Assignment 8, due Sunday Mar. 11
SYLLABUS & LECTURE SLIDES:
Math Notation
Nature paper on Avida ( Avida web site )
Nature paper on human genome sequence
Nature paper on mouse genome sequence
Rabiner tutorial on HMMs
HMM scaling tutorial (Tobias Mann)
- Biological Review (1st discussion section): 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.
- 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 theory, mutation & substitution rates.
- Lecture 3: 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.
- Lecture 4: Maximal-scoring sequence segments; edit graphs & sequence alignment. Reading: Durbin et al. section 2.1, 2.2, 2.3.
- Lecture 5: Smith-Waterman algorithm, Needleman-Wunsch algorithm. Local vs. global. Profiles; edge weight issues; linear space algorithms. General & affine gap penalties. Profiles. Reading: Durbin et al. 2.4, 2.5, 2.6.
- Lecture 6: Hidden state DAGs; Smith-Waterman special cases, self-similarity.
Speedups based on nucleating word matches: BLAST, FASTA, cross_match. Multiple sequence alignment. Probability models on sequences;; review of basic probability theory: probability spaces, conditional probabilities, independence. Reading: Durbin et al. 6.1, 6.2, 6.3; Ewens & Grant 1.1, 1.2, 1.12
- Lecture 7: Failure of equal frequency assumption for DNA, and for proteins. Site models; examples: 3' splice sites, 5' splice sites, protein motifs; limitations of site models (variable spacing, non-independence) -- splice site illustrations; site probability models. Comparing alternative models, hypothesis tests, likelihood ratio tests. Neyman-Pearson Lemma Reading: Ewens & Grant 3.1, 3.2, 3.4, 3.6, 5.2, 9.1, 9.2
- Lecture 8: Site probability models. Comparing alternative models, hypothesis tests, likelihood ratio tests. Neyman-Pearson Lemma. Weight matrices for site models. weight matrices for splice sites in C. elegans, score distributions. Hidden Markov Models: introduction; formal definition; Reading: Ewens & Grant 5.3.1, 5.3.2, 12.1, 12.2, 12.3; Durbin et al. chapter 3
- Lecture 9: HMM examples: 2-state models, 7-state prokaryote genome model. Probabilities of sequences; computing HMM probabilities via associated WDAG. Reading: Ewens & Grant 12.2, 12.3; Durbin et al. chapter 3
- Lecture 10: HMM Parameter estimation: Viterbi training, Baum-Welch (EM) algorithm; specialized techniques. Multiple alignment via profile HMMs.
- Lecture 11: Information theory: entropy, coding theory/data compression, uniquely decodable codes. Information inequality, Boltzmann distribution, Kraft inequality, entropy & expected code length. Information; relative entropy. Reading: Ewens & Grant 1.14, Appendix B.10.
- Lecture 12: Relative entropies of site models. Sequence logos. Random variables; exact probability distribution for weight matrix scores. 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: exact probability distribution for weight matrix scores. Non-independence in background & compositional models. Probability models of biological sequences, allowing dependencies. Order k Markov models; minimum description length principle; overfitting.
- Lecture 14: Sparse probabilistic suffix trees. Gene identification in eukaryotes. Reading: Ewens & Grant 5.3.4
- Lecture 15: Gene identification in eukaryotes (cont'd).
- Lecture 16: Gene identification in eukaryotes (cont'd). Maximal scoring segments; D-segments; exact probability dist'ns for segment scores. Karlin-Altschul theory for high-scoring segments. Reading: Ewens & Grant chapter 7
- Lecture 17: Karlin-Altschul theory (cont'd).
- Lecture 18: Karlin-Altschul theory (cont'd). 'Non-random' mutations; transcription-coupled asymmetry. paper describing this work.
- Lecture 19: Transcription-coupled asymmetry (cont'd).
OTHER RELEVANT COURSES AT UW:
COMPUTATIONAL BIOLOGY COURSES AT OTHER SITES: