Introduction to Bioinformatics - COIN81
Assignment Four - Biology Workbench and Phylogenetics
There are at least three projects that you can do using Biology Workbench (please refer to the phylogenetics page for step-by-step directions). Each of them involves uploading a set of sequences into Biology Workbench. The directions for setting up an account at biology workbench are as follows. First, go to Biology Workbench at SDSC.
If you have an account set up, then simply enter, if not, then set up a free account, which takes about 30 seconds. Write down your password.
Learning Biology Workbench can be tricky. You might want to download and read How to to Use Biology Workbench before this exercise.
We will do a multiple sequence alignment after uploading the HIV nucleotide and or protein sequences. Do both of these experiments, followed by the Prion evolution comparison. Depending on how that goes, you might decide to do your own study. SARS would be interesting.
HIV mutation study - You will compare sequences from HIV clones taken from IV drug users at 6 month intervals following an initial seropositve diagnosis. These patients were categorized as slow, moderate, or rapid progressors. Read the Markham paper to get a good background. The download this archive to upload into your account in biology workbench. Do a ClustalW and compare patients, then compare diagrams, to the Markham paper.
HIV-SIV HTLV-STLV comparison - This is a comparison of envelope proteins from HIV, SIV, HTLV, and STLV. Download this archive.
Prion evolution comparison - An excellent assignment using the the tutorial above to study Prion proteins. Download this archive.
Deliverables: Create dendrograms (cladograms) for the HIV mutation study, read the Markham paper, and pose your hypothesis about what is going on inside the body during the course of an HIV infection (to AIDS). What are the variables that contribute to the onset of AIDS for rapid progressors, moderate progressors, and non-progressors. Explain the difference between diversity and divergence, and synonymous and non-synonymous mutations. What role does the immune system itself play in the progression of the disease?
I have set up a temporary folder for you to use for these exercises. You can also access a step-by-step for the HIV mutation study here.
HIV-SIV HTLV-STLV comparison - Upload the eight amino acid sequences to Biology workbench. You can do that all in one shot from the sequence files shown on this page. Create dendrograms (cladograms) for the envelop proteins. What are the interesting associations found here? If you have time, investigate the topic of retroviruses, retrotransposons, and retro elements. Comment on the evolution of viruses - what role they might play in ecology, and what value they might have provided in the journey from molecular evolution to single celled organisms.
Prion evolution comparison - This exercise builds on what we did with HIV-SIV-HTLV-STLV. As you did above, upload the protein sequences and perform a ClustalW multiple sequence alignment, and create a dendrogram (cladogram). What relationships did you discover?
SARS - This is tricky. Download and scan the Science articles on sequence and proposed structure of the SARS virus. See also the comments on the deletion of key nucleotides from the Civet Cat. Use these to locate the M, N, and S amino acid sequences from various Coronaviruses. Use the data from SARS genome or compile it from data at NCBI. (This could take you a while, try looking at this file and or this archive). Attempt a dendrogram, and compare it to the Science papers. Could you do this exercises for other viruses and or proteins?
HIV - use Google to find recent literature on where HIV came from. What is your theory?
Avian Flu - See the full exercise at http://www.informaticus.org/workshop/Influenza/Influenza.htm This exercise integrates a significant amount of work related to finding and downloading sequence data.
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