 Good afternoon ladies and gentlemen My name is Yashik Singh and I am from the Department of Telehealth at the Nelson-Armandela School of Medicine in South Africa This presentation is going to give you a brief description of what bioinformatics is We're going to speak about why bioinformatics is important give you some examples of Bioinformatics applications and we're going to specifically look at some sequencing tools and some uses of sequencing Before we start with the bio bioinformatics lecture proper. It's important for us to know some background information A very important point for us to realize is that Bases are the building blocks of all organic matter So bases combined with each other to form DNA The four different bases that are actually used when creating DNA are adenine, guanine, cytosine and thymine And these are shown in the bottom right-hand corner of this slide These bases join to a pentose ring via a glycosidic bond and creates what is called a nucleoside The nucleoside then combines with either one, two or three Phosphates and are called nucleotides You get a nucleotide monophosphate if one phosphate group is joined to this pentose ring and base if two phosphates are joined. It's called the nucleotide diphosphate and If three are joined. It's called a triphosphate So in order to better explain how this Bases combine with each other to form the helix of the DNA. Please watch this first video So from this video, we realize that the bases combine in a certain Specific way in a certain order to create DNA DNA is then converted to RNA and then from RNA to Proteins and proteins are really a whole group of amino acids link together each triplet of The the bases So you see here TTT, TTC, TTA, TTG Each triplet actually codes for a particular amino acid. There are 22 amino acids 20 of these are encoded using these triplet RNA nucleotides Eight of these Amino acids are essential amino acids, which means that the body cannot create these amino acids themselves It has to be ingested with diet so From from this 20 amino acid if you look at an example TTT when when joined together actually creates the amino acid phenyl alanine But sometimes things go wrong Mutations occur when bases don't interact with each other correctly it forms changes in the amino acids and Changes in the amino acids can result in changes in the proteins and the way we see things These mutations can either be inherited for instance diseases like sickle cell disease or Cystic fibrosis some cancers or they can be acquired For instance, there are some birth defects due to a radiation Leukemia HIV resistance. These are all acquired changes in the DNA which results in different diseases and different And and different types of sicknesses So now that we know why The genome why the DNA why bases why amino acids are so important We realize that the study of this is actually a valuable and that's where bioinformatics comes in Bioinformatics is an applied science and that means that it takes The knowledge of different fields and puts it together to solve some sort of problem If we had to try and find a single definition of bioinformatics We might think of something that states that Bioinformatics is an applied science that uses domains like applied mathematics informatics statistics computer science Artificial intelligence chemistry biochemistry etc to solve problems at the molecular level And this is what differs bioinformatics from the other informatics fields or sub-disciplines in medical informatics Bioinformatics deals were problems at the molecular level So things like genes like the amino acid we spoke about like how mutations in the DNA Cause different types of diseases. How can these mutations be identified? How can they be prevented? How can they be even reversed? so there are many different areas of bioinformatics and Googling them you would find That there are thousands and thousands of websites and webpages actually describing different uses or different aspects of Bioinformatics and this is mainly because it's such an applied field You get sequence alignment gene finding genome assembly protein structure alignment protein structure prediction predict products of gene expression protein-protein interactions and modeling of evolution of These the three most important or the three most Highly researched fields are sequence alignment Predicting products of gene expression and modeling of evolution and in this lecture. We're going to speak mainly about sequence alignment Predicting the products of gene expression is Absolutely vital and this field deals with trying to predict how these bases would interact with each other to actually produce the DNA How amino acids interact with which with each other to actually produce the protein the shape of the protein for instance Modeling of evolution is basically trying to create an environment that you can control Electronically and you can see how how different drugs for instance react As the environment is changed. You can see how for instance HIV drug Resistance samples blood samples of patients would react to certain drugs in a in a Computer's using a computer science program instead of injecting these drugs for them and then testing So it's actually just modeling evolution how things change over time So sequence analysis in the most simplest sense is taking two Sequences that we spoke about before either amino acid nucleotides Nucleosides just any two sequences and actually trying to align them so that there is maximum overlap You're trying to see how close two sequences are together and there are many uses of why you'd want to do this For instance, if there is a new virus That that that is playing mankind and you're unsure of how to start off Creating an antiviral for this you can compare the Sequence the DNA of this virus to a database of viruses and Then find the one that is most close to this new virus and use the antivirals for that virus in the database as they start to actually finding the new antiviral sequence alignment has been used to Determine the type of HIV you have there are some studies that show that the type of HIV that you have actually Actually The type of HIV you have Actually affects the way in which you respond to treatment HIV treatment By sequencing you can actually find out how close you are to other species And that's probably one of the reasons why We can do things like take a heart from a pig and put into a human body Because we know from the DNA how close we are to the pig Searching genes now with searching genes when we are trying to align them together There's a specific algorithm that is used. It's not as simple as just Putting two sequences over each other and trying to see which letters overlap We have to look at all possible combinations in Aligning them and also take into account that insertions and deletions may also occur in the sequence One algorithm that is used for this and probably the most common one is the blast algorithm In the demonstration, we actually going to use the blast algorithm to show you how this works So the first demonstration is the demonstration on finding the subtype of HIV In this demonstration, I take an unknown Subtype sequence I put the sequence into a Program in bio Africa this program takes a sequence it compares it against its database and sees what type of subtype that is The second part of the demonstration is Stanford's HIV DB Website where I show you how Mutations in the DNA is actually used to determine what drugs a patient will be resistant to in HIV therapy The next this the other half of this video is actually trying to show you another use of Sequence alignment and that is proving to you almost a theory of evolution Showing you how close we are to the chimp. So I take two sequences. I take the sequence of the Chimp and I take the sequence of the human and I compare them together using the blast algorithm and I'll show you how similar they are together. So please watch the video called the video to now so we all know that Sequence information is now vital in in medicine Especially now that we are moving towards personalized medicine where medicine is not going to be a List of symptoms that you are asked and then you are given general medication for that In in years to come we'll find the medicine is going to become Individualized where a sample of your blood is going to be taken your DNA is going to be Sequenced or parts of the DNA will be sequenced And that will be used to determine Best medication for you, especially in chronic disease So this use of bioinformatics the use of genome information will actually result in new diagnostic and prognostic information But there are two important things for us to actually consider One is that genome data is very large And when we are creating electronic medical record systems, we have to take this into consideration We have to build the systems In such a way that we ensure that different parts of this data can be accessed easily By different programs that need it But more importantly, we need to start thinking about the ethical and security considerations of having and using genomes Imagine if a medical aid company or an insurance company gets a hold of your genome somehow and They can now predict what drugs you are going to or what drugs you'll be resistant to in the future They cannot predict what diseases you are going to have in the future. What are the likelihood of those diseases? going to be and Is it ethical for them to use this information? And it and increase your medical aid subscription or increase your life insurance subscription or not give you medical aid or life insurance Also, if a doctor uses this algorithm and and and realizes that in the future, you may have some sort of incurable degenerative disease Should he tell you if it's if there's if It's if he just uses the algorithm to act to determine that you are going to have this disease There is in fact no guarantee that you will there's a chance and depending on how good the algorithm is There may be a good chance But does that mean that he has to tell you that you that you will suffer from this disease? What happens if you take this badly and commit suicide or do do other irresponsible things So there are many ethical considerations and also design considerations when you are thinking about use of this type of tools in clinical informatics Thank you very much for your time