for an e-briefing
Title: Human Genome Annotation
A central problem for 21st century science will be the analysis and understanding of the human genome. My talk will be concerned with topics within this area, in particular annotating pseudogenes (protein fossils) in the genome. I will discuss a comprehensive pseudogene identification pipeline and storage database we have built. This has enabled use to identify >10K pseudogenes in the human and mouse genomes and analyze their distribution with respect to age, protein family, and chromosomal location. One interesting finding is the large number of ribosomal pseudogenes in the human genome, with 80 functional ribosomal proteins giving rise to ~2,000 ribosomal protein pseudogenes. I will try to inter-relate our studies on pseudogenes with those on tiling arrays, which enable one to comprehensively probe the activity of intergenic regions. At the end I will bring these together, trying to assess the transcriptional activity of pseudogenes. Throughout I will try to introduce some of the computational algorithms and approaches that are required for genome annotation and tiling arrays -- i.e. the construction of annotation pipelines, developing algorithms for optimal tiling, and refining approaches for scoring microarrays.
Comparative analysis of processed pseudogenes in the mouse and human genomes. Z Zhang, N Carriero, M Gerstein (2004) Trends Genet 20: 62-7. Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. Z Zhang, PM Harrison, Y Liu, M Gerstein (2003) Genome Res 13: 2541-58. Patterns of nucleotide substitution, insertion and deletion in the human genome inferred from pseudogenes. Z Zhang, M Gerstein (2003) Nucleic Acids Res 31: 5338-48. Integrated pseudogene annotation for human chromosome 22: evidence for transcription. D Zheng, Z Zhang, PM Harrison, J Karro, N Carriero, M Gerstein (2005) J Mol Biol 349: 27-45. P. Bertone, F. Schubert, V. Trifonov, J. Rozowsky, O. Emanuelsson, J. Karro, M-Y Kao, M. Snyder, M. Gerstein. Design optimization methods for genomic DNA tiling arrays. Genome Research (in press). TE Royce, JS Rozowsky, P Bertone, M Samanta, V Stolc, S Weissman, M Snyder, M Gerstein (2005). "Issues in the analysis of oligonucleotide tiling microarrays for transcript mapping." Trends Genet 21: 466-75.