We're going to use one of the visualization tool which is called IGV. And I will start with an introduction about visualization for your sequencing data and go over some example of what you want to look at and how to do it. Some objective is to know more about visualization tool, to know when we want to use it. Get more experience with a particular browser, which is going to be IGV, and look at some really detailed examples so you're going to be able to do it at some after for some single nucleotide or structural variant. And it's going to be divided in two parts, about in general some genome browser and an IVG over you. And as I say, detailed example. So visualization tool. Why do we want to visualize our data? Because it's help us. And we can take an example of a known data set which is an unscored question data set. In this data set, you have actually four data, which are here, and both have x and y values. And if you do basic summary statistics, you would find out that your variance for the y value and the x value are actually the same, as well as the variance and the correlation between x and y. And you can start the matrix for quite some time, but you're not going to learn more with basic statistics. But if you actually plot it, it comes across right away as that the four data sets are different, because one is actually mainly linear with some variance. The second one is actually a curve. The third one is a nice linear plot with one alpha here. And the last one has value only on the same value, x value. And our brain is actually very good and very powerful as detecting strong patterns. As an example, so the brain actually, you have two things. You have the pre-attentive versus the attentive visual processing. And the pre-attentive processing is your strong ability to notice what are the difference in shape, color, and the space. So you probably know this book in French with Charlie. In English, it's very well-known, I believe. And I love it as a kid. And as an image on the left, it's a basic one. You can easily spot Charlie. So you're going to use your pre-attentive attention and right away you can see it. So when on the right, you have to actually track this image and figure out where he's on the beach. But so we want to use actually the pre-attentive attention to processing to really spot outliers in our data. And as another example, if the outliers are, if you display it properly, you're going to catch them very easily as on these different examples. So the human visual system is, we could say, a low-cost and high-performance for this type of outlier dissection. And it can be actually more efficient than trying to debug and write a script to find those. But at least for some example, so you know after what you want to detect in your data, and then you can code for it. And we would do that at several steps in your analysis. It can be at the beginning to look at your quality. A few data, it can be at the end when you have your vc file and you want to look at a specific variant or at any steps to check that your output makes sense. And we're going to see some examples. What do you have a visual system tool to use? There are actually many general browsers, more than 40. They're very in function of the task you want to do. What are the type of data they accept you can use with? Some are web-based, some are not. So there is some private data privacy issues. You might not want to upload your cancer sample on a website which is not secure. So actually, for example, you can use it locally. So that's the privacy issue you have solved. And there are some browsers that are specific to different species or pathogens. If you are working on a rare pathogens, you might have a specific browser for that. For group sequencing, several ones. And just these are a few and maybe the most widely used. IGV is the most widely used. And he has the advantage so you can import any kind of sequencing data. And he has the benefit of being able to use data locally and from servers, from cloud servers. UCSC has a browser, the genome browser, which has as well, they created the cancer genome browser. So you can upload some data from public cancer data sets so you would be able to preserve a large number of already published samples. Galaxy, the Tractor, is another one that you can get this link to Galaxy. Haven't used it much, so I can't say much about it. And Servant is another one that is really powerful and he has the benefit of allowing you to visualize the data and as well as doing some analysis. Because I remember in a previous workshop, we were using IGV and someone was telling me, but yes, this is an SNB, but what does it correspond to? Is that, and since I imagine, and is that a non synonymous one? And this IGV is not going to tell you. You have to run a SNPF on the side. But actually, Servant will allow you to perform the analysis at the same time. So we're going to focus on IGV for this lab. And I want to mention that all the slides with the Broad Institute logo on the top right actually slide adapted from the user guide from the Broad for IGV. IGV, you can upload from micro data to an asset to copy number data to whole genome sequencing data in it. And what are the features of IGV? You can explore large genomic data sets in an intuitive, easy to use interface way. And you can integrate different data, so the different sequencing data you have, as well as the clinical data you might have about your sample, which can be the sex of the patient, or if he was a metastatic patient or not, or is my sample the primary or the metastatic sample, and then you can sort according to all these attributes as an example. And you can as well write the basket to make this task automatic. So my colleague had a few hundred variants she wanted to look at. She's not going to do it every single one by hand. So she actually wrote a script to tell IGV, go in this location, take a snapshot, use this parameter to display the read and take a screenshot. And then she could easily after look at all of them so as a sanity check for her variant. So that's something you can do. It's a bit more advanced. We're not going to do it today, but it's possible. IGV can use files that you have locally on your computer, can import and can use data that inside on servers like as a TCGA data set, you can actually load those or you can connect to a server and load data. So it has both a local and remote access, which is important especially for privacy of the data. And as well you don't want to download all the TCGA data set like the cancer data set to locally because it's going to be way too big. So what do we do with IGV as a basis?  