There's so many things we need to do with these genome-wide association studies where I think we need much more input from epidemiological scientists. So an overview of what I'm going to do is talk a little bit about some of the nitty-gritty decisions that you need to make on thresholds of all types as you think about how to choose the SNPs that you carry forward. I'll talk a little bit about primary analyses beyond the SNPs genotyped on your platforms as a way of figuring out which SNPs to carry forward and additional information to consider in choosing the SNPs. This was alluded to on one of the early slides that the paper in Nature that Teri was involved with talked about, so publication level information, bioinformatics approaches, pathway studies and so forth. So let's talk a little bit about these nitty-gritty decisions. You heard a lot from Elizabeth and from Laura about these data filters, and I think Gemma Stella will talk a little bit about filtered and unfiltered data, the quality flags that you might set up. So some people prefer actually to start out with basically unfiltered data and carry things through using quality flags, you know, for a lot of different metrics, the Hardy-Wineberg equilibrium flags, the genotyping quality flags and so forth. So you could, you know, you can filter in a number of different ways. Some people don't even want to look at markers with relatively low minor allele frequencies because those are very frequently associated with high P values that don't replicate well in studies.  So, as I said, thresholds before or flags after analysis. Using the quality flags, you know, it has the advantage of preserving fleas, that's what we call them, and sometimes the kinds that you get when you lay down with dogs. These are funny looking signals. And as Debbie Nickerson alluded to earlier, the copy number variations were basically discovered as these fleas on, you know, what looked like otherwise good dogs. And the point is, some of these may be telling us about very important parts of the genome that could be related to our phenotypes of interest. And so, you know, some groups prefer to just use the quality flags. And underappreciated challenge of the different choices that groups make is, so as Laura alluded to, a lot of emphasis now is being put on the possibility of combining data sets, even pre-publication. And so, you know, as people go to share these really big data sets, you have to keep in mind, did people filter prior to analysis, and so, you know, sort of their list of signals is a relatively pure one, or did they just use relatively unfiltered data and set quality flags, in which case you have to pay attention to the quality flags as you try to combine the data. And so, people need to be much more aware of this, I think, going forward as these data sets start to build, and groups make different choices about sort of where they filter and where they flag. When we talk about follow-up studies and optimal designs, I mean, the bottom line is that there are just very practical constraints, a lot of times, on what you can do for follow-up. You know, for relatively rarer diseases and phenotypes, people may put every single case, you know, that they've been able to put together from the world's data into a first-stage analysis, because they feel like they need the maximum power. So, you know, you have then different types of follow-up that you can do. Alternatively, you know, for very common diseases, we talked about type 1 diabetes, type 2 diabetes, various forms of cancer that are quite common in the populations, clearly you can put, you know, what's going to go into the first-stage studies are just a very small subset of the individuals who would potentially be available for being studied. So, then you've got a real tension in terms of what you can afford to do in follow-up. So, sometimes these follow-ups are limited by cost. You may be competing voraciously to get that first publication out. So, sometimes the follow-up studies are going to be limited by time, by the number of samples you have available. And the follow-up studies may be very different when you're talking about copy number variations than when you're talking about SNPs, because following up signals from what may be copy number variation may entail a completely different kind of follow-up. I think you'll start to see arguments that things like one of the approaches I'm going to talk about for looking at untyped alleles, this TUNA approach, or the imputation approaches that Laura's talked about, certainly reduce and may have ultimately eliminate the need for follow-up of additional SNPs within the same samples that you included in the original study. That is, you know, for common variations in the genome, as you get upwards of a million SNPs, between what you're directly type and what you can indirectly interrogate using imputation or these other statistical approaches, you're basically testing everything in that primary sample. So, you're getting all of the common variation. You may then, you know, choose other SNPs to type in follow-up samples, other samples, but you may not need to type much else in your