Schedule & Readings

1. Introduction to Molecular & Systems Biology (Thu, 8/28)
   Life, cell, genes, DNA, RNA, proteins, structure, function, evolution, cellular signaling, metabolism, genetic regulation, organization and dynamics, modularity.
   
   • L. Hunter, Life and its molecules: A brief introduction", AI Magazine, 2004.
   • H. Kitano, Systems biology: A brief overview, Science, 2002.


2. DNA Microarrays (Tue, 9/2)
   DNA microarray technology, oligonucleotide arrays, cDNA arrays, normalization and transformation of micorarray data.
   
   • A. Schulze & J. Downward, Navigating gene expression using microarrays: A technology review, Nature Cell Biology, 2001.
   • J. Quackenbush, Microarray data normalization and transformation, Nature Genetics, 2002.


3. Analysis of Gene Expression Data (Thu, 9/4; Thur, 9/11; Mon 9/15)
   Pattern discovery, clustering, biclustering, SVD, differential gene expression, classification, functional annotation, gene selection.
   • G. Sherlock, Analysis of large-scale gene expression data, Briefings in Bioinformatics, 2001.
   • D. K. Slonim, From patterns to pathways: Gene expression data analysis comes of age, Nature Genetics, 2002.
   Discussion Papers:
   • O. Alter, P. O. Brown, and D. Botstein, Generalized singular value decomposition for comparative analysis of genome-scale expression datasets of two different organisms, PNAS, 2003.
     Presented by: Robert W. Shields (Tue, 9/9)
   • D. P. Chen, S. C. Weber, P. S. Constantinou, T. A. Ferris, H. J. Lowe, and A. Butte, Novel integration of hospital electronic medical records and gene expression measurements to identify genetic markers of maturation, Pacific Symposium on Biocomputing, 2008.
     Presented by: Davis C. Ryman (Mon, 9/15)


4. Cellular Signaling & Genetic Regulation (Tue, 9/23)
   Signal transduction, control layer of the cell, combinatorics of cellular signaling, regulation of gene expression, regulatory network inference.
   • J. A. Papin, T. Hunter, B. O. Palsson, and S. Subramaniam, Reconstruction of cellular signalling networks and analysis of their properties, Nature Reviews Molecular Cell Biology, 2005.
   • T. Schlitt and A. Brazma, Current approaches to gene regulatory network modelling, BMC Bioinformatics, 2007.
   Discussion paper:
   • K. Sachs, O. Perez, D. Pe'er, D. A. Lauffenburger, and G. P. Nolan, Causal protein-signaling networks derived from multiparameter single-cell data , Science, 2005.
     Presented by: Michael Schnetz (Tue, 9/30)


5. Metabolic Networks (Thu, 9/25; Thu, 10/2)
   Metabolism, enzymes, representation of metabolic processes, pathway databases, stoichiometrics, flux analysis.
   • J. A. Papin, N. D. Price, S. J. Wiback, D. A. Fell, and B. O. Palsson, Metabolic pathways in the post-genome era, Trends in Biochemical Sciences, 2003.
   • J. Ihmels, R. Levy, and N. Barkai, Principles of transcriptional control in the metabolic network of saccharomyces cerevisiae, Nature Biotechnology, 2004.
   Discussion paper:
   • T. Shlomi, M.N Cabili, M.J. Herrgard, B.O. Palsson, and E. Ruppin, Network-based prediction of human tissue-specific metabolism, Nature Biotechnology, 2008.
     Presented by: Ching-Yi Wu (Tue, 10/7)


6. Protein Interaction Networks (Thu, 10/2; Thu, 10/9; Tue 10/14)
   Protein-protein interactions, high-throughput screening of protein interactions (Y2H, TAP), computational prediction of protein interactions, domain-domain interactions.
   • P. Aloy and R. B. Russell, Structural systems biology: modelling protein interactions, Nature Reviews Molecular Cell Biology, 2006.
   • B. A. Shoemaker and A. R. Panchenko, Deciphering Protein-Protein Interactions. Part I. Experimental Techniques and Databases. Part II. Computational Methods to Predict Protein and Domain Interaction Partners, PLoS Computational Biology, 2007.
Discussion paper:
• K. Guimaraes and T. M. Przytycka, Interrogating domain-domain interactions with parsimony based approaches, BMC Bioinformatics, 2008.
  Presented by: Gokhan Yavas (Thu, 10/16)
  