You're interested and you can look at for world genome sequencing data we use this morning. You can look at SNVs or structural variants. So on IGV on the website, you can actually start it from the right tab or register and install it locally. And I hope you all have a hit on your computer now. And the standard layout is the following. So you are able to select the genome on the top left. The default I think is still 18, 19, but usually we're changing to 19 because now we're going to that. And then we're going to load your data. So you have the file under the file menu. You can load either your local five or either from the server. And here it's an example, loading some published data from the server, which is some Chipsick data on a histone back. And when you load the data, you have this type of display that appear. So you have every sample has its own track here. You have the name of the sample, the name of your track. You have the genome ruler. And you will be able to zoom in here. It's a full genome, so chromosome 1 to 22 and X and Y. And you're going to be able to zoom in. And you're going to have the ideogram that's going to appear.  And at the bottom, you have the genome feature. By default, it's going to load the RISC gene annotation that you can load some other annotation like Ensembl or UGCNC. And then you would be able inside this panel to go up and down and expand or not. What file format and track can we use a type of track? Basically, the file format defines the track type. So IGV is going to recognize if you load a BAM file, it's going to display it in a particular way because it knows it's a BAM file. And then you can play with the color and the ordering. But it will recognize the BAM file. And there are more than 30 file formats that are actually accepted by IGV. So you can have, of course, the BAM, the BAM file from some particular region. You will be able to load copy numbers and data and that. So our VCF file as well and WIC. So probably the file that's going to be generated you're going to be able to load it. And this is a list of all the format that are accepted by IGV. So when we load our data, this is loading a BAM file, you're going to see that there are actually too much read to please play. You cannot display the whole genome. That's why you're going to have the indication and zooming to see the alignment. But you can first see on top of the tracks they actually show the coverage. So that's how many read pile up at this particular location. So you can see on this sample, the coverage is pretty uniform, except at the center as you expect because of multiple regions that are very hard to align. And then you will need to zoom in to be able to see your reads and how far do you need to zoom in to see the alignment? Roughly 30K, but it really depends off your coverage and how many reads you have in your library. And it's going to be, the more reads you are, the more memory you're going to have to be able to use to be able to display the reads. So it's a balance between how high is your coverage and the memory you're using. So you're just going to play with those parameters. You're going to keep zooming in and end up where you can see your reads. So we're going to zoom in and add some after you. So this is a basic type of figure you're going to see with your BAM file. So every single gray box, it's a read. And you can see the direction of the read by the, because there is an arrow at the end. So this one is a, for example, on the river strand and this one is on the forward strand. It is quite in this way or this way, right? And there are some colors that have here. So basically you, if you read match to the reference synom, there is no matchman. It's going to be gray. However, if you have a mismatch, you're going to be color coded. And so that's what you see as the blue and the orange, for example, here. And IGV displays a quality as well with the transparency. So if it's a dark blue, it's a confidence, you have confidence that it's a good quality base pair. If it's faint, more and more transparent, it's not a good quality one. So that's going to be one of the information you're going to take into account when you're going to look at your SNBs, is that supported by good quality base pairs. The other thing, yeah, it's not on this figure, but if the read doesn't map, the read quality mapping is not very good, it's going to be, the gray is going to be more lighter and lighter up to white. So that means it was, I don't need it yet there, but it was not confident to analyze the read at this position. We're going to see it later. So what are we going to look at when we want to evaluate the validity of our SNBs? We're going to look at the coverage, the amount of support for the SNB, if there are any BAs, PCR, T5, or scan BAs, the mapping quality and the base quality, as I mentioned before. And for structural variants, we're going to look at the coverage insert size and the read pair orientation. So doing some SNEAK and SNB, this is an example of a good quality SNEAKs. As you can see on the first track, the top of the track, you have the number of base pairs that are the reference, as you see here in blue, and the number or the percentage that are the alternate read or T. So here, I think it's 60%, 40%. So it's nearly, but it's probably an heterogeneous SNEAKs. And you can see that all your T are red, nice red color. So most of these base pairs are good quality, so you would confidence that it's a real SNEAK. And actually, it's annotated in the SNEAK you can see at the bottom. Another example of something you might just take that is an artifact is, for example, here. We call all the read by strand. So you can see that all your alternative, all your base C, actually coming from the same strand, like a reverse strand, that's something went wrong. Because none of the forward strands read that map these locations support this SNB. So you would spot it as being suspicious and probably not a true one. Yeah? That would be during the? Yeah, actually, that is a panel at this time. It can, yeah. What about, so that was two examples, and we actually go see more examples in the lab for SNB. What about structural variants? So we're going to use the fact that we have pair reads. And using evaluated the answer side between your two pairs the orientation of your pairs going to help us to detect some structural variant like deletion and session or translocation. So just to visualize a bit more what we do with parent sequencing, you have your DNA and you're going to fragment it. And you're going to select fragment for a particular size. Quite often it's 350 base pairs. So your fragment's going to be on average 350 base pairs, for example. But of course, you're going to have some variation. So that is the answer side, as Matt mentioned this morning. And the one you're going to align to the genome, your pair reads, you're going to be evaluating. If you insert size between where you align it, it corresponds to what you expect. So roughly 250 base pairs in the example I took. However, the inferential side is larger or smaller than what you were expecting. It's going to give you some indications that maybe a deletion and insertion of an integral interchromosomal reaction happened. So if we take the example of a deletion, what is the effect on the insert size? So you have at the top the reference genome and a huge sample at the bottom. And we're going to remove the red parts. It's going to be a deletion of this sequence. So the right and the left parts are going to be