Howdy! At the beginning of this century, scientists sequenced three billion nucleotides, making up the human genome. A breakthrough that changed the landscape of modern biology and initiated the era of personalized medicine. But what does it mean to sequence a genome? >> To illustrate how biologists sequence genomes, we want to give you a brain teaser. Imagine that we collect 100 copies of the June 27, 2000 edition of the New York Times. Now imagine that we put all these newspapers on a stack of dynamite. So, after we blow up all the newspapers into a crazy cloud of confetti, we want to give you a challenge. How is it that we would use all these scraps of newspaper that are just lying around to figure out what the news was on June 27, 2000? >> You're probably wondering what this crazy newspaper problem has to do with these genome sequences. Biologists cannot simply read the origin from beginning to end, in the way that you would read a book. What biologists can do is read very short pieces of DNA, but they do not know where in the genome these pieces belong. So they blast many of copies of your genome into millions of pieces and read each piece afterward. It is the job of a computer scientist to assemble the resulting, overlapping fragments of DNA into your genome. This is just like the newspaper problem that Philip described, and it is the largest puzzle that humans have ever tried to assemble. >> How is that we can put together a genome from millions of short fragments of DNA? To answer this question, we're going to need to travel back in time three centuries, when the residents of the city of Cunningsburgh had a question. Is it possible to start anywhere in this city, walk across each of its seven bridges exactly once, and then return back to where you started? >> You are probably wondering what this bridges of Cunningsburgh problem has to do with assembling genomes. In this class, we will see that genome assembly can be viewed as working through a giant city with millions of bridges, and visiting each bridge exactly once. >> After we learn how to assemble genomes, we'll also consider deciphering sequences of antibiotics, which are many proteins, or short strings of amino acids. Surprisingly, sequencing a million nucleotide long bacterial genome is much easier today, then sequencing just a short 10 to 15 amino acid long, antibiotic like daptomycin, which is used to treat life-threatening infections. As with genome sequencing, biologists sequence an antibiotic by first blasting many of its copies into tiny little pieces. However, unlike with genome sequencing, they are not able to read the amino acids that make up each of these pieces. Instead, biologists need to weigh them using an expensive molecular scale called a mass spectrometer. But how in the world can we sequence an antibiotic if all we know are the masses of its fragments? We hope that you'll join us on this wild trip to learn how to sequence the genomes in antibiotics by blowing them into tiny pieces and then trying to put them back together. >> 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 a 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 Mellon 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, co-authored by the two speakers.