Table of Contents
I. MOLECULAR BIOLOGY AND BIOLOGICAL CHEMISTRY.
The genetic material.
Nucleotides.Orientation.Base pairing.The central dogma of molecular
biology.
Gene structure and information content.
Promoter sequences.The genetic code.Open reading frames.Introns and
exons.
Protein structure and function.
Primary structure.Secondary, tertiary and quaternary
structure.
The nature of chemical bonds.
Anatomy of an atom.Valence.Electronegativity.Hydrophilicity and
hydrophobicity.
Molecular biology tools.
Restriction enzymes.Gel electrophoresis.Blotting, hybridization and
microarrays.Cloning.Polymerase chain reaction (PCR).DNA
sequencing.
Genomic information content.
C value paradox.Reassociation kinetics.
II. DATA SEARCHES AND PAIRWISE ALIGNMENTS.
Dot plots.
Simple alignments.
Scoring.
Gaps.
Simple gap penalties.Origination and length penalties.
Scoring
matrices.
Dynamic programming: The Needleman and Wunsch algorithm.
Local and global alignments.
Global and Semi-global alignments.The Smith-Waterman
algorithm.
Database searches.
BLAST and its relatives.Other algorithms.
Multiple sequence
alignments.
III. SUBSTITUTION PATTERNS.
Patterns of substitutions within genes.
Mutation rates.Functional constraint.Synonymous vs. nonsynonymous
changes.Indels and psuedogenes.Substitutions vs.
mutations.Fixation.
Estimating substitution numbers.
Jukes/Cantor model.Transitions and transversions.Kimura's
two-parameter model.Models with even more parameters.Substitutions
between protein sequences.
Variations in substitution rates
between genes.
Molecular clocks.
Relative rate tests.Causes of rate variation in
lineages.
Evolution in organelles.
IV. DISTANCE-BASED METHODS OF PHYLOGENETICS.
History of molecular phylogenetics.
Advantages to molecular phylogenies.
Phylogenetic trees.
Terminology of tree reconstruction.Rooted and unrooted trees.Gene
vs. species trees.Character and distance data.
Distance matrix
methods.
UPGMA.Estimation of branch lengths.Transformed distance
method.Neighbor's relation method.Neighbor-joining
methods.
Maximum likelihood approaches.
Multiple sequence alignments.
V. CHARACTER-BASED APPROACHES TO PHYLOGENETICS.
Parsimony.
Informative and uninformative sites.Unweighted parsimony.Weighted
parsimony.
Inferred ancestral sequences.
Strategies for faster searches.
Branch and bound.Heuristic.
Consensus trees.
Tree confidence.
Bootstrapping.Parametric tests.
Comparison of phylogenetic
methods.
Molecular phylogenies.
The tree of life.Human origins.
VI. GENOMICS AND GENE RECOGNITION.
Prokaryotic genomes.
Prokaryotic gene structure.
Promoter elements.Open reading frames.Conceptual
translation.Termination sequences.
GC-content.
Prokaryotic gene density.
Eukaryotic genomes.
Eukaryotic gene structure.
Promoter elements.Regulatory protein binding sites.
Open reading
frames.
Introns and exons.Alternative splicing.CpG
islands.
GC-content.
Isochores.Codon usage bias.
Gene expression.
cDNAs and ESTs.Serial analysis of gene expression
(SAGE).Microarrays.
Transposition.
Repetitive elements.
Eukaryotic gene density.
VII. PROTEIN FOLDING.
Polypeptide composition.
Amino acids.Backbone flexibility, phi and psi.
Secondary
structure.
Accuracy of predictions.Chou-Fasman/GOR method.
Tertiary and
quaternary structure.
Hydrophobicity.Disulfide bonds.Active structures vs. most stable
structures.
Protein folding.
Lattice models.Off-lattice models.Energy functions and
optimization.
Structure prediction.
Comparative modeling.Threading: Reverse protein
folding.
Predicting RNA secondary structures.
VIII. PROTEOMICS.
From genomes to proteomes.
Protein classification.
Enzyme nomenclature.Families and
superfamilies.Folds.
Experimental techniques.
2D electrophoresis.Mass spectrometry.Protein
microarrays.
Inhibitors and drug design.
Ligand screening.
Docking.Database screening.
X-ray crystal structures.
Empirical methods and prediction techniques.
Postranslational modification prediction.
Protein sorting.Proteolytic cleavage.Glycosylation.Phosporylation
and sulfation.
Appendix 1: A gentle introduction to programming and data
structures.
Introduction.
The basics.
Creating and compiling computer programs.Variables and values.Data
typing.Basic operations.
Program control.
Statements and blocks.Conditional
execution.Loops.
Readability.
Structured programming.Comments.Descriptive variable names.
Data
structures.
Arrays.Pointers and dynamic memory allocation.Strings in
PERL.
Input and output.
Appendix 2: Enzyme kinetics.
Enzymes as biological catalysts.
The Henri-Michaelis-Menten equation.
Vmax and Km.Direct plot.Lineweaver-Burk reciprocal
plot.Eadie-Hofstee plot.
Simple inhibition systems.
Competitive inhibition.Noncompetitive inhibition.Reversible and
irreversible inhibition.Effects of pH and temperature.
Appendix 3: Sample programs in PERL and worksets.
Conceptual translation.
Dot matrix.
Relative rate test.
UPGMA.
Common ancestor.
Splice junction recognition.
Hydrophobicity calculator.
DNA binding domains.
Lineweaver-Burk plot.Promotional Information
Fundamental Concepts of Bioinformatics is the first book
co-authored by a biologist and computer scientist that is
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available for analyzing data, how to understand the basic
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the major concepts without overwhelming readers. Problems at the
end of each chapter use real data to help readers apply what they
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