Why predict RNA?

1. DNA cis- or trans-regulatory trans-regulatory Antisense RNA Riboswitches CRISPR etc. RNA rRNA mRNA tRNA PROTEIN Why predict RNA? Regulation Protein Biosynthesis Noncoding RNA Traditional paradigm

2. Regulatory sRNA Hypothesis: Virulence in N. Meningitiditis is associated with regulation of virulence genes

3. sRNA Challenges Methods to predict coding, tRNA and rRNA genes are much more mature than those for sRNA. • less information • small • sequence-acting • misleading information • dual purpose • boundaries not obvious

4. Fundamental Methodology • Comparative • Analogous to protein comparative models • Scoring is tailored for RNA • Sequence-based weight matrices (RFAM) • Profile HMM • Structure-enhanced (Covariance Model) • Noncomparative • Search for transcriptional signals

5. Profile HMM • <Krogh figure>

6. RFAM • RNA database • Each RNA sequence classified in a Family • Families determined by Covariance Model (CM) • CM extends Profile HMM to include Covariance • Annotation of Families with Wikipedia

7. What is Covariance? • <MSA figure explaining covariance> • <secondary sequence explaining covariance-structure relationship>

8. Covariance Model • Extends Profile HMM to include basepairing information • <Figure>

9. Noncomparative Prediction • Transcription signals • <List types> • <Extend figure to include signals> • <Include binding example> • Limited utility because of …

10. Software Combined: may have relevance for predicting virulence