Why predict RNA?

DNA

PROTEIN

RNA

mRNAtRNA

rRNA

Protein Biosynthesis Regulation

Noncoding RNA

cis- or trans-regulatory

trans-regulatory

Antisense RNA

Riboswitches

CRISPR

etc.

Traditional paradigm

Regulatory sRNA

Hypothesis:

Virulence in N. Meningitiditis is associated with regulation of virulence genes

sRNA Challenges

• less information– small – sequence-acting

• misleading information– dual purpose

• boundaries not obvious

Methods to predict coding, tRNA and rRNA genes are much more mature than those for sRNA.

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

Profile HMM

• <Krogh figure>

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

What is Covariance?

• <MSA figure explaining covariance>

• <secondary sequence explaining covariance-structure relationship>

Covariance Model

• Extends Profile HMM to include basepairing information

• <Figure>

Noncomparative Prediction

• Transcription signals– <List types>– <Extend figure to include signals>– <Include binding example>

• Limited utility because of …

Software

Noncomparative MethodsList Comparative Methods

Combined: may have relevance for predicting virulence