October 11, 2018
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1:21:46Now PlayingMIT Computational Biology: Genomes, Networks, Evolution, Health
Prof. Manolis Kellis
Fall 2018
Lecture 10 - Regulatory Genomics
Regulatory genomics: motifs, instances, regions
1. Introduction to regulatory motifs / gene regulation
- Two settings: co-regulated genes (EM,Gibbs), de novo
2. Expectation maximization: Motif matrixpositions
- E step: Estimate motif positions Zij from motif matrix
- M step: Find max-likelihood motif from all positions Zij
3. Gibbs Sampling: Sample from joint (M,Zij) distribution
- Sampling motif positions based on the Z vector
- More likely to find global maximum, easy to implement
4. Evolutionary signatures for de novo motif discovery
- Genome-wide conservation scores, motif extension
- Validation of discovered motifs: functional datasets
5. Evolutionary signatures for instance identification
- Phylogenies, Branch length score Confidence score
6. De novo dissection of regulatory regions in high-resolution
- Massively-parallel reporter assays. Position offset matters.
- 5-bp tiling for high-res dissection: Sharpr-MPRA. Insights
- HiDRA: random ATAC fragmentation + self-reporter assays
Slides for Lecture 10:
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