Improved strategy for the curation and classification of kinases, with broad applicability to other eukaryotic protein groups

Stroehlein, Andreas J.; Young, Neil D.; Gasser, Robin B.

doi:10.1038/s41598-018-25020-8

Cited by 12 publications

(11 citation statements)

References 81 publications

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“…In this study, our established bioinformatics workflow [63] assisted in the prediction of a conserved set (family) of C. sinensis NPC2-like proteins. Evidence that two pairs of NPC2-like protein orthologues (Cs-k2.gene11598/ csin11538 and Cs-k2.gene9726/csin101111) undergo positive selection [17] lends support for a recent expansion of this protein family.…”

Section: Discussionmentioning

confidence: 99%

Expanded complement of Niemann-Pick type C2-like protein genes in Clonorchis sinensis suggests functions beyond sterol binding and transport

et al. 2020

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Background: The parasitic flatworm Clonorchis sinensis inhabits the biliary tree of humans and other piscivorous mammals. This parasite can survive and thrive in the bile duct, despite exposure to bile constituents and host immune attack. Although the precise biological mechanisms underlying this adaptation are unknown, previous work indicated that Niemann-pick type C2 (NPC2)-like sterol-binding proteins might be integral in the host-parasite interplay. Expansions of this family in some invertebrates, such as arthropods, have shown functional diversification, including novel forms of chemoreception. Thus, here we curated the NPC2-like protein gene complement in C. sinensis, and predicted their conserved and/or divergent functional roles. Methods: We used an established comparative genomic-bioinformatic approach to curate NPC2-like proteins encoded in published genomes of Korean and Chinese isolates of C. sinensis. Protein sequence and structural homology, presence of conserved domains and phylogeny were used to group and functionally classify NPC2-like proteins. Furthermore, transcription levels of NPC2-like protein-encoding genes were explored in different developmental stages and tissues. Results: Totals of 35 and 32 C. sinensis NPC2-like proteins were predicted to be encoded in the genomes of the Korean and Chinese isolates, respectively. Overall, these proteins had low sequence homology and high variability of sequence alignment coverage when compared with curated NPC2s. Most C. sinensis proteins were predicted to retain a conserved ML domain and a conserved fold conformation, with a large cavity within the protein. Only one protein sequence retained the conserved amino acid residues required in bovine NPC2 to bind cholesterol. Non-canonical C. sinensis NPC2-like protein-coding domains clustered into four distinct phylogenetic groups with members of a group frequently encoded on the same genome scaffolds. Interestingly, NPC2-like protein-encoding genes were predicted to be variably transcribed in different developmental stages and adult tissues, with most being transcribed in the metacercarial stage. Conclusions: The results of the present investigation confirms an expansion of NPC2-like proteins in C. sinensis, suggesting a diverse array of functions beyond sterol binding and transport. Functional explorations of this protein family

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Section: Discussionmentioning

confidence: 99%

Expanded complement of Niemann-Pick type C2-like protein genes in Clonorchis sinensis suggests functions beyond sterol binding and transport

et al. 2020

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“…Gene models were curated employing protein domain architecture information from the InterPro database (release 75.0) and from transcriptomic data. Kinase gene models were curated using an established approach [ 92 ]–i.e. kinases were first inferred and classified into groups, families and subfamilies using Kinannote [ 93 ], and the PANTHER [ 94 ] and InterPro databases were then employed for unclassified kinases.…”

Section: Methodsmentioning

confidence: 99%

High-quality nuclear genome for Sarcoptes scabiei—A critical resource for a neglected parasite

Korhonen

Gasser

et al. 2020

PLoS Negl Trop Dis

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The parasitic mite Sarcoptes scabiei is an economically highly significant parasite of the skin of humans and animals worldwide. In humans, this mite causes a neglected tropical disease (NTD), called scabies. This disease results in major morbidity, disability, stigma and poverty globally and is often associated with secondary bacterial infections. Currently, anti-scabies treatments are not sufficiently effective, resistance to them is emerging and no vaccine is available. Here, we report the first high-quality genome and transcriptomic data for S . scabiei . The genome is 56.6 Mb in size, has a a repeat content of 10.6% and codes for 9,174 proteins. We explored key molecules involved in development, reproduction, host-parasite interactions, immunity and disease. The enhanced ‘omic data sets for S . scabiei represent comprehensive and critical resources for genetic, functional genomic, metabolomic, phylogenetic, ecological and/or epidemiological investigations, and will underpin the design and development of new treatments, vaccines and/or diagnostic tests.

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“…1 ). Additionally, the quality of draft genomes is continually evolving, mainly due to concerted curation efforts by individual curators and the scientific community [ 23 , 51 , 52 ]. Taken together, the differences in the amount and quality of data that were integrated into the prioritisation approaches is likely to have led to some discrepancies in the prediction of drug targets between the present and earlier studies.…”

Section: Discussionmentioning

confidence: 99%

Interactive online application for the prediction, ranking and prioritisation of drug targets in Schistosoma haematobium

et al. 2018

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BackgroundHuman schistosomiasis is a neglected tropical disease caused by parasitic worms of the genus Schistosoma that still affects some 200 million people. The mainstay of schistosomiasis control is a single drug, praziquantel. The reliance on this drug carries a risk of resistance emerging to this anthelmintic, such that research towards alternative anti-schistosomal drugs is warranted. In this context, a number of studies have employed computational approaches to prioritise proteins for investigation as drug targets, based on extensive genomic, transcriptomic and small-molecule data now available.MethodsHere, we established a customisable, online application for the prioritisation of drug targets and applied it, for the first time, to the entire inferred proteome of S. haematobium. This application enables selection of weighted and ranked proteins representing potential drug targets, and integrates transcriptional data, orthology and gene essentiality information as well as drug-drug target associations and chemical properties of predicted ligands.ResultsUsing this application, we defined 25 potential drug targets in S. haematobium that associated with approved drugs, and 3402 targets that (although they could not be linked to any compounds) are conserved among a range of socioeconomically important flatworm species and might represent targets for new trematocides.ConclusionsThe online application developed here represents an interactive, customisable, expandable and reproducible drug target ranking and prioritisation approach that should be useful for the prediction of drug targets in schistosomes and other species of parasitic worms in the future. We have demonstrated the utility of this online application by predicting potential drug targets in S. haematobium that can now be evaluated using functional genomics tools and/or small molecules, to establish whether they are indeed essential for parasite survival, and to assist in the discovery of novel anti-schistosomal compounds.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-3197-6) contains supplementary material, which is available to authorized users.

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Improved strategy for the curation and classification of kinases, with broad applicability to other eukaryotic protein groups

Cited by 12 publications

References 81 publications

Expanded complement of Niemann-Pick type C2-like protein genes in Clonorchis sinensis suggests functions beyond sterol binding and transport

Expanded complement of Niemann-Pick type C2-like protein genes in Clonorchis sinensis suggests functions beyond sterol binding and transport

High-quality nuclear genome for Sarcoptes scabiei—A critical resource for a neglected parasite

Interactive online application for the prediction, ranking and prioritisation of drug targets in Schistosoma haematobium

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