original sample. That may not be true with copy number variation where you get, you know, sometimes direct hits for copy number variants that haven't been described before, and you really need validation of that before you can, you know, fully characterize it. And even the types of follow-up studies you would do for known copy number variants use different technologies. So, that's another thing to consider. The number of SNPs that you carry forward can be something that's predetermined. You may be planning to do an Illumina bundle, for example. So, you'll have 1,536 SNPs that you're going to follow up, and that's it. And then you're faced with, well, how do I choose the 1,536 SNPs that I'm going to follow up? Alternatively, you may design your follow-up study based on thresholds that you predetermined for p-values or false discovery rates, or you may decide after you look at your results what merits follow-up. And, you know, I'm of the belief that let 1,000 flowers bloom. There are lots of scientifically justifiable strategies here, but these are the things that you need to be thinking about and considering the designs of the studies. The primary analysis beyond the direct tests you do, so I'm going to talk a little bit about a different approach for testing untyped alleles. This I call Tuna Nikolai, because Dan Nikolai developed the approach. I think of it as a nice Romanian dish where the key ingredients are a multi-locust measure of linkage disequilibrium and the availability of a reference sample like the HapMap. So, Laura talked about this a little bit indirectly, but the idea with these imputation approaches or what we call Tuna, testing untyped alleles, is the fact that in the HapMap, so we have these reference samples, and we have some set of SNPs that have been genotypes. So here I show three SNPs that we'll say have been directly genotyped on our platform. We've got a test SNP that we know about because it exists in HapMap. And in fact, if we look at our HapMap samples, so this is, we've got these biolithic polymorphisms, we see that given these three SNPs on our platform, the test SNP can be completely determined by the combination of the three SNPs, that is, the genotypes are easily determined because the zero allele at our test SNP is found only on this one haplotype, and the one allele is found on all other haplotypes. Knowing that information allows you with high statistical certainty to assign the alleles and genotypes in individuals that are outside this reference sample for our test polymorphism simply by having used these polymorphisms that are on our platform. And the advantages of these kinds of approaches, you utilize existing information on linkage disequilibrium using something like the reference samples, but you don't have the arbitrary block definitions. You can still construct basically one degree of freedom tests for each known variant with your deciding on the specified uniqueness that you want to go after. As we discussed, the in silico comparisons do require some kind of biological validation. And of course, with these approaches you can't capture information you don't know about. So with these direct approaches, you're limited to the variation that's known in the HATMAP, although the Marconi and Donnelly approach actually does extend to the consideration of each nucleotide as it were as a possible site for variation that you don't know about. So something like Tuna, these testing of untyped alleles, you can use it for in silico follow-up. So you could set a low threshold and tune a type every snip in the vicinity. You can convert lower density screens to higher density. And as Laura mentioned, these are really useful for enabling comparisons of studies across disparate platforms. So basically the way this works, you start out with your set of snips that are directly genotyped. And then for every other snip that you know about in your reference sample, you determine whether that snip provides sufficiently unique information to merit interrogation. If it does, you look for, so that implies that there's no or little pairwise linkage disequilibrium with something you've already typed. So something R squared less than some threshold that you set. Here I put .7. And then you can use multi locus haplotypes to try to impute the genotypes, as they actually do that. Or with Tuna, you're basically just estimating the allele frequencies. And so we find the smallest subset of snips able to interrogate the genotypes with sufficient accuracy. So we're looking again at these multi locus R squared values. The nice thing about Tuna is your primary template needs to be derived only once for each high throughput snip set. So aphymetrics 500k would need to be derived only once, theoretically. But it's so fast to do this, you may choose to optimize it for each project with the set of snips that are actually passing your QC. With this approach, the Tuna approach where we're not really trying to impute individual genotypes, but rather to estimate the frequencies of the untyped alleles, this is a few hours of computer work on a very modest size cluster, so a 10-processor Linux cluster, the kind that we have