7. Topological Properties of Molecular Networks (Tue 10/23)
   Degree distribution, clustering coefficient, scale-free networks, hierarchy, modularity, topological motifs, robustness.
   • A. L. Barabasi and Z. N. Oltvai, Network biology: Understanding the cell's functional organization, Nature Reviews Genetics, 2004.
   • R. Milo, S. Shen-Orr, S. Itzkovitz, N. Kashtan, D. Chklovskii, and U. Alon, Network motifs: Simple building blocks of complex networks, Science, 2002.
   Discussion paper:
   • M. Middendorf, E. Ziv, and C. Wiggins, Inferring network mechanisms: The Drosophila melanogaster protein interaction network, PNAS, 2005.
     Presented by: Matthew Hayes (Tue, 10/28)


8. Computational Analysis of Molecular Networks (Thu, 10/30; Thu, 11/6)
   Reconstructing signaling networks, identification of functional modules, network clustering, modular decomposition of networks, identification of signaling pathways.
   • B. S. Srinivasan, N. H. Shah, J. A. Flannick, E. Abeliuk, A. F. Novak, and S. Batzoglou, Current progress in network research: toward reference networks for key model organisms", Briefings in Bioinformatics, 2007.
   • R. Sharan and T. Ideker, Modeling cellular machinery through biological network comparison, Nature Biotechnology, 2006.
   • R. Sharan, I. Ulitsky, and R. Shamir. Network based prediction of protein function, Molecular Systems Biology, 2007.
   Discussion Paper:
   • M. Kirac and G. Ozsoyoglu, Protein function prediction based on patterns in biological networks, RECOMB, 2008.
     Presented by: Wei Jin (Tue, 11/4)


9. Dynamics of Molecular Networks, Phenotype, and Disease (Tue, 11/11)
   Temporal and spatial variability in networks, manifestation of genetic interactions in molecular networks, network assisted identification of disease genes, network based analysis of differential expression, proteomics, integration of omics datasets.
   • A. R. Joyce and B. O. Palsson, The model organism as a system: integrating 'omics' data sets, Nature Reviews Molecular Cell Biology, 2006.
   • T. Ideker and R. Sharan, Protein networks in disease,Genome Research, 2008.
   Discussion Papers:
   1. R. Kelley and T. Ideker, Systematic interpretation of genetic interactions using protein networks, Nature Biotechnology, 2005.
      Presented by: Elizabeth Rodkey (Thu, 11/13)
   2. L. M. F. de Godoy et al. Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast, Nature, 2008.
      Presented by: Michael Schnetz (Thu, 11/20)
   3. H.-Y. Chuang, E. Lee, Y.-T. Liu, D. Lee, and T. Ideker, Network-based classification of breast cancer metastasis, Molecular Systems Biology, 2007.
   4. J. Watkinson, X. Wang, T. Zheng, and D. Anastassiou, Identification of gene interactions associated with disease from gene expression data using synergy networks, BMC Systems Biology, 2008.
   
   
10. Systems Biology of Memory
    Discussion papers:
    1. M. Costa-Mattioli, Switching memories on and off, Science, 2008.
    2. A. D. Wagner, Building memories: Remembering and forgetting of verbal experiences as predicted by brain activity, Science, 2008.
    Presented by: Ching-Yi Wu (Tue, 11/25)

Class Meeting

TTh 2:45pm-4:00pm, NORD 204

Office Hours

TTh 1:30pm-2:30pm, OLIN 512

Instructor

Mehmet Koyuturk

Description

Bioinformatics is the science of making sense of biological information. In the post-genomic era, algorithmic and computational methods for organizing, integrating, analyzing, and querying biological data prove invaluable. Today, availability of high-throughput data relating to the interactions between biomolecules, coupled with past accomplishments in molecular biology, make it possible to study the cell at the systems level, commonly through network models. In this course, we cover cutting-edge algorithmic, analytical, and statistical techniques used to effectively analyze these novel sources of biological data. This semester, the main theme of the course will be "molecular networks in disease".