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Bioinformatics Algorithms @ University of Kentucky

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How do we sequence and compare genomes? How do we identify the genetic basis for disease? How do we construct an evolutionary Tree of Life for all species on Earth? When you complete this interactive textbook, you will learn how to answer many questions in modern biology that have become inseparable from the fundamental algorithms used to answer these questions. This course features dozens of algorithmic challenges you to implement the bioinformatics algorithms that you will encounter along the way in dozens of automatically graded coding challenges that can be completed in any programming language! We recommend completing the material in the order presented, as each subsequent chapter will build on material from previous chapters.
Требования

Что нужно для старта

  • Learners should be good technical thinkers and have a strong introductory knowledge of programming. No biological background is necessary!
Аудитория

Для кого этот курс

  • Learners who are interested in seeing the fundamental algorithms that have made biology into a computational discipline.
Содержание

Программа курса

11 занятий
ТемаЧто внутри
01Where in the Genome Does Replication Begin?

- A Journey of a Thousand Miles. . .
- Hidden Messages in the Replication Origin
- Some Hidden Messages are More Surprising than Others
- An Explosion of Hidden Messages
- The Simplest Way to Replicate DNA
- Asymmetry of Replication
- Peculiar Statistics of the Forward and Reverse Half-Strands
- Some Hidden Messages are More Elusive than Others
- A Final Attempt at Finding DnaA Boxes in E. coli
- Epilogue: Complications in ori Predictions
- CS: Generating the Neighborhood of a String
- Detour: Big-O Notation
- Detour: Probabilities of Patterns in a String
- Detour: The Most Beautiful Experiment in Biology
- Detour: Directionality of DNA Strands
- Detour: The Towers of Hanoi
- Detour: The Overlapping Words Paradox

02Which DNA Patterns Play the Role of Molecular Clocks?

- Do We Have a "Clock" Gene?
- Motif Finding Is More Difficult Than You Think
- Scoring Motifs
- From Motif Finding to Finding a Median String
- Greedy Motif Search
- Motif Finding Meets Oliver Cromwell
- Randomized Motif Search
- How Can a Randomized Algorithm Perform So Well?
- Gibbs Sampling
- Gibbs Sampling in Action
- Epilogue: How Does Tuberculosis Hibernate?
- CS: Solving the Median String Problem
- Detour: Gene Expression
- Detour: DNA Arrays
- Detour: Buffon's Needle
- Detour: Complications in Motif Finding
- Detour: Relative entropy

03How Do We Assemble Genomes?

- Exploding Newspapers
- The String Reconstruction Problem
- String Reconstruction as a Walk in the Overlap Graph
- Another Graph for String Reconstruction
- Walking in the de Bruijn Graph
- The Seven Bridges of Königsberg
- Euler's Theorem
- From Euler's Theorem to an Algorithm for Finding Eulerian Cycles
- Assembling Genomes from Read-Pairs
- Epilogue: Genome Assembly Faces Real Sequencing Data
- CS: The Effect of Gluing on the Adjacency Matrix
- CS: Generating All Eulerian Cycles
- CS: Reconstructing a String from the Paired de Bruijn Graph
- CS: Maximal Non-Branching Paths in a Graph
- Detour: A Short History of DNA Sequencing Technologies
- Detour: Repeats in the Human Genome
- Detour: An Introduction to Graphs
- Detour: Hamilton's Icosian Game
- Detour: Tractable and Intractable Problems
- Detour: From Euler to Hamilton to de Bruijn
- Detour: The Seven Bridges of Kaliningrad
- Detour: The BEST Theorem
- Detour: Pitfalls of assembling double-stranded DNA

04How Do We Sequence Antibiotics?

- The Discovery of Antibiotics
- How Do Bacteria Make Antibiotics?
- Dodging the Central Dogma of Molecular Biology
- Sequencing Antibiotics by Shattering Them into Pieces
- A Brute Force Algorithm for Cyclopeptide Sequencing
- A Branch-and-Bound Algorithm for Cyclopeptide Sequencing
- Mass Spectrometry Meets Golf
- From 20 to More than 100 Amino Acids
- The Spectral Convolution Saves the Day
- Epilogue: From Simulated to Real Spectra
- CS: Generating the Theoretical Spectrum of a Peptide
- CS: How Fast is CyclopeptideSequencing?
- CS: Trimming the Peptide Leaderboard
- Detour: Gause and Lysenkoism
- Detour: The Discovery of Codons
- Detour: Quorum Sensing
- Detour: Molecular Mass
- Detour: Selenocysteine and Pyrrolysine
- Detour: Pseudo-polynomial Algorithm for the Turnpike Problem
- Detour: Split genes

05How Do We Compare Biological Sequences?

- Cracking the Non-Ribosomal Code
- Introduction to Sequence Alignment
- The Manhattan Tourist Problem
- Sequence Alignment is the Manhattan Tourist Problem in Disguise
- An Introduction to Dynamic Programming: The Change Problem
- The Manhattan Tourist Problem Revisited
- From Manhattan to an Arbitrary DAG
- Backtracking in the Alignment Graph
- Scoring Alignments
- From Global to Local Alignment
- The Changing Faces of Sequence Alignment
- Penalizing Insertions and Deletions in Sequence Alignment
- Space-Efficient Sequence Alignment
- Epilogue: Multiple Sequence Alignment
- Detour: Fireflies and the Non-Ribosomal Code
- Detour: Finding an LCS without Building a City
- Detour: Constructing a Topological Ordering
- Detour: PAM Scoring Matrices
- Detour: Divide-and-Conquer Algorithms
- Detour: Scoring Multiple Alignments

06Are There Fragile Regions in the Human Genome?

- Of Mice and Men
- The Random Breakage Model of Chromosome Evolution
- Sorting by Reversals
- A Greedy Algorithm for Sorting by Reversals
- Breakpoints
- Rearrangements in Tumor Genomes
- From Unichromosomal to Multichromosomal Genomes
- Breakpoint Graphs
- Computing the 2-Break Distance
- Rearrangement Hotspots in the Human Genome
- Epilogue: Synteny Block Construction
- CS: From Genomes to the Breakpoint Graph
- CS: Solving the 2-Break Sorting Problem
- Detour: Why is the Gene Content of X Chromosomes So Conserved?
- Detour: Discovery of Genome Rearrangements
- Detour: The Exponential Distribution
- Detour: Bill Gates and David X. Cohen Flip Pancakes
- Detour: Sorting Linear Permutations by Reversals

07Which Animal Gave Us SARS?

- The Fastest Outbreak
- Transforming Distance Matrices into Evolutionary Trees
- Toward An Algorithm for Distance-Based Phylogeny Construction
- Additive Phylogeny
- Using Least Squares to Construct Approximate Phylogenies
- Ultrametric Evolutionary Trees
- The Neighbor-Joining Algorithm
- Character-Based Tree Reconstruction
- The Small Parsimony Problem
- The Large Parsimony Problem
- Epilogue: Evolutionary Trees Fight Crime
- Detour: When Did HIV Jump from Primates to Humans?
- Detour: Searching for a Tree Fitting a Distance Matrix
- Detour: The Four Point Condition
- Detour: Did Bats Give Us SARS?
- Detour: Why Does the Neighbor-Joining Algorithm Work?
- Detour: Computing Limb Lengths in the Neighbor-Joining Algorithm
- Detour: Giant Panda: Bear or Raccoon?
- Detour: Where Did Humans Come From?

08How Did Yeast Become a Wine Maker?

- An Evolutionary History of Wine-Making
- Identifying Genes Responsible for the Diauxic Shift
- Introduction to Clustering
- The Good Clustering Principle
- Clustering as an Optimization Problem
- Farthest First Traversal
- k-Means Clustering
- The Lloyd Algorithm
- Clustering Genes Implicated in the Diauxic Shift
- Limitations of k-means Clustering
- From Coin Flipping to k-Means Clustering
- Making Soft Decisions in Coin Flipping
- Soft k-Means Clustering
- Hierarchical Clustering
- Epilogue: Clustering Tumor Samples
- Detour: Whole Genome Duplication or a Series of Duplications?
- Detour: Measuring Gene Expression
- Detour: Microarrays
- Detour: Proof of the Center of Gravity Theorem
- Detour: Gene Expression Matrix to a Distance/Similarity Matrix
- Detour: Clustering and Corrupted Cliques

09How Do We Locate Disease-Causing Mutations?

- What Causes Ohdo Syndrome?
- Introduction to Multiple Pattern Matching
- Herding Patterns into a Trie
- Preprocessing the Genome Instead
- Suffix Trees
- Suffix Arrays
- The Burrows-Wheeler Transform
- A First Attempt at Inverting the Burrows-Wheeler Transform
- The First-Last Property and Burrows-Wheeler Inversion
- Pattern Matching with the Burrows-Wheeler Transform
- Speeding Up Burrows-Wheeler Pattern Matching
- Where are the Matched Patterns?
- Burrows and Wheeler Set Up Checkpoints
- Epilogue: Mismatch-Tolerant Read Mapping
- CS: Constructing a Suffix Tree
- CS: Solving the Longest Shared Substring Problem
- CS: Partial Suffix Array Construction
- Detour: The Reference Human Genome
- Detour: Rearrangements, Insertions, & Deletions in Human Genomes
- Detour: The Aho-Corasick Algorithm
- Detour: Suffix Arrays and Suffix Trees
- Detour: Binary Search

10Why Have Biologists Still Not Developed an HIV Vaccine?

- Classifying the HIV Phenotype
- Gambling with Yakuza
- Two Coins Up the Dealer's Sleeve
- Finding CG-Islands
- Hidden Markov Models
- The Decoding Problem
- Finding the Most Likely Outcome of an HMM
- Profile HMMs for Sequence Alignment
- Classifying Proteins with Profile HMMs
- Are Profile HMMs Really All That Useful?
- Learning the Parameters of an HMM
- Soft Decisions in Parameter Estimation
- Baum-Welch Learning
- The Many Faces of HMMs
- Epilogue: Nature is a Tinkerer and not an Inventor
- Detour: The Red Queen Effect
- Detour: Glycosylation
- Detour: DNA Methylation
- Detour: Conditional Probability

11Was T. rex Just a Big Chicken?

- Paleontology Meets Computing
- Which Proteins are Present in this Sample?
- Decoding an Ideal Spectrum
- From Ideal to Real Spectra
- Peptide Sequencing
- Peptide Identification
- Peptide Identification and the Infinite Monkey Theorem
- Spectral Dictionaries
- T. rex Peptides: Contaminants or Ancient Treasure Trove?
- Epilogue: From Unmodified to Modified Peptides (Part 1)
- Epilogue: From Unmodified to Modified Peptides (Part 2)
- Detour: Gene Prediction
- Detour: Finding All Paths in a Graph
- Detour: The Anti-Symmetric Path Problem
- Detour: Transforming Spectra into Spectral Vectors
- Detour: The Infinite Monkey Theorem
- Detour: The Probabilistic Space of Peptides in a Dictionary
- Detour: Are Terrestrial Dinosaurs Really the Ancestors of Birds?

01Where in the Genome Does Replication Begin?

- A Journey of a Thousand Miles. . .
- Hidden Messages in the Replication Origin
- Some Hidden Messages are More Surprising than Others
- An Explosion of Hidden Messages
- The Simplest Way to Replicate DNA
- Asymmetry of Replication
- Peculiar Statistics of the Forward and Reverse Half-Strands
- Some Hidden Messages are More Elusive than Others
- A Final Attempt at Finding DnaA Boxes in E. coli
- Epilogue: Complications in ori Predictions
- CS: Generating the Neighborhood of a String
- Detour: Big-O Notation
- Detour: Probabilities of Patterns in a String
- Detour: The Most Beautiful Experiment in Biology
- Detour: Directionality of DNA Strands
- Detour: The Towers of Hanoi
- Detour: The Overlapping Words Paradox

02Which DNA Patterns Play the Role of Molecular Clocks?

- Do We Have a "Clock" Gene?
- Motif Finding Is More Difficult Than You Think
- Scoring Motifs
- From Motif Finding to Finding a Median String
- Greedy Motif Search
- Motif Finding Meets Oliver Cromwell
- Randomized Motif Search
- How Can a Randomized Algorithm Perform So Well?
- Gibbs Sampling
- Gibbs Sampling in Action
- Epilogue: How Does Tuberculosis Hibernate?
- CS: Solving the Median String Problem
- Detour: Gene Expression
- Detour: DNA Arrays
- Detour: Buffon's Needle
- Detour: Complications in Motif Finding
- Detour: Relative entropy

03How Do We Assemble Genomes?

- Exploding Newspapers
- The String Reconstruction Problem
- String Reconstruction as a Walk in the Overlap Graph
- Another Graph for String Reconstruction
- Walking in the de Bruijn Graph
- The Seven Bridges of Königsberg
- Euler's Theorem
- From Euler's Theorem to an Algorithm for Finding Eulerian Cycles
- Assembling Genomes from Read-Pairs
- Epilogue: Genome Assembly Faces Real Sequencing Data
- CS: The Effect of Gluing on the Adjacency Matrix
- CS: Generating All Eulerian Cycles
- CS: Reconstructing a String from the Paired de Bruijn Graph
- CS: Maximal Non-Branching Paths in a Graph
- Detour: A Short History of DNA Sequencing Technologies
- Detour: Repeats in the Human Genome
- Detour: An Introduction to Graphs
- Detour: Hamilton's Icosian Game
- Detour: Tractable and Intractable Problems
- Detour: From Euler to Hamilton to de Bruijn
- Detour: The Seven Bridges of Kaliningrad
- Detour: The BEST Theorem
- Detour: Pitfalls of assembling double-stranded DNA

04How Do We Sequence Antibiotics?

- The Discovery of Antibiotics
- How Do Bacteria Make Antibiotics?
- Dodging the Central Dogma of Molecular Biology
- Sequencing Antibiotics by Shattering Them into Pieces
- A Brute Force Algorithm for Cyclopeptide Sequencing
- A Branch-and-Bound Algorithm for Cyclopeptide Sequencing
- Mass Spectrometry Meets Golf
- From 20 to More than 100 Amino Acids
- The Spectral Convolution Saves the Day
- Epilogue: From Simulated to Real Spectra
- CS: Generating the Theoretical Spectrum of a Peptide
- CS: How Fast is CyclopeptideSequencing?
- CS: Trimming the Peptide Leaderboard
- Detour: Gause and Lysenkoism
- Detour: The Discovery of Codons
- Detour: Quorum Sensing
- Detour: Molecular Mass
- Detour: Selenocysteine and Pyrrolysine
- Detour: Pseudo-polynomial Algorithm for the Turnpike Problem
- Detour: Split genes

05How Do We Compare Biological Sequences?

- Cracking the Non-Ribosomal Code
- Introduction to Sequence Alignment
- The Manhattan Tourist Problem
- Sequence Alignment is the Manhattan Tourist Problem in Disguise
- An Introduction to Dynamic Programming: The Change Problem
- The Manhattan Tourist Problem Revisited
- From Manhattan to an Arbitrary DAG
- Backtracking in the Alignment Graph
- Scoring Alignments
- From Global to Local Alignment
- The Changing Faces of Sequence Alignment
- Penalizing Insertions and Deletions in Sequence Alignment
- Space-Efficient Sequence Alignment
- Epilogue: Multiple Sequence Alignment
- Detour: Fireflies and the Non-Ribosomal Code
- Detour: Finding an LCS without Building a City
- Detour: Constructing a Topological Ordering
- Detour: PAM Scoring Matrices
- Detour: Divide-and-Conquer Algorithms
- Detour: Scoring Multiple Alignments

06Are There Fragile Regions in the Human Genome?

- Of Mice and Men
- The Random Breakage Model of Chromosome Evolution
- Sorting by Reversals
- A Greedy Algorithm for Sorting by Reversals
- Breakpoints
- Rearrangements in Tumor Genomes
- From Unichromosomal to Multichromosomal Genomes
- Breakpoint Graphs
- Computing the 2-Break Distance
- Rearrangement Hotspots in the Human Genome
- Epilogue: Synteny Block Construction
- CS: From Genomes to the Breakpoint Graph
- CS: Solving the 2-Break Sorting Problem
- Detour: Why is the Gene Content of X Chromosomes So Conserved?
- Detour: Discovery of Genome Rearrangements
- Detour: The Exponential Distribution
- Detour: Bill Gates and David X. Cohen Flip Pancakes
- Detour: Sorting Linear Permutations by Reversals

07Which Animal Gave Us SARS?

- The Fastest Outbreak
- Transforming Distance Matrices into Evolutionary Trees
- Toward An Algorithm for Distance-Based Phylogeny Construction
- Additive Phylogeny
- Using Least Squares to Construct Approximate Phylogenies
- Ultrametric Evolutionary Trees
- The Neighbor-Joining Algorithm
- Character-Based Tree Reconstruction
- The Small Parsimony Problem
- The Large Parsimony Problem
- Epilogue: Evolutionary Trees Fight Crime
- Detour: When Did HIV Jump from Primates to Humans?
- Detour: Searching for a Tree Fitting a Distance Matrix
- Detour: The Four Point Condition
- Detour: Did Bats Give Us SARS?
- Detour: Why Does the Neighbor-Joining Algorithm Work?
- Detour: Computing Limb Lengths in the Neighbor-Joining Algorithm
- Detour: Giant Panda: Bear or Raccoon?
- Detour: Where Did Humans Come From?

08How Did Yeast Become a Wine Maker?

- An Evolutionary History of Wine-Making
- Identifying Genes Responsible for the Diauxic Shift
- Introduction to Clustering
- The Good Clustering Principle
- Clustering as an Optimization Problem
- Farthest First Traversal
- k-Means Clustering
- The Lloyd Algorithm
- Clustering Genes Implicated in the Diauxic Shift
- Limitations of k-means Clustering
- From Coin Flipping to k-Means Clustering
- Making Soft Decisions in Coin Flipping
- Soft k-Means Clustering
- Hierarchical Clustering
- Epilogue: Clustering Tumor Samples
- Detour: Whole Genome Duplication or a Series of Duplications?
- Detour: Measuring Gene Expression
- Detour: Microarrays
- Detour: Proof of the Center of Gravity Theorem
- Detour: Gene Expression Matrix to a Distance/Similarity Matrix
- Detour: Clustering and Corrupted Cliques

09How Do We Locate Disease-Causing Mutations?

- What Causes Ohdo Syndrome?
- Introduction to Multiple Pattern Matching
- Herding Patterns into a Trie
- Preprocessing the Genome Instead
- Suffix Trees
- Suffix Arrays
- The Burrows-Wheeler Transform
- A First Attempt at Inverting the Burrows-Wheeler Transform
- The First-Last Property and Burrows-Wheeler Inversion
- Pattern Matching with the Burrows-Wheeler Transform
- Speeding Up Burrows-Wheeler Pattern Matching
- Where are the Matched Patterns?
- Burrows and Wheeler Set Up Checkpoints
- Epilogue: Mismatch-Tolerant Read Mapping
- CS: Constructing a Suffix Tree
- CS: Solving the Longest Shared Substring Problem
- CS: Partial Suffix Array Construction
- Detour: The Reference Human Genome
- Detour: Rearrangements, Insertions, & Deletions in Human Genomes
- Detour: The Aho-Corasick Algorithm
- Detour: Suffix Arrays and Suffix Trees
- Detour: Binary Search

10Why Have Biologists Still Not Developed an HIV Vaccine?

- Classifying the HIV Phenotype
- Gambling with Yakuza
- Two Coins Up the Dealer's Sleeve
- Finding CG-Islands
- Hidden Markov Models
- The Decoding Problem
- Finding the Most Likely Outcome of an HMM
- Profile HMMs for Sequence Alignment
- Classifying Proteins with Profile HMMs
- Are Profile HMMs Really All That Useful?
- Learning the Parameters of an HMM
- Soft Decisions in Parameter Estimation
- Baum-Welch Learning
- The Many Faces of HMMs
- Epilogue: Nature is a Tinkerer and not an Inventor
- Detour: The Red Queen Effect
- Detour: Glycosylation
- Detour: DNA Methylation
- Detour: Conditional Probability

11Was T. rex Just a Big Chicken?

- Paleontology Meets Computing
- Which Proteins are Present in this Sample?
- Decoding an Ideal Spectrum
- From Ideal to Real Spectra
- Peptide Sequencing
- Peptide Identification
- Peptide Identification and the Infinite Monkey Theorem
- Spectral Dictionaries
- T. rex Peptides: Contaminants or Ancient Treasure Trove?
- Epilogue: From Unmodified to Modified Peptides (Part 1)
- Epilogue: From Unmodified to Modified Peptides (Part 2)
- Detour: Gene Prediction
- Detour: Finding All Paths in a Graph
- Detour: The Anti-Symmetric Path Problem
- Detour: Transforming Spectra into Spectral Vectors
- Detour: The Infinite Monkey Theorem
- Detour: The Probabilistic Space of Peptides in a Dictionary
- Detour: Are Terrestrial Dinosaurs Really the Ancestors of Birds?

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