together now. And if you sequence this, you're going to have a segment. They're going to be a fragment. They're going to cover this region. And your reads are going to come from here and here. But when you map them to the reference genome, they're going to be a lot further apart, right? So your inferential size is larger than the expected value. And we can color. On IGV, you can color alignment by the insert size. And you will be able to see in this example of a deletion, these red reads that are actually at the border of the deletion. And you can see that the coverage inside the deletion is actually lower than on the two hands of the deletion, but it's not empty. So it's likely a heterogeneous deletion and not an homogeneous deletion. All can be explained by the fact that if we take an example of a cancer sample, a tumor sample, the sample can be not really homogeneous and can have some cells that have the deletion and some cells that doesn't have the deletion. So when you pull, when you sequence all these cells, you would have some reads from the cells that don't have the deletion that will map here. And the ones that have the deletion would not be present. So you would have a difference in coverage. So that's another explanation why you would see that. But so the color code is for an incisor smaller than expected, it's going to be blue. And it's inside larger than I expected, it's going to be red. And if you pair a map on a different chromosome, they're going to be colored with the different color you can see at the bottom of the slide. So if you have a very multi-color samples region, it's probably like a translocation happen. And if you always have the same color, it's actually better because you know that it's going to be a translocation between the chromosome you're looking at and another one which is going to be color-colored here, for example, six. So here I'm taking an example of rearrangements. So here you have on chromosome one some reads are going to be colored with the brown ones, which indicates that so pair it's actually mapping to chromosome six and this versa. And that's another function of IGV. You can actually split your page or your panel into two to be able to look at two locations that are not next to each other. What about with pair orientation? This can reveal structural events such as inversion, duplication, translocation, or even more complex rearrangement. And the orientation is defined in terms of with trans, less versus right, or we don't order first versus second. So we're going to see an example. We take the example of the inversion. So we have the segment A to B that somehow happened to be invested in your sample, as you can see here. So we're going to have fragments that cover the breakpoint B and cover the other breakpoint A. So if we take the example of the breakpoint which is at B here, you're going to have the reads that map to this region come from this region going to be aligned properly on the same region as the reference theorem. However, the reads that come from the inverse region going to map on the same direction close to B inside the inverse region. And for the read pairs that come from the other breakpoint, the right part going to map properly on the right part here, yes. And the second part of the read, so actually for one, going to map here on the same direction. So for an inversion, you're going to see this pattern. You're going to see some reads that point in the same direction as a way. And it's something you don't expect because you really should be like this. And they're going to be color coded as turquoise or dark blue for the left direction and the right direction. So on IGV, you will be able to color by pair orientation. And an inversion, a good inversion is going to look like this. When at each breakpoint, you're going to see this turquoise and blue pairs reads since the pair are like this. And so IGV has on this website a table showing what are the different events that can happen and how it's color coded. So the normal one is this one. Then we saw the tilt and the blue and the green with the translocation ones that it posts like this. All right. Do you have any questions? Yes. I see you have a big name. So just for one file, you have a lot of data. How would you go through this and try to splice this information, say for inversions, instead of looking at what you have to write? You would do it tomorrow in the lab. We have a LMP. So you have turquoise that actually looks at the adetic structural events. And when you have a list of events, you would actually go in IGV and check if they looks good or not. You would not browse all your samples randomly. You can do that at the beginning just to be sure that your data seems the right quality and you don't spot very strong artifact. But then usually you have a particular location that you find it using all the tools before. And then you're going to go and look at it.


Chapter two, beginning at verse one, it came to pass in those days that a decree went out from Caesar Augustus that all the world should be registered. This census first took place while Quirinius was governing Syria. So all went to be registered, everyone to his own city. Joseph also went up from Galilee out of the city of Nazareth into Judea, to the city of David, which is called Bethlehem, because he was of the house and lineage of David. To be registered with Mary is betrothed wife, who was with child. We'll stop there and begin our study. You know, when my children were small, we wanted to teach them the significance of Christmas. I don't know if we succeeded or not, but we sure tried. We wanted to awaken them to the fact that Christmas is a celebration concerning the birth of a savior. And we know that children enjoy their presence in all and we wanted to give them presence and we wanted them to enjoy that, to be able to unwrap and enjoy present. But the first thing we wanted to teach them was the significance of Christmas because we had seen the commercialization over the years and wanted to do our best to help them to know that there's something greater than receiving a gift under a tree. And so what we would do with them is we would read this story. And so that's basically what we're doing this morning, just remembering, just going through the word to remind ourselves concerning what it means to be Christians and why we celebrate this time that is referred to as Christmas. As we look at this passage here, we need to put it in context. For over 400 years, God had been silent towards the nation of Israel. The last book of the Old Testament is a book of Malachi. And Malachi was a prophet who ministered in a time when Israel had become terribly corrupt. Israel's religion had been overtaken by outward religious practices. And the result was that the people had become callous. They'd become hard hearted. And the priests had tired of serving the Lord. Corruption had entered into their religious system. So as that was taking place, God raised up a prophet. His name was Malachi. And when you look at the book of Malachi, you'll see that the message that God