Good morning, everyone. Before we begin, will someone open us with the word of prayer, please? Let's pray. Have any further? We just thank you for this time of study. Father, as we commit this time of study into their hands, we pray that whatever we learn today, we will be able to retain whatever we learn and apply the same in our lives, Father. We also pray for a blessing upon all of our community members and all the students here. In Jesus' precious name we pray. Amen. Okay. So just a reminder about your exam. I haven't checked to see how many of you have done it. But if you haven't yet done it, you have till the end of Monday. For those who did it, it was everything okay. Do you have any issues? Okay. We'll talk more about it maybe on Monday once everyone or on the next Thursday once everyone has finished it. Also on Monday, our classes will be online, right? For all the in-person students, our Monday class will be online. So I can just join on Google Classroom. Okay. Let's begin. We are quite behind in this class. So we're going to try and catch up on as much as we can do over the next few weeks. Okay. So we finished with the Gospels and Acts and now we're going into the Epistles. Now a majority of the Epistles we know are written by Paul. So we have an introduction to Paul in our textbook just to help us understand who he is and how he has influenced so much of the New Testament. We probably are all very familiar with a lot about Paul, but this is just to give us some perspective into the letters. So we start with his sense of divine vocation. So Paul had a clear sense of his calling. So we see multiple records where he goes back to his encounter with Christ on the road to Damascus and he uses that as he's testifying to people about who Jesus is. So that encounter with Christ for him was a very powerful encounter of being a personal witness to the resurrected Christ and having a sense of burden or calling to share this with all those who didn't know the Gospel. In Galatians 1-2 he talks about, I'll just read the verse for us, I did not receive it from any man, nor was I taught it, rather I received it by revelation from Jesus Christ. So he also had this sense of all that he was sharing had come to him from Christ himself, right, because he didn't have anyone come to him and share the Gospel with him. So he met Christ on the road to Damascus and then he went and he was introduced to other believers and grew in his own faith. So he understood that his revelation had first come from Christ himself. And so he had that confidence in everything that he was sharing that it could be trusted. It was not taught by man, but taught by God himself. So in Corinthians 9-16, for when I preach the Gospel, I cannot boast since I am compelled to preach, go to me if I do not preach the Gospel. So that sense of feeling compelled refers to having an outside pressure put on you, like recognizing that there is a need that you need to respond to. That is the way Paul felt. He had experienced God's grace so powerfully that he felt that pressure that others need this grace and I need to be the one to take it to them. And he was willing to do whatever it took, cross whatever seas he had to cross in order to take that grace to other people. Another thing that comes through really powerfully in his epistles is a sense of authority. He speaks to people knowing that his authority comes from God. So even if he is writing like we look at the book of Romans, he is writing to believers that he has not personally met. But he is able to talk to them with authority that comes from God. He has no fear, he has no sense of like he needs to shy away from speaking the truth to people. He'll correct people, he'll rebuke people, he'll praise people with confidence that God has put him in this place of leadership over the church. So knowing that it was something that had come from God himself. His love for his converts, as we're looking through the letters, we'll see this, that everything he says comes from a place of love. So while he also has this sense of authority that I'm speaking as God has led me to speak, he also does it in love. That balance of truth and love is there in his letters. So even if he's correcting people, even if he's calling out sin in the church, he's doing it from a place of love, wanting to see them stay true to Christ, wanting to see them not fall away from the faith. So it's a great example for church leaders that we hold on to love and we hold on to truth. We don't let go of either one of those when we are leaving people. So we're willing to address the difficult things, willing to call out sin, but we do it in a way that comes from a place of love. His convictions, so he talks about, we see a lot of things where he's talking about doctrine. So he has actually contributed to our understanding of the Christian doctrine in a very, very big way. So because so much of the New Testament is written by him, whatever we understand about salvation, about justification, about redemption, about sanctification, all of that is what he has written down in the letters. And he writes it according to the situation that he's addressing. So he's very aware of what is the issue in that church and how do I bring these doctrines out to address their situation? So from a particular problem, he'll arrive at universal application. So writing to their situation, but also bringing out a doctrine that can be applied universally, so in all the churches for all time. So these are some of the examples we already talked about, justification, salvation, grace, and his conviction coming from a deep and direct experience with God. We see also Paul's willingness, 1 Corinthians 9, 22b, I have become all things to all people so that by all possible means, I might save some. So what does that mean? What does that reflect about Paul's ministry? It means that no matter what the cost, he was willing to pay the cost. On the other hand, he's talking specifically about understanding the context of the people he's serving. To the Jews he became like a Jew, to the Gentiles he became like a Gentile. That is, he didn't force the Gentiles to follow Jewish law, neither did he force the Jews to give up on their law. He understood their context, their culture and he presented the gospel in a way that was relevant to them. At the same time, he didn't water down the gospel. So to say that he didn't give up on certain truths or give up on certain principles just to make it easily acceptable for people. He held on to the truth but held on to the main truths. So he was able to separate culture from the truth and he was able to present truth in a way that was culturally relevant to his audience. So that was something that he recognized the difference between what is important, what is necessary and what we can be flexible with in our faith, in our practice. Another is the same thing, to have a genuine concern to see things from another person's point of view. His language and style, he writes in very good Greek and he was also trained as a Bible scholar. He was not trained as a public speaker but in ancient times all writing was done in a style where you are convincing the people that you are writing to. So he uses that kind of writing which is called rhetorical style of writing. Structure of the letters, we'll see there's an introduction, there'll be