journal club 06/27/08
DESCRIPTION
Journal club 06/27/08. Phylogenetic footprinting. A technique used to identify TFBS within a non-coding region of DNA of interest by comparing it to the orthologous sequences in different species (1988 by Tagle) - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/1.jpg)
Journal club06/27/08
![Page 2: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/2.jpg)
Phylogenetic footprinting
• A technique used to identify TFBS within a non-coding region of DNA of interest by comparing it to the orthologous sequences in different species (1988 by Tagle)
• The function and DNA binding preferences of transcription factors are well-conserved between diverse species
• Important non-coding DNA sequences that are essential for regulating gene expression will show differential selective pressure. (A slower rate of change occurs in TFBS than in other parts of the non-coding genome)
![Page 3: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/3.jpg)
Phylogenetic footprinting
![Page 4: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/4.jpg)
Phylogenetic footprinting
• Not all conserved sequences are under selection pressure
• To eliminate false positives, statistical analysis must be performed that the motifs reported have a mutation rate meaningfully less than that of the surrounding nonfunctional sequence.
![Page 5: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/5.jpg)
Mixture selective pressure
• Maintain the function of the protein encoded by the gene (AA selecvtive pressure)
• Maintain their regulatory role (CRUNCS) – ex: regulatory factors binding sites
![Page 6: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/6.jpg)
Methods
• Sequence conservation:
1. Entropy score
2. Parsimony score
• Conservation p-value (mixture models)
• Posterior distributions of conservation scores
• Conditional p-values
![Page 7: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/7.jpg)
Parsimony V.S. Entropy Score
![Page 8: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/8.jpg)
Fitch’s algorithm
![Page 9: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/9.jpg)
Aligned codons illustrating to what extent the conservation of each column is surprising, given the amino acids encoded
L: CUN, UUA, UUG; W: UUG; V: GUN; A:GCN; G:GGN; D: GAU, GAC
How surprising?1. Conditional model
![Page 10: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/10.jpg)
1. Conditional model
![Page 11: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/11.jpg)
2. Mixture model
Hydrophobic favorGlycine favor
50 functional classes
![Page 12: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/12.jpg)
2. Mixture model
![Page 13: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/13.jpg)
Non-coding model: HKY model
j ( A , j ,C , j ,G, j ,T , j )
j represents the transition/transversion rate ratio for
j
![Page 14: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/14.jpg)
How to compute :
![Page 15: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/15.jpg)
![Page 16: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/16.jpg)
![Page 17: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/17.jpg)
![Page 18: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/18.jpg)
![Page 19: Journal club 06/27/08](https://reader035.vdocuments.us/reader035/viewer/2022062520/568158ce550346895dc61906/html5/thumbnails/19.jpg)