Kinannote, a computer program to identify and classify members of the eukaryotic protein kinase superfamily

Motivation: Kinases of the eukaryotic protein kinase superfamily are key regulators of most aspects eukaryotic cellular behavior and have provided several drug targets including kinases dysregulated in cancers. The rapid increase in the number of genomic sequences has created an acute need to identify and classify members of this important class of enzymes efficiently and accurately. Results: Kinannote produces a draft kinome and comparative analyses for a predicted proteome using a single line command, and it is currently the only tool that automatically classifies protein kinases using the controlled vocabulary of Hanks and Hunter [Hanks and Hunter (1995)]. A hidden Markov model in combination with a position-specific scoring matrix is used by Kinannote to identify kinases, which are subsequently classified using a BLAST comparison with a local version of KinBase, the curated protein kinase dataset from www.kinase.com. Kinannote was tested on the predicted proteomes from four divergent species. The average sensitivity and precision for kinome retrieval from the test species are 94.4 and 96.8%. The ability of Kinannote to classify identified kinases was also evaluated, and the average sensitivity and precision for full classification of conserved kinases are 71.5 and 82.5%, respectively. Kinannote has had a significant impact on eukaryotic genome annotation, providing protein kinase annotations for 36 genomes made public by the Broad Institute in the period spanning 2009 to the present. Availability: Kinannote is freely available at http://sourceforge.net/projects/kinannote. Contact: jmgold@broadinstitute.org Supplementary information: Supplementary data are available at Bioinformatics online.

[1]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[2]  Jennifer D. Artz,et al.  The Cryptosporidium parvum Kinome , 2011, BMC Genomics.

[3]  Todd H. Oakley,et al.  The Amphimedon queenslandica genome and the evolution of animal complexity , 2010, Nature.

[4]  Karen E. Pilcher,et al.  The Dictyostelium Kinome—Analysis of the Protein Kinases from a Simple Model Organism , 2006, PLoS genetics.

[5]  Christina A. Cuomo,et al.  Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth , 2012, Genome research.

[6]  G. Beakes,et al.  The evolutionary phylogeny of the oomycete “fungi” , 2011, Protoplasma.

[7]  D. Richter,et al.  Origin of metazoan cadherin diversity and the antiquity of the classical cadherin/β-catenin complex , 2012, Proceedings of the National Academy of Sciences.

[8]  Narayanaswamy Srinivasan,et al.  KinG: a database of protein kinases in genomes , 2004, Nucleic Acids Res..

[9]  S. Henikoff,et al.  Amino acid substitution matrices from protein blocks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Srinivasan,et al.  Analysis of the protein kinome of Entamoeba histolytica , 2008, Proteins.

[11]  D. S. Reiner,et al.  The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology , 2011, Genome Biology.

[12]  D. Hibbett,et al.  The search for the fungal tree of life. , 2009, Trends in microbiology.

[13]  D. Roos,et al.  Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses. , 2010, Cell host & microbe.

[14]  Jeremy Zucker,et al.  Genomics of Loa loa, a Wolbachia-free filarial parasite of humans , 2013, Nature Genetics.

[15]  T. C. White,et al.  Generating and Testing Molecular Hypotheses in the Dermatophytes , 2008, Eukaryotic Cell.

[16]  Bin Zhang,et al.  PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse , 2011, Nucleic Acids Res..

[17]  P E Bourne,et al.  The protein kinase resource. , 1997, Trends in biochemical sciences.

[18]  Bernhard Hemmer,et al.  A point mutation in PTPRC is associated with the development of multiple sclerosis , 2000, Nature Genetics.

[19]  Geoffrey J. Barton,et al.  Kinomer v. 1.0: a database of systematically classified eukaryotic protein kinases , 2008, Nucleic Acids Res..

[20]  Christina A. Cuomo,et al.  Comparative Genome Analysis of Trichophyton rubrum and Related Dermatophytes Reveals Candidate Genes Involved in Infection , 2012, mBio.

[21]  Christina A. Cuomo,et al.  Obligate Biotrophy Features Unraveled by the Genomic Analysis of the Rust Fungi, Melampsora larici-populina and Puccinia graminis f. sp. tritici , 2011 .

[22]  L. Johnson.  Protein kinase inhibitors: contributions from structure to clinical compounds , 2009, Quarterly Reviews of Biophysics.

[23]  Natarajan Kannan,et al.  Structural and evolutionary divergence of eukaryotic protein kinases in Apicomplexa , 2011, BMC Evolutionary Biology.

[24]  A. Fersht.  Enzyme structure and mechanism , 1977 .

[25]  S. Baldauf,et al.  The Deep Roots of Eukaryotes , 2003, Science.

[26]  Gerard Manning,et al.  The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan , 2008, Proceedings of the National Academy of Sciences.

[27]  A. F. Neuwald,et al.  Did protein kinase regulatory mechanisms evolve through elaboration of a simple structural component? , 2005, Journal of molecular biology.

[28]  Narmada Thanki,et al.  CDD: conserved domains and protein three-dimensional structure , 2012, Nucleic Acids Res..

[29]  K. Mockaitis,et al.  Arabidopsis kinome: after the casting , 2004, Functional & Integrative Genomics.

[30]  Wendy S. Beane,et al.  The sea urchin kinome: a first look. , 2006, Developmental biology.

[31]  G. Barton,et al.  The kinomes of apicomplexan parasites. , 2012, Microbes and infection.

[32]  T. Hunter,et al.  Evolution of protein kinase signaling from yeast to man. , 2002, Trends in biochemical sciences.

[33]  Christina A. Cuomo,et al.  Obligate biotrophy features unraveled by the genomic analysis of rust fungi , 2011, Proceedings of the National Academy of Sciences.

[34]  T. Hunter,et al.  The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification 1 , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[35]  Krys J. Kochut,et al.  ProKinO: An Ontology for Integrative Analysis of Protein Kinases in Cancer , 2011, PloS one.

[36]  Q. Zeng,et al.  Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus) , 2010, Proceedings of the National Academy of Sciences.

[37]  C. Stoeckert,et al.  OrthoMCL: identification of ortholog groups for eukaryotic genomes. , 2003, Genome research.

[38]  William H. Majoros,et al.  Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote , 2006, PLoS biology.

[39]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[40]  T. Hunter,et al.  The Protein Kinase Complement of the Human Genome , 2002, Science.

[41]  Philip E. Bourne,et al.  Structural Evolution of the Protein Kinase–Like Superfamily , 2005, PLoS Comput. Biol..

[42]  Charles E Metz,et al.  Receiver operating characteristic analysis: a tool for the quantitative evaluation of observer performance and imaging systems. , 2006, Journal of the American College of Radiology : JACR.

[43]  E. Koonin,et al.  Novel families of putative protein kinases in bacteria and archaea: evolution of the "eukaryotic" protein kinase superfamily. , 1998, Genome research.

[44]  I. Ruiz-Trillo,et al.  Molecular phylogeny of unikonts: new insights into the position of apusomonads and ancyromonads and the internal relationships of opisthokonts. , 2013, Protist.

[45]  A. Dash,et al.  The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum , 2012, Nature Genetics.

[46]  Manolis Kellis,et al.  Comparative Functional Genomics of the Fission Yeasts , 2011, Science.

[47]  E. Birney,et al.  Pfam: the protein families database , 2013, Nucleic Acids Res..