CS/PB/BSCB 726 : Problems and perspective in computational molecular biology

Spring 2004 Faculty: Andrew Clark, Ron Elber and Uri Keich

Organizational meeting: Monday January 26, 4:30PM, RH 484

First lecture Monday Feb 9 2:30-3:30. Ron Elber will present the paper:

O. Teodorescu, T. Galor, J. Pillardy, and R. Elber, "Enriching the sequence substitution matrix by structural information" Proteins: Structure, Function and Bioinformatics, 54,41-48(2004)

Monday February 16, 2:30-3:30, Helgi Ingolfsson will present

 X. Liu, and W. Wang, "The number of protein folds and their distribution over families in nature", Proteins 54,491-499(2004)

Monday February 23, 2:30-3:30, Shobhit Varshney will present

Friedman N, Linial M, Nachman I, Pe'er D. (2000). Using Bayesian networks to analyze expression data. J Comput Biol. 7, 601-20.

Monday March 1, 2:30-3:30, Sung-Wook Chi will present

Haiyuan Yu, Nicholas M Luscombe, Jiang Qian and Mark Gerstein Genomic analysis of gene expression relationships in transcriptional regulatory networks, Trends in Genetics  19: 422-427

More reading is available in

Lee, T.I. et al. (2002) Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298, 799–804

Qian, J. et al. (2001) Beyond synexpression relationships: local clustering of time-shifted and inverted gene expression profiles identifies new, biologically relevant interactions. J. Mol. Biol. 314, 1053–1066

Monday, March 8, Anthony Faradjian will present

T. R. Weikl et al.  "Cooperativity in two-state protein folding kinetics", Protein Science (2004), 13:822–829.

Monday, March 15, Matthew Stedinger will present

Yan Yuan Tseng and Jie Liang, "Are residues in a protein folding nucleus evolutionary conserved", J. Mol. Biol. 335,869-880(2004)

Monday, April 5, Dr. Eric Xing from UC Berkeley who is a BSCB candidate will give a talk on

Probabilistic graphical models and algorithms for genomic analysis

Dr. Xing's talk will be held in A106 Mudd Hall between 2-3 PM.

I discuss two probabilistic modeling problems arising in metazoan genomic analysis: identifying motifs and cis-regulatory modules (CRMs) from transcriptional regulatory DNA sequences, and inferring haplotypes from genotypes of single nucleotide polymorphisms. Motif and CRM identification is important for understanding the gene regulatory network underlying metazoan development and functioning. I discuss a modular Bayesian model that captures rich structural characteristics of the transcriptional regulatory sequences and supports a variety of tasks such as learning motif representations, model-based motif and CRM prediction, and de novo motif detection. Haplotype inference is essential for the understanding of genetic variation within and among populations, with important applications to the genetic analysis of disease propensities and other complex traits. I discuss a Bayesian model based on a prior constructed from a Chinese restaurant process -- a nonparametric prior which provides control over the size of the unknown pool of population haplotypes, and on a likelihood that allows statistical errors in the haplotype/genotype relationship. Our models use the "probabilistic graphical model" formalism, a formalism that exploits the conjoined talents of graph theory and probability theory to build complex models out of simpler pieces. I discuss the mathematical underpinnings for the models, how they formally incorporate biological prior knowledge about the data, and the related computational issues.

...sorry, no pizzas...

Monday April 12, Anat Maoz will present:

Y. Levy, P.G. Wolynes and J. N. Onuchic, "Protein topology determines binding mechanisms", Proc. Natl. Acad. Sci. USA 101,511-516(2004)

Pizza will be served

Monday April 19, Amrita Basu, Topic TBA

Monday April 26, Yonatan Ben-Simhon, "How prevalent is functional alternative splicing in the human genome?" (http://www.cs.cornell.edu/Courses/cs726/2004sp/andy_suggestions/altsplice.pdf) And "Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays" (http://www.sciencemag.org/cgi/reprint/302/5653/2141.pdf).

This ongoing seminar series is based on student presentation of timely papers in computational biology.

Students are required to meet the faculty suggesting the paper at least a week in advance to their presentation.

Andy's suggestions:

1. Guri Giaever, Patrick Flaherty, Jochen Kumm, Michael Proctor, Corey Nislow, Daniel F. Jaramillo, Angela M. Chu, Michael I. Jordan, Adam P. Arkin, and Ronald W. Davis Chemogenomic profiling: Identifying the functional interactions of small molecules in yeast PNAS 2004 101: 793-798.

2. Yi-Kuo Yu, John C. Wootton, and Stephen F. Altschul The compositional adjustment of amino acid substitution matrices PNAS 2003 100: 15688-15693.

3. Andrew P. Morris, John C. Whittaker, Chun-Fang Xu, Louise K. Hosking, and David J. Balding Multipoint linkage-disequilibrium mapping narrows location interval and identifies mutation heterogeneity PNAS 2003 100: 13442-13446

4. Hong Qin, Henry H. S. Lu, Wei B. Wu, and Wen-Hsiung Li Evolution of the yeast protein interaction network PNAS 2003 100: 12820-12824.

5. W. James Kent, Robert Baertsch, Angie Hinrichs, Webb Miller, and David Haussler Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes PNAS 2003 100: 11484-11489.

6. Rotem Sorek, Ron Shamir and Gil Ast How prevalent is functional alternative splicing in the human genome?  Trends in Genetics, 20:68-71

7. Haiyuan Yu, Nicholas M Luscombe, Jiang Qian and Mark Gerstein Genomic analysis of gene expression relationships in transcriptional regulatory networks, Trends in Genetics  19: 422-427

8. Kira S. Makarova, Yuri I. Wolf and Eugene V. Koonin Potential genomic determinants of hyperthermophily, Trends in Genetics 19: 172-176

9. Brem RB, Yvert G, Clinton R, Kruglyak L. Genetic dissection of transcriptional regulation in budding yeast. Science. 2002   296: 752-755.

10. Cordell HJ. Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans. Hum Mol Genet. 2002  11: 2463-8.

Ron's suggestions:

1. Yan Yuan Tseng and Jie Liang, "Are residues in a protein folding nucleus evolutionary conserved", J. Mol. Biol. 335,869-880(2004)

2. H. W. T. van Vlijmen, A. Gupta, L. S. Narasimhan, and J. Singh, "A novel database of disulfide patterns and its application to the discovery of distantly related homologs", J. Mol. Biol. 335,1083-1092(2004)

3.     J.M. Dugan and R.B. Altman, "Using surface envelopes for discrimination of molecular models", Protein Science 13,15-24(2004)

4. X. Liu, and W. Wang, "The number of protein folds and their distribution over families in nature", Proteins 54,491-499(2004)

5. Y. Levy, P.G. Wolynes and J. N. Onuchic, "Protein topology determines binding mechanisms", Proc. Natl. Acad. Sci. USA 101,511-516(2004)

 Uri's suggestions