in our own lab as opposed to the bioinformatics cluster that we use for really serious crunching. So this is the kind of thing, as I say, so it's basically an overnight job to impute or I should say to test all of the polymorphisms in the HATMAP given any platform. And you get substantial return on that kind of investment, so even with the aphymetrics 100k set, you start out, say, in the CEP or your Rubin samples with about 95,000, they're actually polymorphic in the set of phase two HATMAP samples that pass all the HATMAP QC filters that we set up. And so you start out with 95,000. You get a lot of snips for free, remember, because a lot of the snips in the genome are in high pairwise LD with snips on your platform. But you can interrogate an additional couple hundred thousand snips in the Europeans and somewhat less in the Asian or African samples in the HATMAP so that you've got, there's only about 1.4 to 2 million snips that you don't interrogate even using the 100k set. If you go to something a higher throughput platform, you do much better. So with the aphymetrics 500k set, you know, you're getting 1.4 million snips for free, that is in high pairwise linkage disequilibrium with snips that you've already typed. But you can interrogate an additional couple hundred thousand almost so that what's left is only about 500,000 snips, and these are really from the rare end of the frequency spectrum. So once, so it's possible with the high, you know, even this medium throughput platform to get really all of the common variation and what's left is from the very rare end of the minor allele frequency spectrum. Same is true for the Illumina 317k platform. So you get a lot that comes for free because the Illumina platforms were designed knowing about the linkage disequilibrium. You're able to pull in another, you know, 256,000 snips using multi locus LD approaches. And so what's left again is, you know, four or 500,000 snips that are from the very rare end of the minor allele frequency spectrum with something like tuna biased or inaccurate estimators of your reference frequencies affect only the power, not the type one error. So you're not really biasing yourself in that way. And that could be particularly appropriate for samples that are really outside the HapMap reference group. So we study Mexican Americans and consider that to be an advantage. Here's some examples. So here we're looking at with the, this is the 317k platform in a set of Europeans. And so the direct are the actual 317,000 snips that are examined. The indirect is we drop one snip out and interrogate it exactly as we would with tuna any, you know, as if it were an untyped snip. So it's indirectly assessed through this tuna approach. And you can see there's a very good correlation between the allele frequencies that are indirectly estimated using tuna versus directly assessed by genotyping. And a relatively tight distribution of this, what might be called an error in the measurement estimate. If we go out to Mexican Americans where we only had 100k scan, there's only 100,000 snips available to do the interrogations. We don't see as tight a correlation, but there's a very clear correlation. So we see a little bit more error in measurement. But it's still, you know, a lot better than a sharp stick in the eye for getting you additional information from the rest of the genome. Two minutes, Nancy. Okay. So we get pretty tight. So the higher you set your thresholds for the multi-locust measure of LD, the better you do. So here's something where we're allowing anything to come in as long as we had a multi-locust R-squared values, something between 0.7 and 0.9. If we require it to be above 0.9, you know, you do better. And if you look at the test statistics, so this is a chi-square value. Again, this is with all versus requiring the multi-locust R-squared measure to have been above 0.9. So again, getting pretty good correspondence. Additional information for prioritizing SNPs. So remember that a lot of the first genome scans genome-wide association studies are drawing their cases from samples that were included in linkage analyses or have phenotypes that were previously used in linkage mapping studies. You might choose to prioritize based on existing linkage signals. Of course, there are a lot of genome-wide association studies on the same or related phenotypes being done contemporaneously. And it's hugely valuable to try to put that information together and have almost, you know, your in-silico, initial in-silico replications at the time of publication as they did with the diabetes studies that were published in science recently. But we all recognize we're doing this in part because we want to get at all the genes, so get some sort of a pathway. This is from the genes first identified for monogenic forms of type 2 diabetes and basically knowing what, that one of these was a transcription factor, got us into an entire pathway that enabled the discovery of many others simply through candidate gene studies. That's the position we want to be in and one of the speakers alluded to that before. There are lots of databases available to do that. The problem is those