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Systems Biology is changing the way biology is done. Is it a fad or is it effective? This blog tracks current happenings and helps you stay on top of the field. You can find a list of relevant papers at systems biology paper watch Have you heard a talk or read a paper in bioinformatics / systems biology you would like to tell other people about? Email: and get the word out!

Sunday, December 04, 2005

Manolis Kellis, MIT
"Regulatory network discovery and evolution"
First part of the talk was comparative genomics techniques for short regulatory motifs. Since motifs are small ~8bp and degenerate this is hard without comparative techniques.
Genome wide motif discovery by looking for over represented n-mers. They did an apparently simple counting technique that seemed to work well.
Promoter motifs are symmetrically conserved in both forward and reverse strand. This is not true for 3'-UTR motifs (which is coordinate with their role in post transcriptional modification.
3-UTr are usually ~8 long and end in A which alludes to miRNA them being miRNA targets. Scanning the miRNA database confirms this.

went back and looked for miRNAs that are complements for the 3-utrs they find. They select for those that form stem loops, in total they find 258 candidates of which 114 confirm known miRNA genes. Estimate that 20% of human genes are targeted by miRNA.

Use full genome duplication as a model for network evolution using motif based networks. Duplication in yeasts (K. waltii and cerevisiae) , pufferfish and even human (plos 2005).
Duplicated genes show accelerated divergence and that in 95% of theses cases on copy evolves faster than the other.
Using a simple scheme for modeling interactions gain/loss they can model the motifs of interactions in duplicated genes.
Noted that paralogs are more likely to interact with each other. This may be due to proximity or redundancy.


Anonymous mary said...

Can somebody clarify why he was happy with the results for experimental verification of the miRNAs/miRNA target predictions? One of the few stats about this was 6 verified out of 12 tested... can't remember the details.

4:04 PM  
Anonymous mary said...

This comment has been removed by a blog administrator.

4:46 PM  
Anonymous Anonymous said...

i think he said that 6 out of 12 were known miRNA targets published in literature.

11:53 PM  
Blogger Mike Lin said...

The experimental verification was a PCR amplification of the "transcript" of 12 miRNA genes, not a knockdown of their putative targets. We have no idea whether these miRNA genes are expressed only in certain tissues, only during development, etc. Nonetheless, in the pooled RNA of 10 tissues, 6 out of the 12 were clearly expressed.

Of 242 candidate miRNA genes that Xiaohui discovered, 113 corresponded to known miRNA genes, and 129 are novel.

I wasn't involved in this study directly but these are both facts that I gleaned directly from the Nature paper.

11:24 AM  
Blogger Francis Crick said...

Thank you very much, Mike Lin.

3:43 PM  

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