Bioinformatics Specialization

Named a top 50 MOOC of all time by Class Central! This course begins a series of classes illustrating the power of computing in modern biology. Please join us on the frontier of bioinformatics to look for hidden messages in DNA without ever needing to put on a lab coat. In the first half of the course, we investigate DNA replication, and ask the question, where in the genome does DNA replication begin? We will see that we can answer this question for many bacteria using only some straightforward algorithms to look for hidden messages in the genome. In the second half of the course, we examine a different biological question, when we ask which DNA patterns play the role of molecular clocks. The cells in your body manage to maintain a circadian rhythm, but how is this achieved on the level of DNA? Once again, we will see that by knowing which hidden messages to look for, we can start to understand the amazingly complex language of DNA. Perhaps surprisingly, we will apply randomized algorithms, which roll dice and flip coins in order to solve problems. Finally, you will get your hands dirty and apply existing software tools to find recurring biological motifs within genes that are responsible for helping Mycobacterium tuberculosis go "dormant" within a host for many years before causing an active infection.

You may have heard a lot about genome sequencing and its potential to usher in an era of personalized medicine, but what does it mean to sequence a genome? Biologists still cannot read the nucleotides of an entire genome as you would read a book from beginning to end. However, they can read short pieces of DNA. In this course, we will see how graph theory can be used to assemble genomes from these short pieces. We will further learn about brute force algorithms and apply them to sequencing mini-proteins called antibiotics. In the first half of the course, we will see that biologists cannot read the 3 billion nucleotides of a human genome as you would read a book from beginning to end. However, they can read shorter fragments of DNA. In this course, we will see how graph theory can be used to assemble genomes from these short pieces in what amounts to the largest jigsaw puzzle ever put together. In the second half of the course, we will discuss antibiotics, a topic of great relevance as antimicrobial-resistant bacteria like MRSA are on the rise. You know antibiotics as drugs, but on the molecular level they are short mini-proteins that have been engineered by bacteria to kill their enemies. Determining the sequence of amino acids making up one of these antibiotics is an important research problem, and one that is similar to that of sequencing a genome by assembling tiny fragments of DNA. We will see how brute force algorithms that try every possible solution are able to identify naturally occurring antibiotics so that they can be synthesized in a lab. Finally, you will learn how to apply popular bioinformatics software tools to sequence the genome of a deadly Staphylococcus bacterium that has acquired antibiotics resistance.

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.

In the previous course in the Specialization, we learned how to compare genes, proteins, and genomes. One way we can use these methods is in order to construct a "Tree of Life" showing how a large collection of related organisms have evolved over time. In the first half of the course, we will discuss approaches for evolutionary tree construction that have been the subject of some of the most cited scientific papers of all time, and show how they can resolve quandaries from finding the origin of a deadly virus to locating the birthplace of modern humans. In the second half of the course, we will shift gears and examine the old claim that birds evolved from dinosaurs. How can we prove this? In particular, we will examine a result that claimed that peptides harvested from a T. rex fossil closely matched peptides found in chickens. In particular, we will use methods from computational proteomics to ask how we could assess whether this result is valid or due to some form of contamination. Finally, you will learn how to apply popular bioinformatics software tools to reconstruct an evolutionary tree of ebolaviruses and identify the source of the recent Ebola epidemic that caused global headlines.