greetings to the people he's writing to. He may raise certain things that are happening in the church then he'll raise concerns about things that are not going right. He'll write all of that in the body of the letter and then greetings and a benediction. That's a general structure for letters at that time. We also see him going through a lot of suffering, specifically in the Book of Acts we read about all of his travels and things that he's experienced. So imprisonments, beatings, stoning, shipwrecks, hazards from any sources both natural and human, lack of food, scantiness of clothing. All of that were his experience as he went on these mission trips. He sacrificed a lot because of that conviction of what he was doing, the work that he was doing. The importance of it, the necessity of it and a heart for the lost. All of that made it worth all of the sacrifice that he made for the Gospel. So Paul's epistles can be classified into four different categories basically based on the theme of the epistle. So we have the soteriological epistles, the Christological epistles, the ecclesiological epistles and the eschatological epistles. Lots of big words but we look at what do each of those mean. So the soteriological epistles focus on salvation. What does it mean to be saved by Jesus Christ? The Greek word soteria means salvation comes from the word soter which means saviour. Romans talks about justification so today depending on how much time we have we might just get an introduction to some of that. Talks about justification once for all, sanctification day by day and sanctification in personal life, in our personal lives. First and second Corinthians talks about salvation in the church. So how does salvation impact the life of the church? And then Galatians talks about salvation by grace not by work. So Galatians was a very important book in the Reformation because talking about salvation that comes by grace not by the works that we do was one of the main things that brought the church out of a works mentality to trusting in Christ sacrifice for salvation. The Christological epistles focus on Christ the Anointed One and emphasize the person and work of Christ. So we see in Philemon talking about how Jesus has paid the cost for our sins. So you all have a class in Christology, right? Have you already done that? Y'all are doing it this semester. So Y'all have probably already talked about all of this and gone into all of these books. But yeah, paying the price for our sins, Christ the head of the church, Christ the body of Christ and the humiliation of Christ in his incarnation and his subsequent exaltation. So all of these come from Philemon, Colossians, Ephesians and Philippians. As we look through those books individually, we'll be able to see how Paul brings out each of these themes about Christ in these books. The ecclesiological epistles, which means it focuses on the church itself taken from the Greek word ecclesia. We see 1st Timothy and Titus talking about what are the qualifications required of church leaders. So if you are in a place of leadership in the church, what kind of requirements must be placed on leaders? How should they live their personal lives, their faith lives, their family lives and what kind of character should they have? 2nd Timothy talks about diligence and faithfulness of continuing in our faith, especially for a church that was going to face a lot of apostasy. So people going away from the church, falling away from the faith. So Paul writes this last letter to Timothy and in this letter he's encouraging him to encourage the church to stay strong in their faith. So that they don't fall away from the faith when temptation comes or when wrong teaching comes or when persecution comes. Then we have the eschatological epistles, which is taken from the word eschatos, means last. And it focuses on Christ's second coming, so the last days in the return of Christ. 1st Thessalonians talks about the second coming of Christ and 2nd Thessalonians talks about false teaching regarding the second coming of Christ. So warning people about false teaching regarding Christ's second coming and teaching them about what is true, what is right. So this focuses on the end times basically. With that we can go into the book of Romans. So some background on the book of Romans, we see in Acts 1921 that Paul had planned to go to visit Rome. If someone can just read Acts 1921 for us. Acts 1921, when these things were accomplished, Paul purposed in the spirit when he had passed through Macedonia and Achaia to go to Jerusalem saying, after I have been there, I must also see Rome. So we see right here, Paul having that sense of calling and purpose of I want to go to Rome, I want to go to the gospel in Rome. But if we read Romans 113, Paul says that he has not yet, he has longed to go there, but he has not yet been able to go. So that's about 10 years later than this verse that we read in Acts 19. So for 10 years, he had not yet been able to go to Rome, but was only after that about three years later. So 13 years later, which we come to the end of Acts, we read about Paul being imprisoned right at the end of acts. For two years, he was in prison. That is when he actually reaches Rome. So he goes as a prisoner to Rome, and that's when he meets with the Jewish leaders and starts to minister to them. So we know that Romans is written by Paul because it says so in Romans 11 where Paul himself introduces himself. And he introduces himself using the word dooloi, which is a slave or born servant, which means that he had given himself over completely to his master. He'd given up his rights, he'd given up his freedom to his master, and he would forever for the rest of his life be under his master's rule. This is different from other words that he could have used. So there's mistyos, which is a hired servant. So someone who could at any time decide that they no longer wanted to work under their master and could leave. Or diaconos, which is the word for deacon in English. And that is someone who serves prompted by love.  So he hasn't used that kind of word where I'm serving you for the benefit of what Christ wanted from him. And he is serving from a place of love, but he doesn't choose to use that word. That word was used much more for leaders in the church. The word diacon was used for leaders in the church. Rather, he uses the born servant or slave as a reference to himself. And then we have at the end of Acts that this was written by his secretary Tertius. So somebody else wrote the letter, Paul narrated it, and Tertius wrote it down. So letters in the New Testament are actually much, much longer than letters that were written in that time, in that culture. Usually there would be about 87, it would be the length of about 87 words, letters would be. But these letters are so much longer because they contained such important messages for the churches that they were going to. And so we see this letter would have taken multiple hours. Paul would have recited this letter to the secretary. It would have taken approximately 10 to 11 hours of recitation and writing for them to actually finish writing this letter. Date and location. So usually it's estimated that it's between 55 to 58 AD, but 57 or 58 AD is likely when Romans was written. This is during the last three months of Paul's third missionary journey. So