite interactions, parasitism and the pathogenesis of disease, by integrating the use of multiple 'omics methods. This approach should lead to a better understanding of H. contortus and its relatives at a 'systems biology' level, and should assist in developing new interventions against these parasites., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Here, we created an automated pipeline for the de novoassembly of genomes from Pacific Biosciences long-read and Illumina short-read data using common workflow language (CWL). To evaluate the performance of this pipeline, we assembled the nuclear genomes of the eukaryotes Caenorhabditis elegans (∼100 Mb), Drosophila melanogaster (∼138 Mb), and Plasmodium falciparum (∼23 Mb) directly from publicly accessible nucleotide sequence datasets and assessed the quality of the assemblies against curated reference genomes., Findings: We showed a dependency of the accuracy of assembly on sequencing technology and GC content and repeatedly achieved assemblies that meet the high standards set by the National Human Genome Research Institute, being applicable to gene prediction and subsequent genomic analyses., Conclusions: This CWL pipeline overcomes current challenges of achieving repeatability and reproducibility of assembly results and offers a platform for the re-use of the workflow and the integration of diverse datasets. This workflow is publicly available via GitHub (https://github.com/vetscience/Assemblosis) and is currently applicable to the assembly of haploid and diploid genomes of eukaryotes., (© The Author(s) 2019. Published by Oxford University Press.)

Clonorchis sinensis (family Opisthorchiidae) is an important foodborne parasite that has a major socioeconomic impact on ~35 million people predominantly in China, Vietnam, Korea and the Russian Far East. In humans, infection with C. sinensis causes clonorchiasis, a complex hepatobiliary disease that can induce cholangiocarcinoma (CCA), a malignant cancer of the bile ducts. Central to understanding the epidemiology of this disease is knowledge of genetic variation within and among populations of this parasite. Although most published molecular studies seem to suggest that C. sinensis represents a single species, evidence of karyotypic variation within C. sinensis and cryptic species within a related opisthorchiid fluke (Opisthorchis viverrini) emphasise the importance of studying and comparing the genes and genomes of geographically distinct isolates of C. sinensis. Recently, we sequenced, assembled and characterised a draft nuclear genome of a C. sinensis isolate from Korea and compared it with a published draft genome of a Chinese isolate of this species using a bioinformatic workflow established for comparing draft genome assemblies and their gene annotations. We identified that 50.6% and 51.3% of the Korean and Chinese C. sinensis genomic scaffolds were syntenic, respectively. Within aligned syntenic blocks, the genomes had a high level of nucleotide identity (99.1%) and encoded 15 variable proteins likely to be involved in diverse biological processes. Here, we review current technical challenges of using draft genome assemblies to undertake comparative genomic analyses to quantify genetic variation between isolates of the same species. Using a workflow that overcomes these challenges, we report on a high-quality draft genome for C. sinensis from Korea and comparative genomic analyses, as a basis for future investigations of the genetic structures of C. sinensis populations, and discuss the biotechnological implications of these explorations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Trichinellosis is a globally important food-borne parasitic disease of humans caused by roundworms of the Trichinella complex. Extensive biological diversity is reflected in substantial ecological and genetic variability within and among Trichinella taxa, and major controversy surrounds the systematics of this complex. Here we report the sequencing and assembly of 16 draft genomes representing all 12 recognized Trichinella species and genotypes, define protein-coding gene sets and assess genetic differences among these taxa. Using thousands of shared single-copy orthologous gene sequences, we fully reconstruct, for the first time, a phylogeny and biogeography for the Trichinella complex, and show that encapsulated and non-encapsulated Trichinella taxa diverged from their most recent common ancestor ∼21 million years ago (mya), with taxon diversifications commencing ∼10-7 mya.

