Sunday, April 27, 2008

Abstract for talk [I:ISMB08-SS] Special Session at ISMB-2008 on 21 July 2008


Understanding Protein Function on a Genome-scale using Networks

Mark Gerstein

Yale University

My talk will be concerned with topics in proteomics, in particular
predicting protein function on a genomic scale. We approach this
through the prediction and analysis of biological networks, focusing
on protein-protein interaction and transcription-factor-target ones. I
will describe how these networks can be determined through integration
of many genomic features and how they can be analyzed in terms of
various simple topological statistics. In particular, I will discuss a
number of specific analyses: (1) Integrating gene expression data with
the regulatory network illuminates transient hubs; (2) Integration of
the protein interaction network with 3D molecular structures reveals
different types of hubs, depending on the number of interfaces
involved in interactions (one or many); (3) Analysis of betweenness in
biological networks reveals that this quantity is more strongly
correlated with essentially than degree; (4) Analysis of structure of
the regulatory network shows that it has a hierarchiel layout with the
"middle-managers" acting as information bottlenecks. (5) Development
of a useful web-based tools for the analysis of networks, TopNet and

Integrated prediction of the helical membrane protein interactome in
yeast. Y Xia, LJ Lu, M Gerstein (2006) J Mol Biol 357: 339-49.

Relating three-dimensional structures to protein networks provides
evolutionary insights. PM Kim, LJ Lu, Y Xia, MB Gerstein (2006)
Science 314: 1938-41.

The tYNA platform for comparative interactomics: a web tool for
managing, comparing and mining multiple networks. KY Yip, H Yu, PM
Kim, M Schultz, M Gerstein (2006) Bioinformatics 22: 2968-70.

The importance of bottlenecks in protein networks: correlation with
gene essentiality and expression dynamics. H Yu, PM Kim, E Sprecher,
V Trifonov, M Gerstein (2007) PLoS Comput Biol 3: e59.

Genomic analysis of the hierarchical structure of regulatory networks.
H Yu, M Gerstein (2006) Proc Natl Acad Sci U S A 103: 14724-31.

The role of disorder in interaction networks: a structural analysis.
PM Kim, A Sboner, Y Xia, M Gerstein (2008) Mol Syst Biol 4: 179.

Positive selection at the protein network periphery: evaluation in terms of
structural constraints and cellular context.
PM Kim, JO Korbel, MB Gerstein (2007) Proc Natl Acad Sci U S A 104: 20274-9.

Wednesday, April 9, 2008

abstract for talk at Center For Computational Biology & Bioinformatics at Indiana U. on 28-Apr 2008 [I:IUPUI]

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

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.

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.

The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they?
D Zheng, MB Gerstein (2007) Trends Genet 23: 219-24. a comprehensive database and comparison platform for pseudogene
JE Karro, Y Yan, D Zheng, Z Zhang, N Carriero, P Cayting, P Harrrison, M
Gerstein (2007) Nucleic Acids Res 35: D55-60.

A computational approach for identifying pseudogenes in the ENCODE regions.
D Zheng, MB Gerstein (2006) Genome Biol 7 Suppl 1: S13.1-10.

The real life of pseudogenes.
M Gerstein, D Zheng (2006) Sci Am 295: 48-55.

PseudoPipe: an automated pseudogene identification pipeline.
Z Zhang, N Carriero, D Zheng, J Karro, PM Harrison, M Gerstein (2006)
Bioinformatics 22: 1437-9.

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.