he goes on his third missionary journey. He returns to Jerusalem and that's when he's arrested. So he writes this during those last three months while he's in Greece. And this is just before he returns to Jerusalem with the offering for the poor that he's collected from all the churches. And the recipients, we see in chapter one itself that it's addressed to those who have been called to belong to Jesus Christ in Rome. So basically written to the church in Rome. We see also personal greetings to many people. So we know from the beginning of Romans that Paul has never visited Rome. But still at the end of the book, he is writing personal greetings to several people and naming several people in the church. So he already knew a lot of people in the church, although he had never visited there. So the one possibility is that as he was doing the missionary journeys, he met some of these people in other places. If you all remember when we talked about Priscilla and Aquila, I don't know if I mentioned this in class. But Priscilla and Aquila had been asked to leave because of Emperor Claudius. All of the Jews were sent away from Rome because Claudius and generally the Roman government felt that there was a lot of controversy being raised by the Jews. They were basically causing strife between other faiths because they were talking about Christ. So the Jews were sent out of Rome and it's possible that during this time, Paul was able to meet a lot of them in his missionary journeys, which is why he knows so many of them and he's still able to name them in the last chapter. So because a lot of the Jews had been sent out of Rome, Paul is writing mostly to Gentile Christians because the church was made up of mostly Gentile Christians at that time. Paul writes soon after Claudius' death and it was after Claudius' death that Jews started to come back to Rome. So they started to come back to the church. So if we see in Romans, we see this whole thing of salvation to the Jews and then to the Gentiles, like judgment for the Jews and for the Gentiles. There is this distinction being made between the Jews and Gentiles. It's because the church was going through a transition, right? The church had become a Gentile church for a long time because the Jews had left and now the Jews were starting to come back after Claudius' death. So there were also these cultural differences, these differences in how they were practicing their faith that were causing issues within the church. And so Paul is addressing that through this letter. Even as he's talking about salvation through Christ, he's also saying that we are all one in Christ. Even if we are Jews, whether we are Gentiles or Jews, that salvation in Christ makes us one. So if someone can just read Romans 1, 5 for us, Romans 1, 5 and 6. Romans 1, 5 and 6, through whom we have received grace and a postal ship to bring about the obedience of faith for the sake of his name among all the nations, including you who are called to belong to Jesus Christ. Okay, thank you. You read both 5 and 6, right? Yes. So we see here a very clear emphasis on the Gentiles here. So he says, through him we received grace and a postal ship to call all the Gentiles to the obedience that comes from faith for his name's sake. And you also are among those Gentiles who are called to belong to Christ. So right there we see that focus on the Gentile Christians being emphasized. But we'll also later on see how he is distinguishing between Jew and Gentile. One example here is Romans 1, 16. It says, for I am not ashamed of the gospel because it is the power of God that brings salvation to everyone who believes. First to the Jew and then to the Gentile. So that distinction between Jews and Gentiles. This is one of the key verses in the book of Romans talking about how salvation has come to all people. And that is what the focus of Romans is on salvation in Jesus Christ. But what that salvation means for us. Romans 5 1, if someone can read this for us, you can either read from here or open it in your Bible. Romans 5 1, therefore having just been justified by faith, we have peace with God through our Lord Jesus Christ. So this is one of the other themes in Romans is justification. From salvation, Paul moves on to what does that salvation mean for us now. It means that we have been justified in Christ. And what does justification, how does justification impact us? So keywords Christ and faith are used multiple times in Romans. And the main theme of Romans is our redemption. So in the first 11 chapters, it focuses more on the doctrine of redemption. So salvation, justification, sanctification. And then on verses 12 to 16 talks about the practical. So what does it mean now that we are saved, now that we are justified? How should we live our lives as Christians? And so chapters 12 to 16 will focus on the practical side of being believers, being people who are saved and sanctified in Christ. So everyone understands the meaning of these three words. Salvation, justification, sanctification. Yes, okay. So we will just go on. Unique features. The book of Romans is a pretty complete summary of Christian doctrine. It covers the very basic tenets of the Christian faith. So it's a very good foundational document for the church and for believers as well to understand what does it mean to be saved. And we see also that Paul quoted a lot from the Old Testament much more than he does in his other 12 letters. Just going to show that the Old Testament is a key to our understanding of what it means to be saved. So to understand salvation, we go back to what the Old Testament talked about. How do we understand our salvation in the light of that? Comparison with other biblical books. In Genesis, we see Abraham being the patriarch of Israel. In Romans, he is the patriarch of all who believe. So we see that Paul goes back to when Abraham was actually justified. He was not justified at the point of circumcision. He was justified when he believed the promise that God gave him regarding his inheritance. That he would have children and God would bless him with an inheritance. So that is when he was declared as being righteous because of his faith. So because his faith came before circumcision, he is the father of all who believe. And so it moves from this theme in Genesis of Abraham being the father of the Israelites to being the father of all who believe, even Gentiles. In Galatians, we see a discussion of justification by faith. It's like a shorter version of what Romans talks about. So Romans has a much more detailed description of justification. And Galatians being a shorter book just has all of that summarized into a few chapters. In the book of James, we see that he talks about the fruit of salvation. So Romans talks about the root of salvation, that is faith. So it is through faith that we are saved. And James talks about what is the result of that salvation, which is that we should be doing good works. So those are the three books that we can compare Romans to. So with that, we'll just begin with an outline in Romans until chapter 5, starting with chapter 1. So Romans chapter 1 begins with just an introduction. So he's following the general structure of letters in that day. So he begins with greetings to the church, begins with introduction of himself, and talks about what he's going to talk about in the rest of the