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| Introduction | |
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| Reading and Writing | |
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| Design and Scope of This Book | |
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| Sequences in Space | |
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| Sequences in Time | |
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| Sequences in Space | |
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| Optimal Pairwise Alignment | |
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| What Is an Alignment? | |
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| Biological Interpretation of the Alignment Problem | |
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| Scoring Alignments | |
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| Amino Acid Substitution Matrices | |
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| PAM Matrices | |
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| BLOSUM Matrices | |
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| Comparison between PAM and BLOSUM | |
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| Application of Substitution Matrices | |
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| The Number of Possible Alignments | |
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| Global Alignment | |
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| Shotgun Sequencing and Overlap Alignment | |
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| Local Alignment | |
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| Accommodating Affine Gap Costs | |
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| Maximizing vs. Minimizing Scores | |
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| Example Application of Global, Local, and Overlap Alignment | |
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| Summary | |
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| Further Reading | |
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| Exercises and Software Demonstrations | |
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| Biological Sequences and the Exact String Matching Problem | |
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| Exact vs. Inexact String Matching | |
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| Naive Pattern Matching | |
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| String Searching in Linear Time | |
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| Trees | |
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| Set Matching Using Keyword Trees | |
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| Suffix Trees | |
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| Suffix Tree Construction | |
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| Suffix Arrays | |
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| Repetitive Sequences in Genomics-the C-value Paradox | |
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| Detection of Repeated and Unique Substrings Using Suffix Trees | |
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| Maximal Repeats | |
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| Generalized Suffix Tree | |
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| Longest Common Substring Problem | |
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| k-Mismatches | |
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| Summary | |
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| Further Reading | |
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| Exercises and Software Demonstrations | |
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| Fast Alignment: Genome Comparison and Database Searching | |
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| Global Alignment | |
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| Local Alignment | |
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| Global/Local Alignment: k-Error Matching | |
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| Examples of Database Search Programs | |
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| Database Composition | |
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| Heuristic vs. Optimal Alignment Methods | |
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| Application: Determining Gene Families | |
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| Statistics of Local Alignments | |
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| Maximum Local Alignment Scores | |
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| Choosing a Substitution Matrix | |
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| Bit Scores | |
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| Summary | |
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| Further Reading | |
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| Exercises and Software Demonstrations | |
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| Multiple Sequence Alignment | |
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| Scoring Multiple Alignments | |
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| Multiple Alignment by Dynamic Programming | |
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| Heuristic Multiple Alignment | |
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| Summary | |
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| Further Reading | |
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| Exercises and Study Questions | |
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| Sequence Profiles and Hidden Markov Models | |
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| Profile Analysis | |
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| Hidden Markov Models | |
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| Profile Hidden Markov Models | |
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| Summary | |
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| Further Reading | |
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| Exercises and Software Demonstration | |
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| Gene Prediction | |
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| What is a Gene? | |
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| Computational Gene Finding | |
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| Measuring the Accuracy of Gene Predictions | |
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| Ab initio Methods: Searching for Signals and Content | |
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| Codon Usage | |
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| Finding Splice Sites with a Sequence Profile | |
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| Exon Chaining | |
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| Comparative Methods | |
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| General Remarks | |
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| Comparative Gene Prediction at the Adh Locus | |
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| Problems and Perspectives | |
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| Summary | |
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| Further Reading | |
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| Exercises | |
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| Sequences in Time | |
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| Phylogeny | |
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| Is There a Tree?-Statistical Geometry | |
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| Likelihood-Mapping | |
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| The Number of Possible Phylogenies | |
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| Distance Methods | |
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| Average Linkage Clustering | |
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| Neighbor-Joining | |
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| Maximum Parsimony | |
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| Maximum Likelihood | |
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| Searching Through Tree Space | |
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| Nearest Neighbor Interchange | |
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| Subtree Pruning and Regrafting | |
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| Branch and Bound | |
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| Bootstrapping Phylogenies | |
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| Summary | |
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| Further Reading | |
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| Exercises and Study Questions | |
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| Sequence Variation and Molecular Evolution | |
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| The Record of Past Events | |
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| Mutations and Substitutions | |
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| The Molecular Clock | |
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| Explicit Models of Molecular Evolution | |
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| Estimating Evolutionary Rates | |
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| Coding Sequences: Synonymous and Non-Synonymous Substitutions | |
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| Substitutions in Globin Sequences | |
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| Applications of K[subscript a]/K[subscript s] | |
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| A Language Gene? | |
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| Selection in the Human Genome | |
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| Summary | |
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| Further Reading | |
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| Exercises | |
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| Genes in Populations: Forward in Time | |
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| Polymorphism and Genetic Diversity | |
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| The Neutral Theory | |
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| Modeling Evolution Forward in Time | |
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| The Neutral Wright-Fisher Model | |
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| Fixation and Loss of Alleles | |
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| The Hardy-Weinberg Law | |
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| Fixation Probability and Time to Fixation | |
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| Loss of Genetic Diversity | |
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| Adding Mutation to the Model | |
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| Finite Alleles Model | |
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| Infinite Alleles Model | |
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| Infinite Sites Model | |
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| Mutation Drift Balance | |
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| The Rate of Fixation | |
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| Number of Alleles | |
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| Genetic Diversity | |
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| Sampling Alleles from Populations | |
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| Ewens' Sampling Formula | |
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| Application | |
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| Selection | |
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| Summary | |
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| Further Reading | |
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| Exercises and Software Demonstration | |
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| Genes in Populations: Backward in Time | |
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| Individuals' Genealogies vs. Gene Genealogies | |
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| Forward vs. Backward in Time | |
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| The Coalescent | |
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| Coalescent vs. Phylogenetic Trees | |
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| The Infinite Sites Model and the Number of SNPs | |
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| Mathematical Properties of the Neutral Coalescent | |
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| Tree Depth, Tree Size and the Number of Segregating Sites | |
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| Heterozygosity | |
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| The Distribution of Segregating Sites | |
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| Simulation Example | |
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| Recombination | |
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| Selection | |
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| Combining Recombination and Selection | |
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| Summary | |
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| Further Reading | |
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| Software Demonstrations and Exercises | |
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| Testing Evolutionary Hypotheses | |
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| Hudson-Kreitman-Aguade (HKA) Test | |
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| Tajima's Test | |
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| Fu and Li's Test | |
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| McDonald-Kreitman Test | |
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| Minimum Number of Recombination Events | |
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| Detecting Linkage Disequilibrium | |
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| Implementations | |
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| Summary | |
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| Exercises and Software Demonstration | |
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| Bioinformer | |
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| Alignment | |
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| Protein Substitution Matrices | |
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| Number of Alignments | |
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| Pairwise Alignment | |
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| Match | |
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| String Matching | |
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| Suffix Tree | |
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| Repeat Searching | |
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| Hash Table | |
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| Dotplot | |
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| Probability | |
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| Hidden Markov Model | |
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| Evolution | |
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| Phylogeny | |
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| Drift | |
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| Wright-Fisher | |
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| Coalescent | |
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| Probability | |
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| Molecular Biology Figures and Tables | |
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| Resources | |
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| Answers to Exercises | |
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| References | |
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| Glossary | |
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| Author Index | |
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| Subject Index | |