gave to him was one of rebuke. It was one of a call for repentance, a calling back to God. Because the time of Malachi was drastic. It was a bad time, so drastic measures needed to be taken. A strong message had to be given. When you look at the book of Malachi, you'll see that the people were led by ungodly compromising priests. They were making worthless offerings to God. They were divorcing their wives to marry heathens. They were living in a false sense of security. They believed themselves to be living lives that actually were pleasing to God. When you read the book, you'll see the argument that goes on between the people and their God. So Malachi was sent to bring a message, but these people would not repent. They wouldn't respond to the message that he brought them. They were so lacking in fear of God. They were so devoid of spiritual discernment that even when their deeds were pointed out, they still could see no harm in what they were doing and they never repented. And because the people of Israel, during that day, 400 years before Christ would not repent, God remained silent. God stopped speaking to them. So Malachi is the last book of the Old Testament and from Malachi to the New Testament, they refer to it, theologians refer to it as 400 years of silence. Now God is about to break his silence. God is about to keep his promise to his people. God had made a promise. He had stated in the book of Micah, he had stated that the Messiah would be born in a small village called Bethlehem. In Micah chapter five verse two, it says, you Bethlehem ifroth, though you are little among the thousands of Judah, yet out of you shall come forth to me the one to be ruler in Israel whose goings forth are from of old, from everlasting. So God had promised 700 years before through Micah that Messiah would come and he would be born in a place called Bethlehem. But the question is, how can a resident of Nazareth be provoked to go south to a place called Bethlehem? The answer is God moved a petty ruler to order a census. That's what it says in chapter two verse one and two where it says it came to pass in those days that a decree went out from Caesar Augustus that all the world should be registered. The census first took place while Quirinias was governing Syria. God moved him and he made an order that people were to return to their villages to partake in the census. In Proverbs 21 verse one, the writer says the king's heart is in the hand of the Lord like the rivers of water. He turns it wherever he wishes. And so God moved Caesar Augustus and he issued a decree that all the Roman world would be registered. He ordered a census. And so as this takes place, it says in verse three, all went to be registered, everyone to his own city. Joseph also went up from Galilee out of the city of Nazareth into Judea to the city of David which is called Bethlehem because he was of the house and lineage of David to be registered with Mary his betrothed wife who was with child. So Mary's espouse husband Joseph was a descendant of King David. King David had been born in Bethlehem a thousand years earlier and the Jews kept track of their genealogies. So Joseph knew he needed to go to the city of Bethlehem. Now by law, Mary didn't have to go but she went with him anyway. There were several reasons why she would take that trip. One was her time was close at hand. Joseph wouldn't want to leave her. Second, he wouldn't want to leave her alone because he knew how she'd be treated by the people there in the village. And third, it may be that Joseph knew that Jesus was to be born in Bethlehem. And so they make their trip. It says in verse six, so it was that while they were there, the days were completed for her to be delivered and she brought forth her firstborn son, wrapped him in swaddling cloths, laid him in a manger because there was no room for them in the inn. In spite of the fact that Mary was obviously pregnant, nobody would give up their room for her. So they were forced to lodge outside. Notice in verse seven how it says she brought forth her firstborn son, wrapped him in swaddling cloths. When you look at that, let me give you a couple of insights into this. Firstborn, firstborn has at least two applications. One, firstborn would be obvious, he's the first child that she gave birth to. You know in scripture that she had other children, sons and daughters, but he was the firstborn. In Matthew 13 verses 55 and 56, Jesus's brothers are named. The question is asked, is this not the carpenter's son? Is not his mother called Mary and his brothers, James, Josie, Simon, and Judas, and his sisters? Are they not all with us? Where then did this man get these things? So when it speaks of firstborn, it would be speaking one in terms of just the fact that he was the first of her children. But secondly, it would speak of his preeminence. It gives us insight into his greatness. It gives us insight into his glory because Colossians 1.15, speaking of Jesus, says he is the image of the invisible God, the firstborn over all creation. He has preeminence and he has prominence. And what does she do? Verse seven says she wrapped him in swaddling cloths and she laid him in a manger. Swaddling cloths were wrapped around the baby so the baby looked like a little burrito. That's how they would wrap him up. And it became his clothing for a year. But she laid him, notice, in a manger. And manger is where the animals would feed. Why would that be significant? Well, that reveals to us the humility of our God. In 2 Corinthians 8, verse nine, it says you know the grace of our Lord Jesus Christ that though he was rich, yet for your sakes he became poor, that you through his poverty might become rich. You would have thought that he would have been placed in a palace, but instead he was placed in a manger. Somebody once said he was placed in a manger that people who act like beasts might have the bread of life. It says also in verse seven, there was no room for them in the inn. When you look at the word inn in the original language, there are actually two words that are translated by the single word inn. One of the words really speaks of what would be called a hotel or a hostel. But the other speaks of an enclosure, an enclosure that was used for the care of animals. This particular inn had no water, rather it had water but no host. There was no food or ordinary comforts that were supplied. It wasn't a hotel with a stable outside, it was like a stable. It says that there wasn't room for Mary even in basically a stable. So Mary gave birth to Jesus in the place that was used for the care of the sheep. We're gonna look at that in just a moment. So as all of this is taking place, verse eight. Now there were in the same country shepherds living out in the fields, keeping watch over their flock by night. Behold an angel of the Lord stood before them. The glory of the Lord shone around them. They were greatly afraid. And the angel said to them, boo, now he didn't. The angel said to them, do not be afraid. For behold, I bring you good tidings and great joy which will be to all people. For