This is a protocol preprint. Preprints are preliminary reports that have not undergone peer review. They should not be considered conclusive, used to inform clinical practice, or referenced by the media as validated information.
Method Article
Kinase annotation for helminths
John Martin
Mitreva Lab (MGI, Washington University in St. Louis)
Corresponding Author
License:
This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License
A method to annotate kinase domains in nematodes and platyhelminths by using dynamic thresholds for different kinase groups.
Keywords
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)
Version History
CURRENT STATUS: Posted
Version 1
Posted 17 May, 2018
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Method Article
Kinase annotation for helminths
John Martin
Mitreva Lab (MGI, Washington University in St. Louis)
Corresponding Author
Version History
CURRENT STATUS: Posted
Version 1
Posted 17 May, 2018
Metrics
Comments: 0
HTML Views: ...
License:
This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License
A method to annotate kinase domains in nematodes and platyhelminths by using dynamic thresholds for different kinase groups.
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)