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Questions?

Questions?. Novel ncRNAs are abundant: Ex: miRNAs. miRNAs were the second major story in 2001 (after the genome). Subsequently, many other non-coding genes have been found . Scientific American, 2006. Bacterial Riboswitches. -Breaker Lab. ncRNA gene finding. The RNA world hypothesis:

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Questions?

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  1. Questions?

  2. Novel ncRNAs are abundant: Ex: miRNAs • miRNAs were the second major story in 2001 (after the genome). • Subsequently, many other non-coding genes have been found

  3. Scientific American, 2006

  4. Bacterial Riboswitches • -Breaker Lab

  5. ncRNA gene finding • The RNA world hypothesis: • RNA are as important as protein coding genes. • Many undiscovered ncRNA exist • Computational methods for discovering ncRNA are not mature. • What are the clues to non-coding genes? • Structure: Given a sequence, what is the structure into which it can fold with minimum energy?

  6. RNA structure: Basics • Key: RNA is single-stranded. Think of a string over 4 letters, AC,G, and U. • The complementary bases form pairs. • A <-> U, C <-> G, G <-> U • Base-pairing defines a secondary structure. The base-pairing is usually non-crossing.

  7. RNA structure: Basics • Key: RNA is single-stranded. Think of a string over 4 letters, AC,G, and U. • The complementary bases form pairs. • Base-pairing defines a secondary structure. The base-pairing is usually non-crossing.

  8. RNA structure: pseudoknots • Sometimes, unpaired bases in loops form ‘crossing pairs’. These are pseudoknots.

  9. De novo RNA structure prediction • Any set of non-crossing base-pairs defines a secondary structure. • Abstract Question: • Given an RNA string find a structure that maximizes the number of non-crossing base-pairs • Incorporate the true energetics of folding • Incorporate Pseudo-knots

  10. ncRNA discovery • Q: Given genomic DNA, discover all regions likely to be ncRNA • ncRNA (unlike other DNA) should have secondary structure • Possible Approach: • Find all substrings that fold into a low energy structure.

  11. Unfortunately… • Random DNA (with high GC content) often folds into low-energy structures. • What other signals determine non-coding genes?

  12. Discovering ncRNA: Approach 2 • Consider each ncRNA family separately. Compute features that are distinct from other sequences. • Many families are of particular interest • miRNA • Riboswitches

  13. ncRNA: miRNA • ncRNA ~22 nt in length • Pairs to sites within the 3’ UTR, specifying translational repression. • Similar to siRNA (involved in RNAi) • Unlike siRNA, miRNA do not need perfect base complementarity • Until recently, no computational techniques to predict miRNA • Most predictions based on cloning small RNAs from size fractionated samples -Burge Lab

  14. Comparative approach to discovering ncRNA • Given a pair of conserved sequences, are they conserved because they encode ncRNA? • Q: How would you compute such conserved pairs in the first place?

  15. Comparative Approach to discovering ncRNA • Given a query ncRNA (sequence & structure), compute all homologs that are similar in sequence and structure. • How can you do it efficiently? query db sequence • We will answer these questions

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