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Estimation example. Input: Alignment. Model parameters from neutral sequence. Estimation example 2. HMM version. Different gene conservation patterns. Protein Coding Gene. ch10. Known non- coding gene: XIST. chX. RepA. Estimating. - PowerPoint PPT Presentation
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Input:• Alignment.• Model parameters from neutral sequence
Estimation example
Estimation example 2
HMM version
Protein Coding Gene
Known non-coding gene: XIST
ch10
chX
RepA
Different gene conservation patterns
Find a ML estimator for using the EM algorithm.
Score:
Decompose Q by “extracting” the stationary distribution:
π
R: Neutral substitution pattern
: Site specific forcesπ
πEstimating
Unlikeliness Score
Rate Score
Comparison
43% vs 16% detection by vs.
ω π
ωπ
Proof of concept
Gene and gene regulation
GTACTAAGCTACTGTATGGAGGCTHuman
Mouse *****GAGC**********ATGC*
Dog *****AGGT**********CGGC*
Bat *****AGCT**********AGAC*
Find regions in the alignment whose substitution pattern is explained by the motif.
x
x
x
A generalization: Conserved motif discovery
P53
MDM2
Novel non coding gene
M. Huarte, O. Zuk, M. Guttman
P53 Motif instance conservation