BNFO 301 
Introduction to Bioinformatics
Topic: Genome Analysis
Spring 2011 

Rationale

OK, this is the main event.

Why 'What is a Gene'? Why codons? Why BioBIKE? All of that so that you could be prepared for the analysis of mycobacterial phage genomes, a project that will consume most of the remainder of the semester. The goal of this unit is to give you an introduction to bacteriophage genome analysis and the specific areas of analysis that will be of most interest to us.

There's too much to learn about genome analysis. There's WAY too much to learn. Never mind you, there's too much for ME to learn, or any other human for that matter. Fortunately, humans have made significant progress despite the fact that no single human is an expert in all areas. The strategy for your research project is similar to the strategy for all large research projects: each person becomes expert in a small slice of the pie and conversent about other people's slices. Each person contributes to the whole, even though the whole is too big for any single person to comprehend.

Readings, Tours, and Investigations
    Tour:
        Search for FMRP in Drosophila.
        The flavors of BLAST and their nature

    Reading and Tour:
        Comparative genomics of the mycobacteriophages: Insights into bacteriophage evolution.
        Hatfull GF, Cresawn SG, Hendrix RW (2008). Research in Microbiology 159:332-339.
        Tour: Part I and Part II

    Reading and Tour: (may be changed)
        The phage proteomic tree: A genome-based taxonomy for phage.
        Rohwer F, Edwards R (2002). Journal of Bacteriology 184:4529-4535. (+ tour)

    Reading and Tour: (may be changed)
        In silico analysis of mycobacteriophage Che12 genome: Characterization of genes
        required to lysogenise Mycobacterium tuberculosis.
        Gomathi NS, Sameer H, Kumar V, Balaji S, Azger Dustackeer VN, Narayana PR (2007).
        Computational Biology and Chemistry 31:82-91. (+ tour)

    Reading and Tour: (may be changed)
        Detecting anomalous gene clusters and pathogenicity islands in diverse bacterial genomes
        Karlin S (2001).
        Trends in Microbiology 9:335-343. (+ tour)

    Tour:
        Was Mendel Right? (Part I and Part II )

Problem Sets
    Problem Set 4: Loops and Mapping (Target date February 25)
    Problem Set 5: Genome Analysis (Target date March 4)
    Problem Set 6: Statistics (Target date March 11)

Analysis Groups (may be changed; times shown are for illustration only)
Each group is defined by a core focus, which comes with a suggested article. Group members may use this article as inspiration, a starting point to find other pertinent articles, and an aid in defining and subdividing the project. A group is under no obligation to stick to any predetermined agenda, so long as it goes in a direction that is even more interesting than the original.

  • Wally Annotation Group (Groups 1, 2, 3. 4)
    Find genes in sequence, function in genes, sense in noncoding regions
    Compare with genes and features of other phages
     
  • Batiatus Annotation Group (Groups 5, 6)
    Find genes in sequence, function in genes, sense in noncoding regions
    Compare with genes and features of other phages
     
  1. Lysogeny Group (Group 1, Wed 3 PM: Ben, Sherrif, Ankur, Won Je, Kamya)
    Do the new phages have protein indicative of a lysogenic life style? Other mycobacteriophage?
    Can the sites of integration and repression of lytic expression be identified?
            The lysis-lysogeny decision of phage lambda: Explicit programming and responsiveness
            Ira Herskowitz (1980).
            Annual Review of Genetics 14:339-445.
     
  2. Lysis Group (Group 6, Mon 5 PM: Candi, Danielle D, Stephanie, Danielle R, Rich)
    What functions do the new phages have to lyse their hosts? Other mycobacteriophage?
    How is the moment of lysis controlled?
            Phages will out: Strategies of host cell lysis
            Ry Young, Ing-Nang Wang, William D Roof (2000). Trends in Microbiology 8:120-128.
     
  3. Sequence Bias Group (Group 5, Wed 9 AM: Hassan, Ross, Eiman, Max, Christopher)
    Do the new genomes exhibit oligonucleotide frequencies that can't be explained by chance?
    Do the phage sequence biases match those of their presumed bacterial hosts?
    What tRNAs do the phage have? Is codon biases influenced by those tRNAs?
            Codon usages in different gene classes of the Escherichia coli genome.
            Samuel Karlin, Jan Mrázek, Allan M Campbell (1998). Molecular Microbiology 29:1341-1355.
     
  4. Mobile Element Group (Group 3, Tue 12:30 PM: Thanh, Payal, Amy, Doug)
    Do the new phages have sequences that appear capable of transposition? Other mycobacteriophage?
    What are the extents of the elements?
            Transposases are the most abundant, most ubiquitous genes in nature
            Ramy K Aziz, Mya Breitbart, Robert A Edwards (2010). Nucleic Acids Research 38:4207-4217.
     
  5. DNA replication group (Group 4, Wed 10 AM: Yohanes, Nick, Taquara, Mesay, Sophie)
    What proteins do the new phages have to support the replication of phage DNA? Other mycobacteriophage?
    What signals on the phage DNA serve to initiate DNA replication?
            Bacteriophage replication modules.
            Christoph Weigel, Harald Seitz (2005). FEMS Microbiology Reviews 30:321-381.
     
  6. Gene regulation group (Group 2, Fri 3:30 PM: Abdul, Swathi, Sarah, Dustin, Bingjie)
    What proteins do the new phages use to regulate gene expression? Other mycobacteriophage?
    To what DNA sites do these proteins bind?
            Bacteriophage lambda: Alive and well and still doing its thing.
            David I Friedman, Donald L Court (2001). Current Opinion in Microbiology 4:201-207.