Difference between revisions of "CSB Assignment Week 4"

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==Exercises==
 
==Exercises==
  
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January 30 2014 saw the publication of what may be the most important scientific advance published in our lifetimes. In two ''nature'' papers, Haruko Obokata described the creation of so-called '''STAP''' (stimulus-triggered acquisition of pluripotency) cells. These cells can be generated by simple stress-protocols applied to leukocytes, but also to brain-, skin-, muscle-, fat-, bone marrow, lung- and liver-derived cells. Successful protocols include bathing the cells in moderately acidic medium for half an hour, mechanically perturbing the cells, or inducing plasma cell membrane pores with streptolysin. Post stress, cells shrink, stop proliferating, downregulate their differentiation gene markers and begin expressing markers of pluripotent stem cells that include our friends OCT4, Nanog, and Sox-2, and others. Cell clusters that form after this apparent transformation can be propagated. '''Strikingly, not only are these clusters able to grow into entire embryos after blastocyst injection, and further into normal, adult mice, but these mice are fertile and demonstrate germline transmission of their genetic markers into their offspring.'''
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{{Task|1=
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'''1.''' Read ...
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:{{#pmid: 24476887}}
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:Among the obvious questions one has to ask are: can these mouse-findings be transferred to humans, what are the upstream signals that trigger the pluripotency response, and can this network be controlled? Obokata ''et al.'' describe the transformation as the release of an epigenetic differentiation state and this may point into the direction of genes that could possibly be involved.
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:How would you find them?
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'''2.''' Think about what datasets you might need to pursue these questions and what comparisons you might want to undertake.
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'''3.''' Navigate to [http://www.ncbi.nlm.nih.gov/gds '''GEO'''] and search whether such datasets are available. Note down any that you find and '''bring your list to class'''.
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==Pre-reading==
 
==Pre-reading==

Revision as of 03:12, 3 February 2014

Assignments for Week 4


Note! This assignment is currently inactive. Major and minor unannounced changes may be made at any time.

 
 


Exercises for this week relate to this week's lecture.
Pre-reading for this week will prepare next week's lecture.
Exercises and pre-reading will be topics on next week's quiz.



Exercises

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Task:

  • Work through the DAVID tutorial published in nature protocols:
Huang et al. (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44-57. (pmid: 19131956)

PubMed ] [ DOI ]

  • Access the Web version of the article, it conveniently contains the required links.
  • Use Demo List 2, provided on the DAVID site for your analysis. Remember to read the description of the gene list.
  • Do not use any of the Java tools. As of this writing Java applets in Web browsers are considered fundamentally insecure; Java should be disabled in your browser.
  • For each of the analysis steps, think clearly about whether the results support od contradict your expectations about the data. Feel free to discuss your expectations and findings on the mailing list.
  • If there are any problems with the assignment, contact me!

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January 30 2014 saw the publication of what may be the most important scientific advance published in our lifetimes. In two nature papers, Haruko Obokata described the creation of so-called STAP (stimulus-triggered acquisition of pluripotency) cells. These cells can be generated by simple stress-protocols applied to leukocytes, but also to brain-, skin-, muscle-, fat-, bone marrow, lung- and liver-derived cells. Successful protocols include bathing the cells in moderately acidic medium for half an hour, mechanically perturbing the cells, or inducing plasma cell membrane pores with streptolysin. Post stress, cells shrink, stop proliferating, downregulate their differentiation gene markers and begin expressing markers of pluripotent stem cells that include our friends OCT4, Nanog, and Sox-2, and others. Cell clusters that form after this apparent transformation can be propagated. Strikingly, not only are these clusters able to grow into entire embryos after blastocyst injection, and further into normal, adult mice, but these mice are fertile and demonstrate germline transmission of their genetic markers into their offspring.

Task:
1. Read ...

Obokata et al. (2014) Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature 505:641-7. (pmid: 24476887)

PubMed ] [ DOI ]

Among the obvious questions one has to ask are: can these mouse-findings be transferred to humans, what are the upstream signals that trigger the pluripotency response, and can this network be controlled? Obokata et al. describe the transformation as the release of an epigenetic differentiation state and this may point into the direction of genes that could possibly be involved.
How would you find them?

2. Think about what datasets you might need to pursue these questions and what comparisons you might want to undertake.

3. Navigate to GEO and search whether such datasets are available. Note down any that you find and bring your list to class.

Pre-reading

The Encode project is a current paradigm for the integration of multiple -omics datasets for comprehensive annotation of the human genome.

ENCODE Project Consortium (2011) A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol 9:e1001046. (pmid: 21526222)

PubMed ] [ DOI ]


State-of-the-art proteome analysis. In your reading, make sure you understand the experimental principles applied, but focus on the computational techniques.

Beck et al. (2011) The quantitative proteome of a human cell line. Mol Syst Biol 7:549. (pmid: 22068332)

PubMed ] [ DOI ]