book. Just to give them an introduction to what his main intent is in writing the book. With that, he then goes into his talk on justification itself. From chapters 1, 18 to 3, 20, he's talking about how all people, the universal need for justification. So all people need to be justified. Verses 18 to 32, he talks about the Gentiles being guilty. Chapters 2 to 3, 8, the Jews being guilty. And then goes on to all the world being guilty. Chapter 3 verses 9 to 20. So we'll just read some of the key verses from there. If someone can read Romans 132. Romans 132, through the know God's decree that those who practice such things deserve to die. They not only do them, but give approval to those who practice them. So this is regarding the Gentiles. So the Gentiles know God has revealed himself to all people through, even if you look at nature, you will ask questions about who has created this. And so that should lead people to seek God. But these people have willingly rejected God, knowing that there is a God. They've rejected him and not only rejected him, but also approved of people who walk in sin. And so these first few verses talk about how they are guilty because they have rejected God. Chapters 2 to 3, 8, the Jews are guilty. Can someone read chapter 2 verse 13 and then verse 25? For it is not those who hear the law, who are righteous in God's sight. But it is those who obey the law, who will be declared righteous. Thank you and verse 25. Circumcision has value if you observe the law, but if you break the law, you have become as though you had not been circumcised. So here in this chapter and in chapter 3, he is talking about how the Jews also have not followed the law. And so just because they have the law doesn't mean they are righteous. Only if they have followed the law that they will be declared righteous. And then we will read chapter 3 verse 20. Someone can read that. Romans chapter 3 verse 20. For by works of the law, no human being will be justified in his sight. Sins through the law comes knowledge of sin. Thank you. So the final conclusion at the end of this section is that no one can be saved by the law. The law only helps us to see our sin, but we will never be made righteous through the works of the law. And then he goes on in the following section 321 to chapter 4 to talk about the fact that being made righteous or being justified will only is only possible through faith in Christ. So he talks about God's righteousness by faith if someone can read verse chapter 3 verse 25. Romans chapter 3 verse 20. Okay. Now please go ahead sister. Thank you. Whom God put forward as a propitiation by his blood to be received by faith. This was to show God's righteousness because in his divine forbearance he had passed over former sins. Thank you. Was that 325? Romans 325. Yes, pastor. Okay. So here he talks about Jesus being the sacrifice for sin. People are made right with God when they believe that Jesus sacrificed his life shedding his blood. So talking about we are all guilty. The Gentiles are guilty. The Jews are guilty. And there is no way we can be saved by the law, but it is through faith in Christ that we are justified. So he introduces that and then goes into chapter 4 where he goes back to Abraham and David talking about the fact that they were declared righteous and they were justified based on faith and not based on the law. Like we talked about Abraham was declared righteous before he was circumcised. So it was not by the works of the law, but by his faith that he was declared righteous. So we will just close with Romans chapter 5. We will continue from there on Monday. In Romans chapter 5, this is actually quite a key chapter, so I would encourage you all or maybe we can just read it quickly. If somebody can read this chapter for us, Romans chapter 5, 21 verses. We can read and close with Romans 5. Therefore, since we have been justified through faith, we have peace with God through our Lord Jesus Christ, through whom we have gained access by faith into this grace in which we now stand. And we boast in the hope of glory, the glory of God. Not only so, but we also glory in our sufferings because we know that suffering produces perseverance, perseverance, character and character hope. And hope does not put us to shame because God's love has poured out into our hearts through the Holy Spirit who has been given to us. You see, at just the right time when we were still powerless, Christ died for the ungodly.  But God demonstrates his own love for us in this. While we were still sinners, Christ died for us. Since we have now been justified by his blood, how much more shall we be saved from God's wrath to him? For if, while we were God's enemies, we were reconciled to him through the death of his son, how much more having been reconciled shall we be saved through his life? Not only is this so, but we also boast in God through our Lord Jesus Christ, through whom we have now received reconciliation. Therefore, just as sin entered the world through one man and death through sin, and in this way death came to all people because all sinned. To be sure, sin was in the world before the law was given, but sin is not charged against anyone's account where there is no law. Nevertheless, death ranged from the time of Adam to the time of Moses, even over those who did not sin by breaking a command, as did Adam, who is the pattern of the one to come. But the gift is not like the trespass, for if the many died by the trespass of the one man, how much more did God's grace and the gift that came by the grace of one man, Jesus Christ, overflowed to the many? Nor can the gift of God be compared with the result of one man's sin. The judgment followed one sin and brought condemnation, but the gift followed many trespasses and brought justification. For if by the trespass of one man, death reigned through that one man, how much more will those who receive God's abundant provision of grace and of the gift of righteousness reign in life through the one man, Jesus Christ. Consequently, just as one trespass resulted in condemnation for all people, so also one righteous act resulted in justification and life for all people. For just as though the disobedience of the one man, the many were made sinners, so also through the obedience of the one man, the many will be made righteous. The law was brought in so that the trespass might increase, but where sin increased, grace increased all the more. So that just as sin reigned in death, so also grace might reign through righteousness to bring eternal life through Jesus Christ our Lord. Thank you. So we see this key chapter in the book of Romans talking about how we are justified. It is through Christ. So Christ is the new head under which all of us find ourselves. Whereas before Christ we were all under Adam's headship and therefore the sin of Adam was upon all of us. Now for all who believe in Christ, we are under Christ and the righteousness of Christ is imputed to all of us. That is we all are declared righteous because we are under the headship of Christ. So that is the kind of key from which the rest of Romans will continue. So we'll continue from there from Monday on Monday. If you'll have any questions, we can address that. If not, we can close. Okay. Then we will see you back on Monday in the online classroom for everyone. Thank you, Sister. Thank you.