Background: Schistosomiasis is a parasitic disease affecting ~200 million people worldwide. Schistosoma haematobium and S. mansoni are two relatively closely related schistosomes (blood flukes), and the causative agents of urogenital and hepatointestinal schistosomiasis, respectively. The availability of genomic, transcriptomic and proteomic data sets for these two schistosomes now provides unprecedented opportunities to explore their biology, host interactions and schistosomiasis at the molecular level. A particularly important group of molecules involved in a range of biological and developmental processes in schistosomes and other parasites are the G protein-coupled receptors (GPCRs). Although GPCRs have been studied in schistosomes, there has been no detailed comparison of these receptors between closely related species. Here, using a genomic-bioinformatic approach, we identified and characterised key GPCRs in S. haematobium and S. mansoni (two closely related species of schistosome)., Methods: Using a Hidden Markov Model (HMM) and Support Vector Machine (SVM)-based pipeline, we classified and sub-classified GPCRs of S. haematobium and S. mansoni, combined with phylogenetic and transcription analyses., Results: We identified and classified classes A, B, C and F as well as an unclassified group of GPCRs encoded in the genomes of S. haematobium and S. mansoni. In addition, we characterised ligand-specific subclasses (i.e. amine, peptide, opsin and orphan) within class A (rhodopsin-like)., Conclusions: Most GPCRs shared a high degree of similarity and conservation, except for members of a particular clade (designated SmGPR), which appear to have diverged between S. haematobium and S. mansoni and might explain, to some extent, some of the underlying biological differences between these two schistosomes. The present set of annotated GPCRs provides a basis for future functional genomic studies of cellular GPCR-mediated signal transduction and a resource for future drug discovery efforts in schistosomes.

BackgroundArthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods.ResultsUsing 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception.ConclusionsThese analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.

Genomic data provide valuable insights into pest management issues such as resistance evolution, historical patterns of pest invasions and ongoing population dynamics. We assembled the first reference genome for the redlegged earth mite, Halotydeus destructor (Tucker, 1925), to investigate adaptation to pesticide pressures and demography in its invasive Australian range using whole‐genome pool‐seq data from regionally distributed populations. Our reference genome comprises 132 autosomal contigs, with a total length of 48.90 Mb. We observed a large complex of ace genes, which has presumably evolved from a long history of organophosphate selection in H. destructor and may contribute towards organophosphate resistance through copy number variation, target‐site mutations and structural variants. In the putative ancestral H. destructor ace gene, we identified three target‐site mutations (G119S, A201S and F331Y) segregating in organophosphate‐resistant populations. Additionally, we identified two new para sodium channel gene mutations (L925I and F1020Y) that may contribute to pyrethroid resistance. Regional structuring observed in population genomic analyses indicates that gene flow in H. destructor does not homogenize populations across large geographic distances. However, our demographic analyses were equivocal on the magnitude of gene flow; the short invasion history of H. destructor makes it difficult to distinguish scenarios of complete isolation vs. ongoing migration. Nonetheless, we identified clear signatures of reduced genetic diversity and smaller inferred effective population sizes in eastern vs. western populations, which is consistent with the stepping‐stone invasion pathway of this pest in Australia. These new insights will inform development of diagnostic genetic markers of resistance, further investigation into the multifaceted organophosphate resistance mechanism and predictive modelling of resistance evolution and spread. [ABSTRACT FROM AUTHOR]

Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting > 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital tissues, and can lead to increased susceptibility to HIV/AIDS and squamous cell carcinoma of the bladder. To complement available treatment programs and break the transmission of disease, sound knowledge and understanding of the biology and ecology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease and the effectiveness of control programs including mass drug administration. Here we report the first chromosome-contiguous genome for a well-defined laboratory line of this blood fluke. An exploration of this genome using transcriptomic data for all key developmental stages allowed us to refine gene models (including non-coding elements) and annotations, discover 'new' genes and transcription profiles for these stages, likely linked to development and/or pathogenesis. Molecular variation within S. haematobium among some geographical locations in Africa revealed unique genomic 'signatures' that matched species other than S. haematobium, indicating the occurrence of introgression events. The present reference genome (designated Shae.V3) and the findings from this study solidly underpin future functional genomic and molecular investigations of S. haematobium and accelerate systematic, large-scale population genomics investigations, with a focus on improved and sustained control of urogenital schistosomiasis. Author summary: More than 100 million people are infected with the carcinogenic blood fluke Schistosoma haematobium, the aetiological agent of urogenital schistosomiasis—a neglected tropical disease (NTD). In spite of its major significance, little is known about this fluke, its interactions with the human and snail intermediate hosts and the pathogenesis of the urogenital form of schistosomiasis at the molecular and biochemical levels. To enable research in these areas, we report the first chromosome-level genome and markedly enhanced gene models for S. haematobium. Comparative genomic analyses also reveal evidence of past introgression events between or among closely related schistosome species. This present reference genome for S. haematobium and the findings from this study should underpin future functional genomic and molecular investigations of S. haematobium and accelerate systematic, large-scale population genomics investigations, with a focus on improved control of urogenital schistosomiasis. [ABSTRACT FROM AUTHOR]

