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来自 University of California San Diego 的课程

Comparing Genes, Proteins, and Genomes (Bioinformatics III)

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University of California San Diego

Comparing Genes, Proteins, and Genomes (Bioinformatics III)

78 个评分

课程 3（共 7 门，Specialization Bioinformatics）

Once we have sequenced genomes in the previous course, we would like to compare them to determine how species have evolved and what makes them different. In the first half of the course, we will compare two short biological sequences, such as genes (i.e., short sequences of DNA) or proteins. We will encounter a powerful algorithmic tool called dynamic programming that will help us determine the number of mutations that have separated the two genes/proteins. In the second half of the course, we will "zoom out" to compare entire genomes, where we see large scale mutations called genome rearrangements, seismic events that have heaved around large blocks of DNA over millions of years of evolution. Looking at the human and mouse genomes, we will ask ourselves: just as earthquakes are much more likely to occur along fault lines, are there locations in our genome that are "fragile" and more susceptible to be broken as part of genome rearrangements? We will see how combinatorial algorithms will help us answer this question. Finally, you will learn how to apply popular bioinformatics software tools to solve problems in sequence alignment, including BLAST.

从本节课中

Week 1: Introduction to Sequence Alignment

<p>Welcome to class!</p><p>If you joined us in the previous course in this Specialization, then you became an expert at <em>assembling</em> genomes and sequencing antibiotics. The next natural question to ask is how to compare DNA and amino acid sequences. This question will motivate this week's discussion of <strong>sequence alignment</strong>, which is the first of two questions that we will ask in this class (the algorithmic methods used to answer them are shown in parentheses):</p><ol><li>How Do We Compare DNA Sequences? (<em>Dynamic Programming</em>)</li><li>Are There Fragile Regions in the Human Genome? (<em>Combinatorial Algorithms</em>)</li></ol><p>As in previous courses, each of these two chapters is accompanied by a Bioinformatics Cartoon created by talented artist Randall Christopher and serving as a chapter header in the Specialization's bestselling <a href="http://bioinformaticsalgorithms.com" target="_blank">print companion</a>. You can find the first chapter's cartoon at the bottom of this message. Why have taxis suddenly become free of charge in Manhattan? Where did Pavel get so much spare change? And how should you get dressed in the morning so that you aren't late to your job as a crime-stopping superhero? Answers to these questions, and many more, in this week's installment of the course.</p><p><img src="http://bioinformaticsalgorithms.com/images/cover/alignment_cropped.jpg" width="528"></p>

(Check Out Our Wacky Course Intro Video!)4:01

与讲师见面

Pavel Pevzner
Professor
Department of Computer Science and Engineering
Phillip Compeau
Visiting Researcher
Department of Computer Science & Engineering
Nikolay Vyahhi
Visiting Scholar
Department of Computer Science and Engineering

Howdy, if you managed to stay awake in your high school biology class,

you might remember the central dogma of molecular biology.

It states that DNA makes RNA and that RNA serves as a template for

assembling amino acids into proteins according to the genetic code.

However, what your biology teacher may not have told you is that some bacteria

assembles certain many proteins without using an RNA template.

For example, some antibiotics,

molecular bullets that bacteria used to kill other bacteria.

And many proteins that do not rely on the genetic code and

instead use an even more complex, non-ribosomal code.

>> In this class we will see that, to crack this nonribosomal code,

we first need to learn how to compare giant proteins responsible for

the production of antibiotics and bacterial cells.

If we don't align these proteins correctly, then the elusive hidden message

revealing the nonribosomal code will disappear.

This is just one of many problems in modern biology

that relate to sequence comparisons.

To learn how to align sequences of individual genes and

proteins, we will take a sightseeing detour to Manhattan.

>> And after comparing individual genes,

we will zoom out to compare entire genomes containing billions of nucleotides.

We will see that for nearly every human gene, there is a.

However, this genes occur in very different arrangements on 1the human and

mouse chromosome.

These arrangements differ because our genomic architecture has

been shaped by rare and powerful mutations called genome rearrangement.

You can think of a genome rearrangement as a genomic earthquake that moves around

huge chunks of DNA, often from chromosome to.

Rearrangements also often shuffle [INAUDIBLE].

For example, some types of Leukemia are characterized by exchanging

large genomic segments between chromosomes 9 and 22.

By learning exactly where this rearrangement happens,

scientists developed a miracle drug called Gleevec that has saved

the lives of thousands of leukemia patients.

>> Now we're in California here.

Where earthquakes occur much more often than in most other places on the planet.

So our question that we are going to ask is,

does a similar phenomenon occur with genomic earthquakes?

In other words, are the breakage points of genome rearrangements

scattered throughout the human genome with no apparent rhyme or reason, or

do they occur at fragile regions, or genomic fault lines.

Where this breakage is occurring over and over again.

If yes, where are these fragile regions in the human genome and

how do they relate to cancer?

We hope that you're going to join us to decipher the nonribosomal code and

look for these fragile regions in the human genome.

>> Although these instructors may appear crazy they are not quite as mad

as they look.

Dr. Pavel Pevzner is a distinguished professor of computer science at

the University of California, San Diego and leading authority on bioinformatics.

He’s dressed this way because he sometimes thinks that he's

the sheriff of bioinformatics, a frontier discipline underpinning

the digital revolution in biology and personalized medicine.

Dr. Phillip Compeau is an assistant professor of computer science at

Carnegie Melon University.

To learn why he is dressed this way you'll need to take this course or

read the textbook.

Bioinformatics Algorithms,

An Active Learning Approach, coauthored by the two speakers.

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