there is born to you this day in the city of David a savior who is Christ the Lord. And this will be the sign to you. You will find a babe wrapped in swaddling cloths lying in a manger. Suddenly there was with the angel a multitude of the heavenly host praising God and saying glory to God in the highest and on earth peace, goodwill toward men. These shepherds. When you look at shepherds in the history of Israel very often the shepherds were disrespected. Part of the reason why the shepherds were disrespected is because their duties kept them from observing the law. They weren't able to be observant. What is today you go to Israel they'll refer to you to Jews as observant Jews. They weren't able to observe the law. And so they were disrespected because of that. They were also not schooled in the law and therefore were considered ignorant. But what this gives to us is an insight that God made his son available to any who might come to him. Any who might desire him. In 1 Corinthians 1, 26 through 29 Paul said it like this. He said, brothers think of what you were when you were called. Not many of you were wise by human standards. Not many were influential. Not many were of noble birth. But God chose the foolish things of the world to shame the wise. God chose the weak things of the world to shame the strong. He chose the lowly things of this world and the despised things, the things that are not to nullify the things that are so that no one may boast before him. God reached out and he spoke to these and touched these people through the angelic visitation. These shepherds out in the field were undoubtedly keeping the sheep that would be used for temple sacrifices. And in the ordinary event of their life an extraordinary thing occurred. I've discovered in some of you that God has a way of interrupting the ordinary events of our lives in order to do something extraordinary. He has a way of doing that. I don't know what you were doing before you got saved. I don't know what your life was like before you got saved. Mine was just simply an ordinary life and God has a way of interrupting ordinary events in our life to break through and to awaken us to our need for him. And that's what's taking place here. They were on the job doing what they normally do. When suddenly the light just shines brightly about them there's an angel of the Lord above them and they see the glory of the Lord and God's glory is revealed. His glory becomes visible to them in the way that it had when Moses had his encounter with God at that burning bush. His glory was revealed as it had to the Jews when they were in the wilderness and he went before them in a pillar of fire. It was revealed to them as it had been to their fathers when he revealed his glory in the temple and they saw what was called the Shekinah glory of God. And I say see this glory their hearts are trembling in fear. You know they had heard of the things that had taken place in the past. They knew of angels that visited the leaders like Abraham and Gideon and Daniel but now an angel is standing before them and the natural response notice with me as they feared for their lives and as they're afraid their verse 10 says do not be afraid or bring you good tidings of great joy which will be to all people. So the angel commands them do not be afraid even though it's natural for them to be. Their fear is going to be changed into joy because the hope of the ages has been fulfilled. Messiah has been born in verse 11 there is born to you this day in the city of David a savior who is Christ the Lord. This day he's saying signals a new day. Dawn has broken spiritually. Man has been living in darkness but the darkness is being driven away by the light. In Isaiah 9 verse 2 it says the people who walked in darkness have seen a great light. Those who dwelt in the land of the shadow of death upon them a light has shined. He says in verses 11 and 12 there's been born a savior one who's going to confront all the sin of the world. There's been born to you the one who will one day conquer Satan the one who will one day rule. In Colossians 2.15 it says having disarmed the powers and authorities he made a public spectacle of them triumphing over them by the cross. Revelation 19.16 identifies Jesus as king of kings and the Lord of lords. And the angel states very clearly he's the savior. He is Christ the Lord. He had told Joseph call his name Jesus.  Messiah will save and he'll save any who believe both you and the Gentile. Isaiah 52.10 says the Lord has made bare his holy arm in the eyes of all nations and all the ends of the earth shall see the salvation of our God. He said he is Christ he is the Lord. He is Christ the anointed one. The prophets and kings and priests would be anointed with oil when installed into their offices, but he's also the Lord because it's at the name of Jesus that every knee shall bow and every tongue shall confess that he is Lord. And he says in verse 12, this will be the sign to you. You will find a babe wrapped in swaddling cloth lying in a manger. I wanna talk to you about that for just a moment. Lying in a manger. The shepherds were in the field carrying for the sheep but there was an enclosure that would be used. That would be used to actually, it would be the place where certain sacrificial sheep as well as the scapegoat and the sacrificial goat would be kept. These goats would be used in what was called the day of atonement. When you consider that Jesus was placed in a manger where the sheep, the sheep that were sacrificed as well as the goats, it gives you some insight because in the sacrificial system of Israel, during Yom Kippur, the day of atonement, the priest would lay his hands on one of the sheep, they would end up sacrificing, the blood would be spilled, he'd be a blood offering. But the other one would receive also a laying hand on of hands and he would be driven into the wilderness symbolically taking the sins of the people away. So you have in this particular enclosure, you have these goats, but you also have the sacrificial sheep. And when you consider that Jesus Christ was born in a place that housed the sacrifice, it gives you greater insight into the knowledge of what Jesus Christ came to do. Jesus Christ came to be sacrificed in order that he might take away the sin of the people. That's why John the Baptist would say concerning Christ, behold the Lamb of God who taken away the sin of the world. So the sin of mankind would be placed on this one who was to be offered as sacrifice. And so it's symbolic and it's revelatory to us in that the people came into an area, Jesus was placed in an area where the sacrificial sheep were raised, where the goat that was the scapegoat in the sacrificial goat would be. And it gives us insight into Jesus Christ coming in order to be that offering to God. So he was born for us to be savior of the world. And for me that's a very important thing to never forget because especially here in the United States, we the church are to be the conscience of the nation and we're to preach a message that speaks to the nation to remind the nation and to remind all people who don't know the Lord that Christmas is much more than just a time of celebration for us to enjoy with our families. It's a great time to be with my family. It's nice to have a meal with them and it's nice to be able to see the joy as they open the gifts that they've received and all of that's good, there's nothing wrong with that. But for me, especially today in these last days that we're living in, it is of much more import for us to make sure that we the church don't forget why we celebrate. That's why I'm blessed you're here. I really am, that's why I'm blessed you're here.  