Kinase annotation for helminths

doi:10.1038/protex.2018.042

Method Article

Kinase annotation for helminths

https://doi.org/10.1038/protex.2018.042

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posted 17 May, 2018

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A method to annotate kinase domains in nematodes and platyhelminths by using dynamic thresholds for different kinase groups.

Computational biology and bioinformatics

Biotechnology

kinase annotation

genome annotation

kinase

kinome

kinase domain

helminths

nematoda

platyhelminthes

Kinases are one of the most common types of targets for existing drugs for human diseases¹ and are considered strong candidates for the development of new ones. This method was developed to annotate kinase domains in the gene sets of nematodes and platyhelminths by aligning to the Kinomer profile database² using carefully considered scoring thresholds specific to each kinase group.

kinase domain models from kinomer
installation of HMMER v2.3.2

Download the Kinase domain models file from the Kinomer website ( " http://www.compbio.dundee.ac.uk/kinomer/allPK.hmm":http://www.compbio.dundee.ac.uk/kinomer/allPK.hmm).
Kinase class specific score thresholds are determined by starting with those used in the Kinomer paper³ and then adjusting them until an hmmpfam search (HMMER v2.3.2) comes as close as possible to identifying all known C. elegans kinases using the Kinomer allPK.hmm profile database. e.g. The final cutoffs used for the associated publication were: TK, 5.5e-03; CAMK, 9.6e-07; CK1, 1.1e-02; CMGC, 6.7e-03; AGC, 1.1e-14; STE, 3.4e-03; RGC, 4.8e-05; TKL, 8.7e-03; PDHK, 4.7e-160; PIKK, 1.4e-06; Alpha, 8.5e-66; and RIO, 7.5e-10.
Hmmpfam is used with default settings to map the user provided gene protein sequences against the Kinomer models.
Genes with hmmpfam 'hits' meeting the kinase class specific custom cutoffs are then annotated as a putative kinase of the given class.

A set of annotated kinase genes with the corresponding domain annotations

Santos, R. et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov 16, 19-34, doi:10.1038/nrd.2016.230 (2017).
Kinomer URL: "http://www.compbio.dundee.ac.uk/kinomer/allPK.hmm":http://www.compbio.dundee.ac.uk/kinomer/allPK.hmm
Diego Miranda-Saavedra and Geoffrey J. Barton, Classification and functional annotation of eukaryotic protein kinases. Proteins 68:893-914 (2007)

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Kinase annotation for helminths

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