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Kristine Briedis Journal Club 17 April 2006

Systematic analysis of human kinase genes: a large number of genes and alternative splicing events result in functional and structural diversity Milanesi et al. BMC Bioinformatics Dec 2005. Kristine Briedis Journal Club 17 April 2006. Overview. Analysis of the human kinome

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Kristine Briedis Journal Club 17 April 2006

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  1. Systematic analysis of human kinase genes: a large number of genes and alternative splicing events result in functional and structural diversityMilanesi et al. BMC Bioinformatics Dec 2005 Kristine Briedis Journal Club 17 April 2006

  2. Overview • Analysis of the human kinome • Identification of alternative splice forms • Domain and structure analysis

  3. Kinase Gene Identification • Generated PSI-BLAST position specific scoring matrix from Manning’s kinome • Used PSSM with tBLASTn against all human chromosome sequences in NCBI (as of April 14, 2003) • Predicted kinase genes from BLAST hits using GenomeScan

  4. Claim to find five “new” kinase genes • One is annotated in NCBI as a kinase • Other four are annotated in NCBI as predicted genes that are “similar to…kinase” • One gene codes for a protein only 2 aa different from a kinase Manning already identified (on different chromosome) • Another gene identified codes for a protein only 48 aa long (according to Ensembl)

  5. Search for CSTs • Compared mouse and human orthologous kinase genes to identify small genomic conserved sequence tags (CSTs) • Theory: functional sequences evolve slower, thus CSTs shared between species may indicate exons or other regulatory elements • CST must be at least 100 bp long and 70% identity • Able to analyze 483 corresponding human-mouse sequences • Found roughly 35000 CSTs, which cover 8% of the selected human sequences • CSTs “mostly unique”; about half within analyzed kinase gene exons

  6. CST analysis • Annotated CSTs for: • GC% • Similarity between orthologs (gaps, sequence identity) • Location in gene • Known SNPs • Identification of motifs and signals (TF binding sites; RNA secondary structure; repeats) • Checked for possibility of being an unidentified exon • Open reading frames; codon usage; matches with GENSCAN exons • Human EST match • Mouse counterpart is annotated as exon • Mouse counterpart matches rodent EST

  7. Alternative Splice Events

  8. Domain and Structure Analysis

  9. KinWeb

  10. Summary • Presented findings of 5 “new” kinase genes • Apparent discovery of alternative splice forms • Domain and structure analysis

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