Jesus Christ's birth was intended to bring mega-carous, great joy to all people. Why? Because a savior had been born. You see, the gospel message is a message that is not intended to simply appeal to man's intellect. The gospel message is a message that is not simply given in order that people might hear words and begin to think concerning the things related to what's being said as if it's a historical narrative of some sort. The gospel message has been given to us because it's a message that is moral, it is moral in its message and it is intended to speak to man's conscience. Man who had been living in darkness, the word darkness there doesn't simply speak concerning of being dark-conditioned where there's no sun shining. It's speaking of the moral darkness. And man who had been in darkness, those who lived in the shadow of darkness, those who are in the darkness, those are the ones that the great light has shined upon. That's the whole point. When the gospel message is preached, it's not intended to simply cause people to have an intellectual conversation with the word of God. The gospel message is intended to speak to the conscience and heart of man. So that awakens in us a sense within us of a lostness, a sense of a spiritual darkness, a sense of need, something that you know you need but you cannot put your finger on it. It's kind of like when my mom, sometimes when I was growing up, my mom would say to me, she'd say, I have hunger for something but I don't know what it is. She'd say, I've got something and she used to kind of smack her lips. She'd go, you know what I mean? Have you ever been hungry for something but you really don't know what it is? My mom would say that when in reality what I had, all my life was the same kind of thing spiritually. There was something inside of me. I have a hunger for something but I don't know what it is. And it isn't simply so that I might be happy because I knew even as a kid that happiness is fleeting. Happiness is related to happenings. It's my circumstances. So something good may occur and therefore I'm happy. I needed something deeper than that. I needed something that was deeper than just the happiness that I could experience because certain things are going right. I needed joy. I needed something that would be deep within my soul. Something that whenever I'd go through a pain or sorrow or hurt of some sort that I could go to the well of joy and it could spring up within me and I could say it's all gonna be all, it's good because there's something better than this and that comes from Christ and that's why, amen. And that's why the Bible says that there'll be mega-carous. There'll be great joy in your life. Great joy. See that's what I wanted my kids to know. That there's something deeper. There's something better. I mean, as a kid I loved the gifts and toys when we'd get them on occasion. You know, I enjoyed it. The bicycle my dad bought me or whatever I liked. That of course I did. But every one of us know that the things that we have perish with the using. We know that. We know that you can do all that you want. You can save up for as long as you want. You can get what it was. And there's nothing wrong with that. But once you get it, you say there's got to be something else. But do you know that when I came to faith in Christ I never said there's got to be something else? Because I found what there is. It's him. I don't need something else. I don't need something else. That's a fact. I'm just telling you the truth. I don't need something else. I didn't come to faith in Christ in desire to hear what Mohammed had to say. I didn't come to faith in Christ and wonder what the Buddhists believe. I came to Christ and my soul was satisfied. My thirst was quenched. My hunger was filled. That's what happens when you have a real relationship with Jesus Christ.  It's their favorite word for us.  The person who believes in Christ and fails but still believes and tries or the person who doesn't believe in Christ but celebrates Christmas.  Who's the hypocrite? It doesn't make sense to me. It never has. I mean, if you don't believe in Christ, then don't give gifts. If you don't believe in Christ, then don't go to parties. If you don't believe in Christ, just stay at home. What's the point? What's the point? See, but for those of us who love the Lord, it's an amazing time because we get to celebrate the birth of our Savior. We get a chance to share once again to a world that's in darkness that the light has sprung and that the Lord Jesus Christ has come for us. He is the Lamb of God who takes away the sin of the world. And no wonder, as this is being spoken, it says in verse 13, there was with the angel a multitude of the heavenly hosts praising God and saying, glory to God in the highest and on earth peace, goodwill toward men. In a moment of time, we see something that changes lives. You see, there is no peace on earth except among those with whom God is well pleased. The Bible says it very clearly. Men are in a state of hostility. They're in opposition to heaven and they're in opposition to one another. But God has provided a way of peace and he did it through his son, Jesus Christ. You see, when men become reconciled to God through the Son, they're gonna learn to love one another. Goodwill will dwell among them. Goodwill will speak in them. Goodwill will speak through them. And goodwill will work through them. And peace comes. When you're reconciled to God, the Bible makes it very clear that there is a cosmic war between man and God. God is sent to man in terms of peace. It's called the message of the gospel. It is calling on God's part to man for an unconditional surrender. We're not gonna have a treaty that's made where both parties say, I was wrong, I was wrong, let's get along. The gospel message is called the message of reconciliation because God is sending terms of peace to man, but they're unconditional terms saying, I am victorious, you have lost, I'm calling you to peace with me, recognize your lostness and ask for forgiveness. That comes to the gospel. And so when you come to faith in Christ, you don't come saying, well, I'm guilty with an explanation. You come before the Lord and you say, I am a sinner and I'm in need of grace and I'm in need of forgiveness. I have no excuse. I can't blame anybody anymore.   