Assignment 8, due Wednesday Mar. 17
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 & tree of life; 'artificial life';
- Lecture 2: Mutations as molecular basis for evolutionary change. CpG mutations/CpG islands. Segmental changes. Mutation fates. Neutral/nearly neutral theories.
- Lecture 3: Mutation & substitution rates. Overview of goals & experimental approaches of molecular biology; role of sequence analysis. Generalities on algorithms for biological data; directed graphs. Reading: Durbin et al. section 2.1, 2.2, 2.3.
- Lecture 4: Depth structure of directed acyclic graphs (DAGs); trees and linked lists. Dynamic programming on weighted DAGs. Algorithmic complexity. Reading: Durbin et al. 2.4, 2.5, 2.6.
- Lecture 5: Maximal-scoring sequence segments. Edit graphs & sequence alignment. Smith-Waterman algorithm. Needleman-Wunsch algorithm. Reading: Durbin et al. 6.1, 6.2, 6.3; Ewens & Grant 1.1, 1.2, 1.12
- Lecture 6: Local vs. global. Multiple sequence alignment; edge weight issues. Linear space algorithms. Reading: Ewens & Grant 3.1, 3.2, 3.4, 3.6, 5.2, 9.1, 9.2
- Lecture 7: Linear space algorithms (cont'd). General & affine gap penalties. Profiles.Smith-Waterman special cases, self-similarity. Speedups based on nucleating word matches: BLAST, FASTA, cross_match. Reading: Ewens & Grant 5.3.1, 5.3.2, 12.1, 12.2, 12.3; Durbin et al. chapter 3
- Lecture 8: Speedups based on nucleating word matches: BLAST, FASTA, cross_match (cont'd). 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. Comparing alternative models. Reading: Ewens & Grant 12.2, 12.3; Durbin et al. chapter 3
- Lecture 9: Weight matrices for site models. weight matrices for splice sites in C. elegans. Score distributions. Limitations of site models (variable spacing, non-independence).Hidden Markov Models: introduction; formal definition; HMM examples: -- splice sites.
- Lecture 10: HMM examples: 2-state models, 7-state prokaryote genome model: Probabilities of sequences; computing HMM probabilities via associated WDAG. Reading: Ewens & Grant 1.14, Appendix B.10.
- Lecture 11: HMM Parameter estimation: Viterbi training, Baum-Welch (EM) algorithm; specialized techniques. Multiple alignment via profile HMMs. Information theory: Entropy. Information inequality.
- Lecture 12: Boltzmann distribution, Coding theory/data compression, uniquely decodable codes. Kraft inequality, entropy & expected code length. Information; relative entropy. Relative entropies of site models.
- Lecture 13: Sequence logos. Random variables; exact probability distribution for weight matrix scores. Non-independence in background & compositional models. Reading: Ewens & Grant 5.3.4
- Lecture 14: Probability models of biological sequences, allowing dependencies. Order k Markov models; minimum description length principle; overfitting. Sparse probabilistic suffix trees.
- Lecture 15: Sparse probabilistic suffix trees (cont'd). Gene identification in eukaryotes. Reading: Ewens & Grant chapter 7
- Lecture 16: Gene identification in eukaryotes (cont'd).
- Lecture 17: Gene identification in eukaryotes (cont'd). Detection of evolutionarily conserved regions using Phylo-HMMs. Reading: Siepel et al.
- Lecture 18: Detection of evolutionarily conserved regions using Phylo-HMMs (cont'd).
- Lecture 19: Phylo-HMMs (cont'd). Maximal scoring segments. D-segments, exact probability dist'ns for segment scores.
OTHER RELEVANT COURSES AT UW:
COMPUTATIONAL BIOLOGY COURSES AT OTHER SITES:
- Computational Molecular Biology (Washington University)
- Computational Genomics (Ron Shamir, Tel Aviv University)
- Computational Molecular Biology (Doug Brutlag & Lee Kozar, Stanford)
- Computational Genomics (Doug Brutlag, Stanford)
- Representations and Algorithms for Computational Molecular Biology (Russ Altman, Stanford)
- Computational Biology: Genomes, Networks, Evolution (James E. Galagan and Manolis Kellis, MIT)
- Computational Genomics (Adam Siepel, Cornell)
- Computational Biology (Robert Murphy, Carnegie Mellon)
- Introduction to Computational Biology (Steven Skiena, Stony Brook)