Lessons from DNA Microarrays


1) Unknown Genes

2) Vaccine Evolution

3) Clustered Image Map


Unknown Genes - "guilt by association"

Can we use DNA microarrays to predict cellular roles for "unknown genes"?

Guilt by association means if 3 out of four genes are known and the unknown one appears to be coordinately regulated, then perhaps the unknown gene has a related function.

 

Two examples from DeRisi et al. diauxic shift paper:

Seven Repressed Genes

Seven Induced Genes

 


Vaccine Evolution

Why has the TB vaccine gotten less effective over time?
Vaccine was derived from M. bovis strain.

Experimental Design:

Subset of Microarray

 

Have the vaccine genomes changed over time?

16 Regions of Deletion (RD) Identified

 

Which strains would you use?

Dendrogram of TB Vaccine Evolution

 


Clustered Image Map: Interactive Database for Cancer Treatment

1) You will have to register (free) here. You will need your user name and password from your registration before you can go to the next step.

2) Once you have your account, go to the CIM site. Take the default settings and click on the green "Create Image" button. It will take a few minutes to return the CIM. We will come back to this. Leave the CIM window open so we can come back to it later.

Do cancer types cluster together?

NCI60 Cell Lines Clustered by DNA Microarray Data

 

Can "signature genes" reveal source of cancers?

 

Can we integrate databases to predict the best treatment for a particular patient?
(individualized medication)

 

3) The CIM you produced compared 118 drugs (X-axis) with NCI60 cell types (Y-axis). In the CIM you produced online, find the cell line RE:CAKI-1 on the Y-axis (scroll in the left frame). Click on the area where you think a drug would work well on RE:CAKI-1. As you click, the image will zoom in. Find a particular drug that works well on RE:CAKI-1.

4) Imagine you had a malignant tumor whose expression profile matched RE:CAKI-1. Go to this page to discover the original source of your cancer.

5) Imagine you had a liver tumor that had a gene expression profile that clustered between cell lines LE:SR and LE:HL-60. What drug would you prescribe to treat the liver tumor?

6) What did you learn in numbers 4 and 5 that you could turn into a research question to further cancer therapy?


ACS Workshop

Genomics Course

Biology Department


Send comments, questions, and suggestions to: macampbell@davidson.edu or (704) 894 - 2692
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