My circumstances, my race, my education are lack thereof. I'm a sinner in need of your grace and forgiveness. And I ask in the name of Jesus, the savior of the world, I ask that you would forgive me. And God does that. See, so glory to God in the highest and on earth peace, goodwill towards men. I'm gonna close by jumping ahead to verse 19 and 20 and I wanna show you something and we'll close. As all of this takes place and they find Mary and Joseph, they see the baby in a manger and they begin to make known the things that have happened. It says in verse 18, I'll start with verse 18, all those who heard it marveled at those things which were told them by the shepherds. They were the first evangelists, if you will. But Mary kept all these things and pondered them in her heart. Mary pondered these things. Mary thought of what she had been told by the angel at the annunciation. Mary thought of how Joseph shared what he had been told by the angel. Mary pondered how the shepherds were overwhelmed by the angels and considered the response of the people who only wondered at the strange story. And she thought, what will this lead to? The birth of the child, what will this lead to? She thought, she kept all these things and pondered them in her heart. What will this lead to? This amazing moment where this girl, she was probably about 14 years old, gave birth alone, carried her child alone, placed a child in a manger, all of that. This 14 year old girl, and she's thinking, what will this lead to? In verse 34 of the same chapter, it says, Simeon blessed them and said to Mary, his mother, behold, this child is destined for the fall and rising of many in Israel, for a sign which will be spoken against, yes, a sword will pierce through your own soul also, that the thoughts of many hearts may be revealed. What will this lead to? Being placed in a manger leads to being placed on a cross. Being placed on a cross leads to being placed in a tomb. What is this going to lead to? What do you think about Mary? That one day this blessed son will be beaten, tortured and crucified. A sword will pierce through your own soul.  A sword will pierce your own soul, Mary. You gave birth to the one who can give you new birth.  The one that you birthed will be the one who saves you. And when you see this take place, you're going to see the cost of joy, because joy came at a cost. That's why we don't take Christmas for granted because Christmas finds its summation in Easter. We don't take it for granted. We don't just party on Christmas. We don't just give gifts and complain that we didn't get enough ourselves. We don't simply overeat and kind of ignore what the day means. Thank you for being here with us today to remember who Jesus is. Thank you. Thank you for your heart for Christ, your desire to know him and to worship him. May we never forget what he's done for us. For the savior of the world was born Christmas day. Our savior.


was like putting a lot of events like this is really fun and like most of all it's great so great little guy oh yeah it gets like me new people got some sweet rides right here I ate a piece of pizza on that ride that was pretty fun


Monday morning, President Joe Biden and First Lady Jill Biden flew into Westlake's Bluegrass Airport where they will be meeting Governor Andy Beshear and First Lady Brittany Beshear to view flood damage in Eastern Kentucky. And I promise you, we're staying in the federal government along with the state and county in the city. We're staying until everybody's back to where they were, not a joke. In response to catastrophic flooding that left 37 Eastern Kentuckians dead, hundreds displaced and countless homes destroyed, President Joe Biden and First Lady Jill Biden arrived at Westlake's Bluegrass Airport to view flooding damage in Eastern Kentucky. During Biden's visit, he spoke with state and local officials about the damage. Less than two weeks ago, this region suffered the most devastating, destructive flooding to hit our commonwealth in my lifetime. At least 37, now I believe 38 lives were lost, including four young children. Communities have been destroyed, if not completely wiped off the map. Once again, our people are hurting, facing loss and hardship on a scale that's hard to process. Eastern Kentucky is a place where flooding is a part of life, but no one has ever seen anything like the historic flooding that hit us on the night of July 26th. It's all in our hands, this life of time that's given to us all. It is all in our hands, it is all in our hands. Experienced heart specialists and sub-specialists collaborating for the benefit of your care. Top 10% national hospital rankings for patient safety and heart attack and heart failure treatment. The technology is skilled to perform extraordinary, complex, minimally invasive cardiac, electrophysiology, interventional and structural heart surgeries. This is a heart and vascular institute at Pikeville Medical Center. It is all in our hands, it is all in our hands. When it comes to your heart, place your care in our hands, it is all in our hands. During Bashir's comments, he commended volunteers, first responders, and community members who helped each other out in a time of need. We've also once again seen the professionalism and outright heroism of the Kentucky National Guard, Kentucky State Police, Fish and Wildlife Personnel, Kentucky Emergency Management and local first responders who showed up just not from here, but from all over the Lexington Fire Department trying to get to hazard, couldn't get through it. So they did over 60 rescues when they first hit water right here in Brethwick County. Mr. President, our Kentucky National Guard is the greatest guard in the country. Its members remind us that they are us. They are Kentuckians who are our neighbors, who in incredible times get called to service and they never let us down. But for every rescue of our first responders, there were two by community members, neighbors that may have had a kayak. There was a young man in Letcher County with a jet ski, but I'm not kidding, you rescue more than 10 people, thankfully having that in his garage, risking their lives to help one another. Stories of neighbors rushing from their own flooded homes to their neighbors, and let me tell you, I remember watching a cleanup talking to somebody pulling stuff out, saying is this your house? She said, no, mine's two down, but we're going to finish this one before we get to mine. And we've seen so many outstanding young Kentuckians stepping up. It looks like one may have even given his life in the service of others. We have seen a remarkable response because we Kentuckians are remarkable people. Following Governor Beshear, President Biden mentioned efforts of a $1.2 billion infrastructure bill that would help Kentuckians to utilities and services such as high speed internet following the flooding. What we're going to do is we're going to see, for example, if they got to put a new waterline in the community, there's no reason why they can't at the same time be digging a line that puts in a whole new modern line for internet connections. Why? Why can't we do that? So it's going to be different. We're going to come back better than before. For Mountain Top News, I'm Joel Korgel.


