| I. MOLECULAR BIOLOGY AND BIOLOGICAL
CHEMISTRY |
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The genetic material |
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Nucleotides |
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Orientation |
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Base pairing |
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The central dogma of molecular biology |
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Gene structure and information content |
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Promoter sequences |
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The genetic code |
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Open reading frames |
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Introns and exons |
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Protein structure and function |
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Primary structure |
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Secondary, tertiary and quaternary structure |
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The nature of chemical bonds |
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Anatomy of an atom |
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Valence |
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Electronegativity |
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Hydrophilicity and hydrophobicity |
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Molecular biology tools |
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Restriction enzymes |
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Gel electrophoresis |
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Blotting, hybridization and microarrays |
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Cloning |
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Polymerase chain reaction (PCR) |
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DNA sequencing |
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Genomic information content |
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C value paradox |
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Reassociation kinetics |
| II. DATA SEARCHES AND PAIRWISE ALIGNMENTS |
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Dot plots |
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Simple alignments |
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Scoring |
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Gaps |
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Simple gap penalties |
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Origination and length penalties |
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Scoring matrices |
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Dynamic programming: The Needleman and
Wunsch algorithm |
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Local and global alignments |
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Global and Semi-global alignments |
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The Smith-Waterman algorithm |
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Database searches |
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BLAST and its relatives |
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Other algorithms |
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Multiple sequence alignments |
| III. SUBSTITUTION PATTERNS |
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Patterns of substitutions within genes |
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Mutation rates |
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Functional constraint |
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Synonymous vs. nonsynonymous changes |
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Indels and psuedogenes |
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Substitutions vs. mutations |
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Fixation |
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Estimating substitution numbers |
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Jukes/Cantor model |
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Transitions and transversions |
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Kimura's two-parameter model |
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Models with even more parameters |
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Substitutions between protein sequences |
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Variations in substitution rates between
genes |
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Molecular clocks |
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Relative rate tests |
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Causes of rate variation in lineages |
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Evolution in organelles |
| IV. DISTANCE-BASED METHODS OF PHYLOGENETICS |
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History of molecular phylogenetics |
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Advantages to molecular phylogenies |
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Phylogenetic trees |
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Terminology of tree reconstruction |
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Rooted and unrooted trees |
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Gene vs. species trees |
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Character and distance data |
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Distance matrix methods |
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UPGMA |
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Estimation of branch lengths |
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Transformed distance method |
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Neighbor's relation method |
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Neighbor-joining methods |
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Maximum likelihood approaches |
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Multiple sequence alignments |
| V. CHARACTER-BASED APPROACHES TO PHYLOGENETICS |
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Parsimony |
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Informative and uninformative sites |
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Unweighted parsimony |
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Weighted parsimony |
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Inferred ancestral sequences |
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Strategies for faster searches |
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Branch and bound |
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Heuristic |
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Consensus trees |
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Tree confidence |
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Bootstrapping |
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Parametric tests |
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Comparison of phylogenetic methods |
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Molecular phylogenies |
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The tree of life |
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Human origins |
| VI. GENOMICS AND GENE RECOGNITION |
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Prokaryotic genomes |
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Prokaryotic gene structure |
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Promoter elements |
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Open reading frames |
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Conceptual translation |
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Termination sequences |
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GC-content |
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Prokaryotic gene density |
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Eukaryotic genomes |
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Eukaryotic gene structure |
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Promoter elements |
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Regulatory protein binding sites |
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Open reading frames |
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Introns and exons |
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Alternative splicing |
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CpG islands |
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GC-content |
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Isochores |
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Codon usage bias |
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Gene expression |
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cDNAs and ESTs |
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Serial analysis of gene expression (SAGE) |
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Microarrays |
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Transposition |
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Repetitive elements |
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Eukaryotic gene density |
| VII. PROTEIN FOLDING |
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Polypeptide composition |
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Amino acids |
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Backbone flexibility, phi and psi |
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Secondary structure |
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Accuracy of predictions |
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Chou-Fasman/GOR method |
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Tertiary and quaternary structure |
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Hydrophobicity |
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Disulfide bonds |
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Active structures vs. most stable structures |
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Protein folding |
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Lattice models |
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Off-lattice models |
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Energy functions and optimization |
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Structure prediction |
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Comparative modeling |
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Threading: Reverse protein folding |
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Predicting RNA secondary structures |
| VIII. PROTEOMICS |
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From genomes to proteomes |
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Protein classification |
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Enzyme nomenclature |
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Families and superfamilies |
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Folds |
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Experimental techniques |
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2D electrophoresis |
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Mass spectrometry |
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Protein microarrays |
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Inhibitors and drug design |
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Ligand screening |
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Docking |
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Database screening |
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X-ray crystal structures |
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Empirical methods and prediction techniques |
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Postranslational modification prediction |
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Protein sorting |
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Proteolytic cleavage |
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Glycosylation |
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Phosporylation and sulfation |
| Appendix 1: A gentle introduction to
programming and data structures |
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Introduction |
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The basics |
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Creating and compiling computer programs |
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Variables and values |
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Data typing |
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Basic operations |
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Program control |
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Statements and blocks |
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Conditional execution |
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Loops |
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Readability |
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Structured programming |
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Comments |
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Descriptive variable names |
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Data structures |
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Arrays |
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Pointers and dynamic memory allocation |
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Strings in PERL |
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Input and output |
| Appendix 2: Enzyme kinetics |
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Enzymes as biological catalysts |
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The Henri-Michaelis-Menten equation |
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Vmax and Km |
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Direct plot |
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Lineweaver-Burk reciprocal plot |
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Eadie-Hofstee plot |
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Simple inhibition systems |
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Competitive inhibition |
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Noncompetitive inhibition |
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Reversible and irreversible inhibition |
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Effects of pH and temperature |
| Appendix 3: Sample programs in PERL
and worksets |
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Conceptual translation |
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Dot matrix |
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Relative rate test |
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UPGMA |
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Common ancestor |
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Splice junction recognition |
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Hydrophobicity calculator |
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DNA binding domains |
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Lineweaver-Burk plot |