Colletotrichum tanaceti is an emerging foliar fungal pathogen of commercially grown pyrethrum (Tanacetum cinerariifolium). Despite being reported consistently from field surveys in Australia, the molecular basis of pathogenicity of C. tanaceti on pyrethrum is unknown. Herein, the genome of C. tanaceti (isolate BRIP57314) was assembled de novo and annotated using transcriptomic evidence. The inferred putative pathogenicity gene suite of C. tanaceti comprised a large array of genes encoding secreted effectors, proteases, CAZymes and secondary metabolites. Comparative analysis of its putative pathogenicity gene profiles with those of closely related species suggested that C. tanaceti likely has additional hosts to pyrethrum. The genome of C. tanaceti had a high repeat content and repetitive elements were located significantly closer to genes inferred to influence pathogenicity than other genes. These repeats are likely to have accelerated mutational and transposition rates in the genome, resulting in a rapid evolution of certain CAZyme families in this species. The C. tanaceti genome showed strong signals of Repeat Induced Point (RIP) mutation which likely caused its bipartite nature consisting of distinct gene-sparse, repeat and A-T rich regions. Pathogenicity genes within these RIP affected regions were likely to have a higher evolutionary rate than the rest of the genome. This “two-speed” genome phenomenon in certain Colletotrichum spp. was hypothesized to have caused the clustering of species based on the pathogenicity genes, to deviate from taxonomic relationships. The large repertoire of pathogenicity factors that potentially evolve rapidly due to the plasticity of the genome, indicated that C. tanaceti has a high evolutionary potential. Therefore, C. tanaceti poses a high-risk to the pyrethrum industry. Knowledge of the evolution and diversity of the putative pathogenicity genes will facilitate future research in disease management of C. tanaceti and other Colletotrichum spp. [ABSTRACT FROM AUTHOR]

Intestinal infection by the parasitic blood fluke Schistosoma bovis is a common veterinary problem in Africa and the Middle East and occasionally in the Mediterranean Region. The species also has the ability to form interspecific hybrids with the human parasite S. haematobium with natural hybridisation observed in West Africa, presenting possible zoonotic transmission. Additionally, this exchange of alleles between species may dramatically influence disease dynamics and parasite evolution. We have generated a 374 Mb assembly of the S. bovis genome using Illumina and PacBio-based technologies. Despite infecting different hosts and organs, the genome sequences of S. bovis and S. haematobium appeared strikingly similar with 97% sequence identity. The two species share 98% of protein-coding genes, with an average sequence identity of 97.3% at the amino acid level. Genome comparison identified large continuous parts of the genome (up to several 100 kb) showing almost 100% sequence identity between S. bovis and S. haematobium. It is unlikely that this is a result of genome conservation and provides further evidence of natural interspecific hybridization between S. bovis and S. haematobium. Our results suggest that foreign DNA obtained by interspecific hybridization was maintained in the population through multiple meiosis cycles and that hybrids were sexually reproductive, producing viable offspring. The S. bovis genome assembly forms a highly valuable resource for studying schistosome evolution and exploring genetic regions that are associated with species-specific phenotypic traits. [ABSTRACT FROM AUTHOR]

Background: Blood flukes of the genus Schistosoma cause schistosomiasis—a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium—the causative agent of urogenital schistosomiasis of humans. Methodology: MicroRNAs (miRNAs) and other sncRNAs of male and female adults of S. haematobium and small RNA transcription levels were explored by deep sequencing, genome mapping and detailed bioinformatic analyses. Principal findings: In total, 89 transcribed miRNAs were identified in S. haematobium—a similar complement to those reported for the congeners S. mansoni and S. japonicum. Of these miRNAs, 34 were novel, with no homologs in other schistosomes. Most miRNAs (n = 64) exhibited sex-biased transcription, suggestive of roles in sexual differentiation, pairing of adult worms and reproductive processes. Of the sncRNAs that were not miRNAs, some related to the spliceosome (n = 21), biogenesis of other RNAs (n = 3) or ribozyme functions (n = 16), whereas most others (n = 3798) were novel (‘orphans’) with unknown functions. Conclusions: This study provides the first genome-wide sncRNA resource for S. haematobium, extending earlier studies of schistosomes. The present work should facilitate the future curation and experimental validation of sncRNA functions in schistosomes to enhance our understanding of post-transcriptional gene regulation and of the roles that sncRNAs play in schistosome reproduction, development and parasite-host cross-talk. [ABSTRACT FROM AUTHOR]

