A central problem for 21st century science will be the annotation and
understanding of the human genome. My talk will be concerned with
topics within this area, in particular annotating pseudogenes (protein
fossils), binding sites, CNVs, and novel transcribed regions in the
genome. Much of this work has been carried out in the framework of the
ENCODE and modENCODE projects.
In particular, I will discuss how we identify regulatory regions and
novel, non-genic transcribed regions in the genome based on processing
of tiling array and next-generation sequencing experiments. I will
further discuss how we cluster together groups of binding sites and
novel transcribed regions.
Next, I will discuss a comprehensive pseudogene identification
pipeline and storage database we have built. This has enabled us to
identify >10K pseudogenes in the human and mouse genomes and analyze
their distribution with respect to age, protein family, and
chromosomal location. I will try to inter-relate our studies on
pseudogenes with those on transcribed 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 --
e.g., the construction of annotation pipelines, developing algorithms
for optimal tiling, and refining approaches for scoring microarrays.
http://bioinfo.mbb.yale.edu
http://pseudogene.org
http://tiling.gersteinlab.org
The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they?
D Zheng, MB Gerstein (2007) Trends Genet 23: 219-24.
Pseudogene.org: a comprehensive database and comparison platform for pseudogene
annotation.
JE Karro, Y Yan, D Zheng, Z Zhang, N Carriero, P Cayting, P Harrrison, M
Gerstein (2007) Nucleic Acids Res 35: D55-60.
The real life of pseudogenes.
M Gerstein, D Zheng (2006) Sci Am 295: 48-55.
Toward a universal microarray: prediction of gene expression through
nearest-neighbor probe sequence identification.
TE Royce, JS Rozowsky, MB Gerstein (2007) Nucleic Acids Res 35: e99.
Pseudogenes in the ENCODE regions: consensus annotation, analysis of
transcription, and evolution.
D Zheng, A Frankish, R Baertsch, P Kapranov, A Reymond, SW Choo, Y Lu, F
Denoeud, SE Antonarakis, M Snyder, Y Ruan, CL Wei, TR Gingeras, R Guigo, J
Harrow, MB Gerstein (2007) Genome Res 17: 839-51.
Statistical analysis of the genomic distribution and correlation of regulatory
elements in the ENCODE regions.
ZD Zhang, A Paccanaro, Y Fu, S Weissman, Z Weng, J Chang, M Snyder, MB Gerstein
(2007) Genome Res 17: 787-97.
The DART classification of unannotated transcription within the ENCODE regions:
associating transcription with known and novel loci.
JS Rozowsky, D Newburger, F Sayward, J Wu, G Jordan, JO Korbel, U Nagalakshmi, J
Yang, D Zheng, R Guigo, TR Gingeras, S Weissman, P Miller, M Snyder, MB Gerstein
(2007) Genome Res 17: 732-45.
What is a gene, post-ENCODE? History and updated definition.
MB Gerstein, C Bruce, JS Rozowsky, D Zheng, J Du, JO Korbel, O Emanuelsson, ZD
Zhang, S Weissman, M Snyder (2007) Genome Res 17: 669-81.
Systematic prediction and validation of breakpoints associated with copy-number
variants in the human genome.
JO Korbel, AE Urban, F Grubert, J Du, TE Royce, P Starr, G Zhong, BS Emanuel, SM
Weissman, M Snyder, MB Gerstein (2007) Proc Natl Acad Sci U S A 104: 10110-5.
Analysis of Copy Number Variants and Segmental Duplications in the Human Genome:
Evidence for a Change in the Process of Formation Mechanism in Recent
Evolutionary History
Philip M. Kim Hugo Y. K. Lam Alexander E. Urban, Jan Korbel, Xueying Chen,
Michael Snyder and Mark B. Gerstein
Genome Res. (in press, 2008)
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