So whatever you wish to do, you must bring yourself to moment of joy and clarity within yourself. At that moment, what you decide, even if you die, you must go by that. Whenever your emotions go up and down, your mind says many things, that's not important. In the moment of clarity, when I'm saying joy, because when you're happy, you're not compulsive. When you're very happy and clear, at that time, if you look at things and see, yes, this is what is more sensible for me, just do that. It doesn't matter if it feels like hell, because that's where your well-being is. When you're in different states of compulsiveness, if you make decisions as to which way to turn, you will be endlessly lost.


So in this webinar, I will be talking about the regulatory landscape in terms of privacy law and privacy obligations that impacts on researchers, in particular when personal information can be used or disclosed for research, some of the common privacy issues that come up for researchers, in particular around what consent means and if you're going to rely on consent, what does a valid consent look like? And also de-identification, what does de-identification mean under the Privacy Act? Also talking briefly about new developments in privacy law, the General Data Protection Regulation, which is a European privacy law with reach into Australia, as well as notifiable data breaches and when that might impact on people in the research community at whatever organisation you're at, and then just briefly what's coming next in terms of privacy law developments, which leads down to some of the other speakers for this webinar.


Thanks, Gene. I'd like to thank you all for being here today and provide you a welcome on behalf of NHGRI, National Human Genome Research Institute, also on behalf of ENCODE, and hopefully this will be a useful experience for you. We have a couple of important objectives we'd like to tell you about ENCODE, what it is and how it can be used. But also very important, this is two ways we'd like to hear from you all. What are ways that the resource, the presentation of the resource, or the presentation of these outreach efforts could be made more useful to the community? You're here as a group that can help us to hear more about that. This picture at the bottom here, this is the ENCODE consortium, or some fraction of it. And my heart goes out to these people who work very hard to develop all of this data and do all of this analysis that you're going to be hearing a lot about. This large group of people has worked very hard to create this, and I want to thank them. Going off to the right are program colleagues of mine from National Human Genome Research. Elise Feingold was at the beginning of the project and started it out, and Dan Gilchrist, my colleague, is here with us meeting today. So I'm going to tell you a little bit about the ENCODE resource, what's the rationale for it, what is it, and how is it made, a little bit about how it can be used to study human disease. That's not all that it can be used for, but that's one important application, and a little bit about how to access ENCODE materials. To me, ENCODE makes me think in some ways of music. It has collections of lots of different things. They all work together. There's not the one thing that matters or the one thing that's important, but depending on what you're doing, you may care more about one instrument or another or what kind of music, and the same kind of thing takes place in ENCODE. So the reason for ENCODE, I think, is quite clear. The completion of the human genome project became obvious that understanding much of the genome is difficult. Understanding what portions of the genome are doing something of value is difficult. We have a genetic code that tells us about protein coding regions, but that's a very small part of the genome that's very sparse, right? So how do we find the regulatory regions? How do we find out what they're doing and how to identify them as another problem? And this is important because we know that non-coding DNA does a lot of important things. The vast majority of common disease associations and heritability of the associations is imputed to lie in non-coding regions. So that's important. There are Mendelian disorders that are caused by genetic variation in non-coding regions. So by those two measures, among others, non-coding DNA is important. But it's not easy to study, and this functional information could be used to interpret disease, gene regulation, mechanisms of mutation, and so forth. If we had a better understanding on it. So ENCODE is one project a lot of individual investigators are also working in this area trying to get a better understanding of these issues. Here's a graphic way to see the problem. If you just take a snippet of the genome, not a random snippet, but a snippet, looking at it quickly, it's difficult for most people to get information out of it. Now, to some extent, this is an exaggeration, right? We all know that partially this is a solved problem. You can have maps like at the bottom of the slide where you can mark exons and you can mark variants that are associated with disease where you can do the same thing by color coding the sequence. And that gives you some information now that you didn't get just from looking at the sequence. But I would argue that this is still pretty sparse in terms of information content, even though this is very valuable. So the approach that ENCODE is taking, a lot of individual investigators are doing this as well, is to build richer maps so that we might have more information. So how this might work is now you can see the same GWAS variant in context of a gene. This comes from non-ENCODE work. And from ENCODE data, you can see that there are biochemical signatures in this region, and we'll explain what they might look like. And it turns out that this is the signature for a candidate regulatory region. So that tells you something about this variant could lie in a regulatory region. ENCODE data can tell you other stuff because it's cell type specific. You can see that this information is preferentially coming from a particular cell type. So that may give you some idea of what cell type is important in this process. And while this variant appears to lie within a particular gene, you can see that easily from a sequence alignment. There are ways to predict what gene it might be work with. This is, of course, predictive, not known with certainty. In this case, the prediction is that this, if it's a regulatory variant, is actually working to control the neighboring genes. So being able to have these stories moving forward would help us to much better appreciate the role of genetic