Download CG7b-PSSM

Intro to Probabilistic Models
PSSMs
Computational Genomics,
Lecture 6b
Partially based on slides by Metsada Pasmanik-Chor
Biological Motives
A large number of biological units with common functions
tend to exhibit similarities at the sequence level. These
include very short “motives”, such as
gene splice sites, DNA regulatory binding sites, recognized
by transcription factors (proteins that bind to the promoter
and control gene expression), microRNAs, and all the way
to protein families.
Often it is desirable to model such motives, to enable
searching for new ones. Probabilistic models are very
useful. Today we deal with PSSM - the simplest.
Promoter…
Regulation of Genes
Transcription Factor
(Protein)
RNA polymerase
(Protein)
DNA
Regulatory Element
www.cs.washington.edu/homes/tompa/papers/binding.ppt
Gene
Regulation of Genes
Transcription Factor
(Protein)
RNA polymerase
DNA
Regulatory Element
Gene
Regulation of Genes
New protein
RNA
polymerase
Transcription Factor
DNA
Regulatory Element
Gene
Motif Logo
• Motifs can mutate on
less important bases.
Position: 1234567
• The five motifs at top
right have mutations in
position 3 and 5.
• Representations called
motif logos illustrate
the conserved regions
of a motif.
http://weblogo.berkeley.edu
http://fold.stanford.edu/eblocks/acsearch.html
TGGGGGA
TGAGAGA
TGGGGGA
TGAGAGA
TGAGGGA
Example: Calmodulin-Binding Motif
(calcium-binding proteins)
PSSM Starting Point
•
A gap-less MSA of known instances of a
given motif. Representing the motif by either:
1. Consensus.
2. Position Specific Scoring Matrix (PSSM).
Consider now a specific “motives server”,
called Consite.
Sequence logos: Visualizing PSSMs
Sequence logos: Visualizing PSSMs (2)