IIT Bombay, I am so happy that I can meet so many, I think in those days we used to call them pen friends, today we can call them email friends because so many of the colleges from across India are connected with us. So Professor Nagapan and Mr Biju Varghese, so many we have met, very, very happy. I will be very brief. You have already got the link that happened first, the URL. You also have in your Akash booklet a whole section on how, what you can do. Now the whole philosophy of Akash is a device where you have educational content. One such educational content is software. What type of software? Of course, open source software. This is what the project is all about. These are the software offered and the list is growing very rapidly. I am sure all of you are aware of all of these software and the wonderful things that they can do. So now, what is really going to happen? These software, some of you may already be having, you may be using, you may be interested in learning, you may be interested in teaching to your students so that they can use them as tools. This is where this audio visual tool or technique which is basically the spoken tutorial CD or video it will help along with an instruction sheet. It helps in training you very quickly. Now what else do we think when we talk Akash? We talk about as Professor Fatak said, minimal class or lab time, contact time. So what are Akash purposes? Classroom teaching as part of the curriculum of your UG and PG courses you can be used and we would really encourage you to write to us on how, for example, SILAB is being used in various electrical or mechanical engineering courses or mathematics courses. If PHP is very much part of your IT curriculum and so on and so forth, the other aspect is to just have 8 to 10 hours where all of these software can be learnt via the CD. For final year projects that was another object given in as part of the Akash object, you can use this software, you can use, you would have learnt it very quickly because of the learning, self-learning technique and you can use it. And some of you or you know who may be involved in educational technology or the social and educational fields, now that this has been out there into the space, so to say, into the system, into our country for about a couple years or so, we would like to know what is happening, how are people using the software, how are people using the CDs, what is the buzz and definitely that can merit a topic for a final year project too. Fixed minimal learning that is minimum contact time in your class or lab and what better showcase or ambassador than the spoken tutorial video, we are talking about initially only once, one and a half hours to two hours contact time, after that you take home the content on your pen drive or on your laptop and so on, learn and revise and now, how do you know that the learning is complete, okay, you have all the content, fantastic. You have the learning will be complete, your so called initial mastery will be complete, if you want to test that, you just have to contact us, take a simple online assessment test that will force students, teachers, learners to go through the, to revise for the, you know, revise the tutorial and so on, you know like only because of an exam we end up studying our courses, basically that is it, finally in Akash, content of select software can be preloaded, we heard all this wonderful news, computation in Python, SyLab, C C++, hugely capable in only the Akash tablet, not any other tablet, that is pretty awesome, content can be accessed via a link, so you will be having that internet, you can copy it, learn from, you can convert it into an attractive CD for distribution and so on and so forth, imagine the mobility, the flexibility that Akash has and all of this put to use because of that, all of you here sitting in this room, your support, your role, what can you do, spread the awareness, promote spoken tutorials in colleges, schools and office, we are a 15 member team and we have people from, I mean we have each team looking after one or two states and they are very enthusiastic and we collect targets, you know, number of colleges, number of workshops, the way a multinational company or a consumer goods company would develop their market, so we are like that, but we are on a mission, we are working for the government of India for our great country, nothing less, so in this mission you have to be our friends and partners, many of you already are, spread the awareness, not just colleges, schools, government offices, private offices, small and medium enterprises, coordinate with existing field coordinators, we are proud to say we have a promoter, a field coordinator in every state, coordinate with him or her, go and meet him, say hello, network, share your networks, your contacts, your leads and jointly wherever you are promoting Akash, promote spoken tutorials, thank you and in advance, happy Diwali to everybody.


The great conjunction of the planets took place on the winter solstice this year when Saturn and Jupiter aligned directly with the Earth. The result of this phenomena was a spectacular vantage viewing opportunity from the Earth and this event was widely regarded as significant in many aspects of our culture with religious scholars relating the conjunction to the star of Bethlehem visible to observers around the time of Christ's birth and also a footnote among catastrophists that the gravitational influence may trigger a powerful solar flare. But the event passed off into history, leaving Earth-based observers in awe at the spectacular site that was posted into our astronomy club on Facebook. Jupiter and Saturn passed a tenth of a degree from each other in what is known as a great conjunction. Although the two planets passed each other on the sky every 20 years, this was the closest pass in nearly four centuries and the most significant since the year 1226. Both giant planets were visible in a single frame, but also Jupiter's fourth largest moons, Callisto, Ganymede, Io, and Europa were visible along with and Saturn's largest moon, Titan. Other imagery from the large telescope in Chile captured Jupiter's great red spot, but we will leave you with a few moments to ponder this magnificent image of the heavens and you guys let us know what you think of the event and as always, thank you for watching.