Assignment 8, due Sunday Mar. 15
SYLLABUS & LECTURE SLIDES:
Math Notation
Nature paper on Avida ( Avida web site )
Nature paper on human genome sequence
Nature paper on mouse genome sequence
Siepel et al. paper on PhyloHMMs & sequence conservation
Rabiner tutorial on HMMs
HMM scaling tutorial (Tobias Mann)
- Biological Review : Gene and genome structure in prokaryotes and eukaryotes; the genetic code & codon usage; "global" genome organization. Sources and characteristics of sequence data; Genbank and other sequence databases.
- Programming Review (1st discussion section)
- Lecture 1: Finding exact matches in sequences. Living organisms as imperfect replication machines; theory of evolution.
- Lecture 2: Theory of evolution & tree of life; 'artificial life'. Mutations as molecular basis for evolutionary change. CpG mutations/CpG islands.
- Lecture 3: Segmental changes. Mutation fates. Neutral theory, mutation & substitution rates.
- Lecture 4: Overview of goals & experimental approaches of molecular biology; role of sequence analysis. Generalities on algorithms for biological data; directed graphs; depth structure of directed acyclic graphs (DAGs); trees and linked lists. Dynamic programming on weighted DAGs. Reading: Durbin et al. section 2.1, 2.2, 2.3.
- Lecture 5: Dynamic programming on weighted DAGs; algorithmic complexity; maximal-scoring sequence segments Reading: Durbin et al. 2.4, 2.5, 2.6.
- Lecture 6: Edit graphs & sequence alignment. Smith-Waterman algorithm. Needleman-Wunsch algorithm. Local vs. global. Multiple sequence alignment; edge weight issues. Reading: Durbin et al. 6.1, 6.2, 6.3; Ewens & Grant 1.1, 1.2, 1.12
- Lecture 7: Linear space algorithms. General & affine gap penalties. Profiles. Reading: Ewens & Grant 3.1, 3.2, 3.4, 3.6, 5.2, 9.1, 9.2
- Lecture 8: Smith-Waterman special cases, self-similarity. Speedups based on nucleating word matches: BLAST, FASTA, cross_match. Probability models on sequences; review of basic probability theory: probability spaces, conditional probabilities, independence. Comparing alternative models. Failure of equal frequency assumption for DNA. Site models; examples: 3' splice sites, 5' splice sites, protein motifs. Site probability models. Reading: Ewens & Grant 5.3.1, 5.3.2, 12.1, 12.2, 12.3; Durbin et al. chapter 3
- Lecture 9: Comparing alternative models, Weight matrices for site models. weight matrices for splice sites in C. elegans. Score distributions. Limitations of site models (variable spacing, non-independence). Reading: Ewens & Grant 12.2, 12.3; Durbin et al. chapter 3
- Lecture 10: Hidden Markov Models: introduction; formal definition; HMM examples: -- splice sites; 2-state models, 7-state prokaryote genome model.
- Lecture 11: Probabilities of sequences; computing HMM probabilities via associated WDAG. HMM Parameter estimation: Viterbi training, Baum-Welch (EM) algorithm; specialized techniques. Multiple alignment via profile HMMs. Information theory: entropy, coding theory/data compression, uniquely decodable codes. Information inequality, Boltzmann distribution, Reading: Ewens & Grant 1.14, Appendix B.10.
- Lecture 12: Multiple alignment via profile HMMs. Information theory: entropy, coding theory/data compression, uniquely decodable codes. Information inequality, Boltzmann distribution, Reading: Ewens & Grant 1.3.1, 1.3.2, 1.3.4, 1.4, 1.5, 2.10.1, 4.5, 4.6, 5.2, 5.3.3.
- Lecture 13: Kraft inequality, entropy & expected code length. Information; relative entropy. Relative entropies of site models. Sequence logos.
- Lecture 14: Random variables; exact probability distribution for weight matrix scores. Non-independence in background & compositional models. Probability models of biological sequences, allowing dependencies. Reading: Ewens & Grant 5.3.4
- Lecture 15: Order k Markov models. Order k Markov models; minimum description length principle; overfitting. Sparse probabilistic suffix trees.
- Lecture 16: Gene identification in eukaryotes. Reading: Ewens & Grant chapter 7
- Lecture 17: Gene identification in eukaryotes (cont'd).
- Lecture 18: Detection of evolutionarily conserved regions using Phylo-HMMs. Reading: Siepel et al.
- Lecture 19: Detection of evolutionarily conserved regions using Phylo-HMMs (cont'd). Maximal scoring segments.
- Lecture 20: D-segments; exact probability dist'ns for segment scores. Karlin-Altschul theory for high-scoring segments.
OTHER RELEVANT COURSES AT UW:
COMPUTATIONAL BIOLOGY COURSES AT OTHER SITES: