Assembling Genomes and Sequencing Antibiotics (Bioinformatics II)

开始时间: 04/22/2022 持续时间: Unknown

所在平台: CourseraArchive 课程类别: 计算机科学 大学或机构: University of California, San Diego （加州大学圣地亚哥分校） 授课老师： Phillip E. C. Compeau Pavel Pevzner

课程主页: https://www.coursera.org/course/assembly

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课程详情

In "Finding Hidden Messages in DNA", we discussed how to separate some of the signal from the apparent noise of DNA sequences.  But how do we know what the DNA sequence making up a genome is in the first place?  After all, DNA nucleotides are far too small to view with a normal microscope, and biologists still do not possess technology that would read all the nucleotides of your genome from beginning to end.

In the first chapter of this course, we will see that entire genomes are assembled from millions of short overlapping pieces of DNA.  The scale of this problem (the human genome is 3 billion nucleotides long!) implies that computers must be involved. Yet the problem is even more complex than it may appear ... to solve it, we will need to travel back in time to meet three famous mathematicians, and learn about algorithms based on graph theory.

In the second chapter of the course, we will consider antibiotics, which are mini-proteins engineered by bacteria to fight each other. Determining the sequence of amino acids making up an antibiotic is an important problem for medical research, but the practical barriers to sequencing an antibiotic containing just 10 amino acids are often more substantial than the limitations when assembling a genome with 10 million nucleotides! To decode the amino acid sequence of an antibiotic, biologist must blast many copies of this antibiotic into pieces and use an expensive molecular scale to weigh the resulting fragments. It may not seem possible that we can determine an antibiotic just from the masses of these fragments, but we will see that brute force algorithms will often succeed.

课程大纲

How Do We Assemble Genomes? (Graph Algorithms)

• 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 Konigsberg
• 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

How Do We Sequence Antibiotics? (Brute Force Algorithms)

• The discovery of antibiotics
• How do bacteria make antibiotics?
• Dodging the Central Dogma
• Sequencing antibiotics by shattering them into pieces
• A brute force algorithm for cyclopeptide sequencing
• A branch-and-bound algorithm for cyclopeptide sequencing
• Just how fast is this algorithm?
• Adapting cyclopeptide sequencing for spectra with errors
• From 20 to more than 100 amino acids
• The spectral convolution saves the day
• Epilogue: From simulated to real spectra

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