variants and phenotypic traits. So the goals of ENCODE are really simple to state. How to get to this is another story. We're trying to identify all of the candidate functional elements in the genome. We're also trying to share this resource freely with the community. That really means it's unrestricted access, not controlled access. There's no login. There's no purchase. You simply go to the website, use whatever it is that you want. And people are using this to look at the genetic basis of disease, gene regulation, how mutation occurs, and so forth. But any process that you'd like to use it for is allowed. So the way ENCODE is doing this resource is built upon decades of research and gene regulation. For years, people have known different biochemical signatures are associated with gene regulation transcription, post-transcriptional processes. And these have been converted into genome-wide assets. And then the results of these are used to sort of reverse engineer to make predictions about how the genome is working. So you can make predictions about where genes are. That's probably the simplest part. What are the transcripts that are encoded within those genes? And then what are regulatory elements, such as promoters, enhancers, and other distal regulatory elements that might be controlling those genes? So a big shout-out to the gene regulation community that has over many years developed these techniques. And ENCODE data are very cell-type specific, which is both an advantage and a drawback to doing this. It's a drawback because you need to collect the data in many different cell fates and cell states, unlike to first approximation with DNA sequencing. But then it gives you richer information, because the answers that you get back tell you something about what cell types are involved. And if you look at differentiation over time, total potent cells start off with one set of candidate regulatory elements. Some of those are extinguished over time. New cells, new elements appear to be turned on and progenitor cells, and then other elements turn on and fully differentiated cells. So these changes in regulatory element signature tell us about cell fate. So to date ENCODE has done a lot of useful things that I think help out the community. We're sharing thousands of data sets. Today they're shared without any embargo. There's no wait one year until the consortium has had a chance to publish on it, say. They're shared through unrestricted access. The equivalent of GO, there's no signing up for DBGAP or buying an account or something to access the data. The data are uniformly processed to a large extent, which minimizes the chance of coming up with cross data set comparison and finding differential effects that aren't real, their analysis are effects. We're also sharing the software that we've either produced or used in the project so others can use it and also to make things transparent. We're working with other projects, other individual investigators, to make the data more interoperability, talking about standards and how things are communicated. One of the things that we share that we share are ENCODE publications, and there are hundreds that have come from the consortium, but perhaps for this audience more important, there are over a thousand publications from outside of ENCODE that have used ENCODE data. Some of these look at human disease, some of these look at basic biology, and they cover a wide spectrum of diseases, and I think that this attests to the translational value of their resource. So in summary, we're trying to create a catalog of all the functional elements of the genome. This is freely shared with the community. The foundation for this is established techniques and methodologies that have been used for years in gene regulation studies. And these maps can be used to make predictions about genome function, which can help you in other work. So now we're going to take a quick peek at how you might use ENCODE to study the role of genetic variation in human disease. And here I'm going to give you a few use cases, some ideas that I've gleaned from the literature. This is not the only sum total of what can be done. The major idea here is that ENCODE supports hypothesis generation and refinement. High throughput data are useful in identifying hypotheses to test. And some of these things are predicting causal variants for traits or diseases, predicting target genes for either regulatory elements or genetic variants, cell types that are affected by regulatory elements or variants, and then also predicting upstream regulators understanding the pathways of how these systems work. So prediction of causal variants, to some this is obvious problem, to others it's not obvious that this is an issue. But if one does a study such as GWAS, you get a locus, but there are other variants that are in LD. So that doesn't tell you, just from that first step, what is the causal variant? ENCODE type annotations can be used as one fine mapping strategy. You've also got the issue that it's possible that multiple variants work on the same trait or disorder. You might not be trying to find the causal variant, rather a group of them. So ENCODE data can help you to figure that out. And a recently published study looked at ENCODE and Common Fund or Roadmap Epigenomics data and found that many GWAS findings overlap with these annotations. So that suggests that this could be used. If one is not familiar with these kinds of assays, the simplest way to get started is there are a couple of pre-computed resources. First, I'll tell you about Haplorag from Manolis Kellis's group at MIT that can help you to sort through ENCODE and roadmap data. And with Haplorag, you can, step one, put in genomic coordinates or SNPIDs or a list of them and then click Submit, and then it will return pre-computed analysis of ENCODE data. This is just the first step of the kind of result that you get returned. And it'll show you for both the lead SNP and others that are in LD, what kinds of ENCODE and roadmap annotations are found in that area. And that can help guide you in further experiments to decide what you want to do next. Similarly, Mike Snyder's group and Mike Cherry's group, both at Stanford, developed regular MDB. And in a different way, this analyzes ENCODE data, roadmap data, and some other data sources. Again, you can put in genomic coordinates or SNPIDs and then click Move On and initially, you're presented with a score. The likelihood that the genomic region you're looking at has regulatory potential. And then, of course, you can drill down and see the individual underlying data and see why that assessment came about. As Gene said at the beginning, and I meant to say at the beginning, but forgot, please don't worry about writing down URLs or detailed explanations. All of these slides are going to be shared. So that information will be available to everybody. There's also ENCODE SysElement browser, and this has a number of different functions for human data and mouse data. And in this example, you can again put in a genomic coordinate and it will find candidate regulatory elements. In this case, it finds them by looking for DNAs, hypersensitive sites, and also tell you about candidate upstream regulators by looking for motifs that are found in those regions. Now, prediction of target genes is also an interesting problem. Gtex and ENCODE data and other projects are finding that it's not unusual that regulatory sites don't work on the nearest gene. They work on some gene that's further away. So if one finds a piece of DNA that you think is important and it's not protein coding, if you just guess that the nearest gene is its target, the growing story is you'll be wrong at least half the time, okay? And if we look at, for instance, predictions based on GWAS studies, a lot of times it's quite distant, that the regulatory region is from the gene. And in a practical sense, what this could mean is you might have some variant of interest and start studying the nearest gene, but perhaps there's a better candidate that one could work with, a better prediction. And that could change your research project if you didn't have to spend a few months studying one gene, studying the next where your only filter was proximity. If you knew other principled ways to say what was the likely candidate, you could come up with a better answer. So you can do this by using regulatory elements database. Terry Fury's lab developed this and it works a number of different ways. One of the things you can do is put in genomic coordinates and it'll again report DNAs, hypersensitive sites in that region, candidate regulatory regions. And if you click on any of them, it tells you additional information. And one of the things that we'll tell you is if there's a prediction for what gene is the likely target of that, it will give you a confidence estimate and what that target gene might be. The encodes this element browser, which I pointed out before. And in the bottom of these slides, you can see that you're gonna be hearing more about this in workshop session three, for example. So this is just a very quick overview. But again, you can put in a gene name and this tool will return to what are regulatory elements that appear, what are candidate regulatory elements that might be linked to this gene. And the one that I've highlighted here is one that I showed in that initial example of showing a common control region that affected many genes. I chose that example because in mouse that's been very well worked out that region's been knocked out. And it does in fact control these genes. If you go to encode human data, you could make the same prediction without having known any of that. And last use case I'll tell you about is predicting target cell types. Again, to some people this is surprising that this is something you would need to do to others it's intuitive. But if you think about most human diseases, most human diseases affect several cell types. Sometimes they affect several cell types directly. Sometimes it's more subtle. For instance, sometimes the affected cell type is a developmental niche for the cell type that actually shows the dramatic effect. There are people who have lack of lymphocytes because their thymus, the niche where lymphocytes develop is impaired. So the affected cell type is not where that gene appears. And sometimes of course the etiology of diseases is not well understood. I'm old enough to be able to remember when it was a wild and crazy idea that type one diabetes, a metabolic disorder might involve the immune system. And we now know it's an autoimmune disorder, but for some fraction of diseases that we work on today, we don't know the cell types. So again, in regulatory elements database, if you call up different elements, in some cases those elements appear to be active in only some cell types. Other elements appear to be broadly utilized. So that could give you some information about cell type that's affected. Similarly, if you look at haplorag and RegulomDB, which I talked about briefly, when you see the underlying evidence, if for instance you mouse over something in haplorag, it tells you the cell types that that data came from. And that could guide your hypothesis, especially if something is known about the disease. If you think Alzheimer's, okay, neurons, macrophages, glial cells and your hit is for glial cells, right? Then that helps you to refine things. It's more difficult to use if nothing is known about the disease. And if we look in the ECODE SysElement Browser, and for instance, look at gene expression, you can type in a mouse or human gene name. It might be the gene that you think is important in that disease is expressed in a restricted number of cell types, obviously. Some other genes are broadly expressed. And that again could guide your hypothesis as to what's going on. A more principled way to do this is you could take regulate, you could intersect genetic variants that are linked to a disorder, so intersect them with those with regulatory elements and then ask whether those regulatory elements are enriched in particular cell types. And the code for doing this is shared at this URL on the slide. And then you can ask in a more principled way which of several candidate cell types might be involved in a particular disorder or process. So in summary, I think the main thing that ENCODE can help with is hypothesis generation and refinement. And that this can be used to predict causal variants, to predict target genes, to predict cell types and upstream regulators. All of the examples I've showed you are examples of how you could use this with genetic results. If you had epigenetic results or an epigenetic cohort, you could do many of the same things within code data. Of course, if you're skilled in that, then you know that some additional caveats apply. The same kind of thing I've shown germline examples, but one could do all of this with somatic variants, but again, additional caveats apply when you have that. So now I'm gonna quickly run through how you can access ENCODE materials. You're gonna hear a lot more about this at least in workshops two, one, and five. So the ENCODE portal, ENCODEproject.org, that's the one URL I would want you to remember, ENCODEproject.org, has a lot of this info. And for instance, you can access the data under either search or matrix. If