The availability of high-quality genomes and advances in functional genomics have enabled large-scale studies of essential genes in model eukaryotes, including the 'elegant worm' (Caenorhabditis elegans ; Nematoda) and the 'vinegar fly' (Drosophila melanogaster ; Arthropoda). However, this is not the case for other, much less-studied organisms, such as socioeconomically important parasites, for which functional genomic platforms usually do not exist. Thus, there is a need to develop innovative techniques or approaches for the prediction, identification and investigation of essential genes. A key approach that could enable the prediction of such genes is machine learning (ML). Here, we undertake an historical review of experimental and computational approaches employed for the characterisation of essential genes in eukaryotes, with a particular focus on model ecdysozoans (C. elegans and D. melanogaster), and discuss the possible applicability of ML-approaches to organisms such as socioeconomically important parasites. We highlight some recent results showing that high-performance ML, combined with feature engineering, allows a reliable prediction of essential genes from extensive, publicly available 'omic data sets, with major potential to prioritise such genes (with statistical confidence) for subsequent functional genomic validation. These findings could 'open the door' to fundamental and applied research areas. Evidence of some commonality in the essential gene-complement between these two organisms indicates that an ML-engineering approach could find broader applicability to ecdysozoans such as parasitic nematodes or arthropods, provided that suitably large and informative data sets become/are available for proper feature engineering, and for the robust training and validation of algorithms. This area warrants detailed exploration to, for example, facilitate the identification and characterisation of essential molecules as novel targets for drugs and vaccines against parasitic diseases. This focus is particularly important, given the substantial impact that such diseases have worldwide, and the current challenges associated with their prevention and control and with drug resistance in parasite populations. [ABSTRACT FROM AUTHOR]

Abstract: Compounded by a massive global food shortage, many parasitic diseases have a devastating, long-term impact on animal and human health and welfare worldwide. Parasitic helminths (worms) affect the health of billions of animals. Unlocking the systems biology of these neglected pathogens will underpin the design of new and improved interventions against them. Currently, the functional annotation of genomic and transcriptomic sequence data for socio-economically important parasitic worms relies almost exclusively on comparative bioinformatic analyses using model organism- and other databases. However, many genes and gene products of parasitic helminths (often >50%) cannot be annotated using this approach, because they are specific to parasites and/or do not have identifiable homologs in other organisms for which sequence data are available. This inability to fully annotate transcriptomes and predicted proteomes is a major challenge and constrains our understanding of the biology of parasites, interactions with their hosts and of parasitism and the pathogenesis of disease on a molecular level. In the present article, we compiled transcriptomic data sets of key, socioeconomically important parasitic helminths, and constructed and validated a curated database, called HelmDB (www.helmdb.org). We demonstrate how this database can be used effectively for the improvement of functional annotation by employing data integration and clustering. Importantly, HelmDB provides a practical and user-friendly toolkit for sequence browsing and comparative analyses among divergent helminth groups (including nematodes and trematodes), and should be readily adaptable and applicable to a wide range of other organisms. This web-based, integrative database should assist ‘systems biology’ studies of parasitic helminths, and the discovery and prioritization of novel drug and vaccine targets. This focus provides a pathway toward developing new and improved approaches for the treatment and control of parasitic diseases, with the potential for important biotechnological outcomes. [Copyright &y& Elsevier]

Flystrike, or cutaneous myiasis, is caused by blow fly larvae of the genus Lucilia. This disease is a major problem in countries with large sheep populations. In Australia, Lucilia cuprina (Wiedemann, 1830) is the principal fly involved in flystrike. While much research has been conducted on L. cuprina, including physical, chemical, immunological, genetic and biological investigations, the molecular biology of this fly is still poorly understood. The recent sequencing, assembly and annotation of the draft genome and analyses of selected transcriptomes of L. cuprina have given a first global glimpse of its molecular biology and insights into host-fly interactions, insecticide resistance genes and intervention targets. The present article introduces L. cuprina, flystrike and associated issues, details past control efforts and research foci, reviews salient aspects of the L. cuprina genome project and discusses how the new genomic and transcriptomic resources for this fly might accelerate fundamental molecular research of L. cuprina towards developing new methods for the treatment and control of flystrike. [ABSTRACT FROM AUTHOR]