you go to matrix, there's a nice representation, which I've crudely trimmed, so you can't see most of it. It shows you the kind of data that's offered, data types, projects that the data come from, and so forth. And you can use facets to narrow down the subset of the data that you wanna see. I wanna emphasize the data policy. As I said in the beginning, this is freely shared. So if the data are there, you can use it. There's no restriction, no embargo or anything. We do ask the standard scientific thing that cite the project that if you, like with any other data source, if you use something, cite it. For reasons of transparency and reproducibility, it's good to share accession numbers. If you share the accession numbers of what you did, then your peers can tell what you did and how you did it. Okay. New to the ENCODE portal is the search by region. You can put in a genomic coordinate or SNPID, find ENCODE data that overlaps with that region and visualize it. That's a quick way for those of you that wanna see tracks or to download elements to get to data. There's an ENCODE encyclopedia.  This'll be the focus of workshop one, all right? And it has high level and very close to the data analysis. It has a range of things. Ground level close to the data annotations of things like where are transcription factors bound. Middle level annotations are putting the data together to find things like where are promoters and enhancers and how can you visualize them. And then top level annotations put together many different types of data to generate inferences. You'll be hearing about that, especially in workshop five. ENCODE publications. Again, there are community publications that I would point out to you because there are examples of how people outside of ENCODE are using the data to study human disease, to study basic biology, to produce software tools. But there are also ENCODE publications that again illustrate what was done and how the data can be used. We're very interested in sharing the standards for how things are done and this is done again for the same two reasons, for transparency so that you know what was done and how it was done so you can evaluate for yourself how credible this is. And then we're also sharing these standards because there are many people in the field that are including some that are newer in the field and they're wondering how should I be doing this? We hold this out as one way that you can do it but of course it's for each group to decide how to do it. We don't dictate standards to anybody. So you can click through and see different types of standards and experiment documents that we share. We're sharing software that we're using in the project again so that people can understand what was done and how it was done or if people are doing this kind of work and want to use software. Some of this software was created by ENCODE, some of this software was created outside of the project but we use it heavily so they're both important to know about and we share both of those kinds of software. And lastly I'd like to give a shout out to our partners in the International Human Epigenomes Consortium. ENCODE is a member of this as is the NIH Common Fund Project Roadmap Epigenomics. A bunch of like-minded projects are collecting epigenomic data across many cell types and sharing them through different mechanisms. The IHEC data portal and project summary are available. There's lots of useful data there including a subset of the ENCODE data. So I want to finalize here with a list of URLs that I don't expect you to read now or write down now. Again all of these slides are shared and you can click on the links rather than write them down but we share for instance tutorials from the project including the results of this, we'll get posted online, analysis tools in the portal and then IHEC resources. I'd highlight the ENCODE mailing list. If you want to hear regular updates on the project you can join this list. So I'll conclude by reminding you that the goals of ENCODE are to find all of the candidate functional regions in the genome. This is an aspirational goal. I think there's no way to know when it's done or how it's done. And we're freely sharing the results that we find as a resource with the community. And ENCODE data are already being used in studies of human disease and human biology and they can be used any way that anyone can come up with. I'll stop here by thanking the people on the ENCODE consortium first. Here's another representation of some of them. I have the privilege of working with smart people every day and hearing great ideas and it makes my job really fun. And my program colleagues at NHGRI, Elise and Peter Goode started the ENCODE project long before. I had anything to do with it. Dan Gilchrist and I work on the project now along with Elise and Dan is here today. Courage you to say hi to Dan as well. And they're great colleagues and people to work with. And of course all of this work like any other bit of science is built on years of study that came before it. Lots of work on gene regulation. Lots of work on genetic basis of human disease. So I'll stop there and take any questions if anybody has any questions or we can move on to the next talk. Okay, so now what I'd like to do is introduce our first scientific speaker, our keynote speaker. Oh, we have one question, thank you. So regarding the ENCODE future, so what are the NHGRI plan to do? Like what kind of focus or emphasis? Sure, some of this is public record and some of this is to be decided yet. And I can tell you about the public record part. And we've recently accepted applications for a new round of ENCODE. They haven't been reviewed and funding decisions haven't been made. But the applications we accepted were for new mapping centers, sort of like the production centers that we have now. Computational analysis centers, that's an ongoing activity that we have now in ENCODE. And then a new type of activity, functional characterization centers. We also have applications for those in addition to a data coordinating center and a data analysis center. So there's a good chance that moving forward, there'll be more data production and ENCODE, more mapping. There'll be releases of data through the DCC in analysis. And then we might have additional information about a function of different genomic regions. The past iterations of ENCODE did not focus on functional analysis of the mapping results. The thought was that was within the purview of the community. The idea was to do the mapping and to come up with raw material for others to work on. But we've seen that this is a need for us as well to be involved in. So that's why that's come in. Thank you.