downstream annotations require input of genes and we get our signals from SNPs. So we need better annotation. We have physical annotations that we can use. People talked about LD relationships to local genes, expression phenotype information, and we also need to know how well each gene is interrogated either directly or indirectly by our platform as we go into these studies because if we don't, we'll make mistakes. So you can put in a set of genes into one of these pathway programs, look for functional annotations that are over or underrepresented, and one of the things that might come out, for example, is the genes involved in immunity and defense being underrepresented and that's just because the platform did a poor job of interrogating those genes, so we need to take that into account as weights and this sort of annotation can really change how you think about the meaning of a SNP. So here we've got a SNP in the middle of an intron within a single gene and so physical annotation classifies that as an intronic SNP in a certain gene. But if we look at how well the variation at nearby genes allows interrogation of that SNP, how strong the LD between that SNP and the other genes is, we see that it's just as it's in very strong LD with not only the gene that it's in, but in an adjacent gene as well. That's really useful information for taking forward it as well. And if we considered the information on expression just in lymphoblastoid cell lines of that SNP with nearby genes, we learn globally this SNP predicts expression of genes on a couple of different chromosomes, but it also predicts quite strongly, P10 to the minus 6, the expression of this adjacent gene. So not only is it in LD with this gene, but it predicts its expression reasonably well. And if we look at sort of the local rank, it's only 5 out of 22 of the SNPs in this gene for predicting that gene's expression, but it's the top one here in this gene with the P value of 10 to the minus 6 and not really doing much of anything here. So that changes a lot how we think of what genes might feed into the downstream bioinformatics approaches. And this is a database that we're working on and hope eventually to turn over to people who really do databases like DB Gap. So my colleagues and collaborators and Terry talked about the waves of data and we're just hoping to keep everybody from turning out like this porous surfer dude when they do their genome-wide association studies.


have you ever watched a magician work a really good sleight of hand artist can pull lighted cigarettes from the air he's able to saw a woman in half he can pull a rabbit out of a hat or make a fountain pen disappear but have you ever seen a magician who could make a 200 pound corpse disappear allow creeps this is t4 why opening the doors of the mystery play house our story tonight is an imaginative tale called who took the corpse it was written by dl champion the little town of pernville's only scarlet crime was born of a corncob pipe and grew to the stature of the celebrated case when its corpse vanished the crime involved three men one became the corpse another the killer and the third lived to record tonight's story it all started one night in the palace bar where sit dotan the police deputy watched pernville's newest resident amuse the mill hands with clever card tricks the newcomer was good he was a magician a suave satanic figure in a red lined cape he called himself marvelo and marvelo sit dotan noticed as he crowded into watch carried his many drinks well and now gentlemen a flip so a shuffle so and here is your carefully concealed card the ace of spades now gentlemen well the man who was smoking that horrible pipe desist the odor is offensive i guess he means that corncob of yours said may i see that pipe sir oh sure let me knock the ashes out first hey i uh i placed the horrible object on the bar so then i placed the magic cloth over it so what you're gonna do marvelo make it smell like violent no no i will do better than that my friend now a magic word do shavi presto and you pipe well hey somebody should have made disappear a long time sir don't you approve a new pipe for an old one nope i like my old one let's have it i'm terribly sorry sir i can't bring your old pipe back it's an a limbo beyond my call bartender another scotch please marvelo there give me that pipe you sir an individual i dislike a poor sport might be but i'm a deputy and also i think you've had a lot of drinks and also i think i ought to take you home now come on it'll be most unwise of you to lay a hand on me my friend yeah i know i know now come on i told you not to let me what you're doing sitting on the floor lots of chairs around hey that's what they call jiu jitsu isn't it now bartender that's scotch please hello said hey ain't your breakfast off the mantle this morning sure it did well i guess you heard what happened last night chief hey what the devil you're doing rolling your own cigarettes now yeah yeah ain't breaking in new pipes and marvelo never gave me back my old one i'm going to the bank now lamb that's right it is payroll day at the mill unit oh hang it said you used to knock pipe ashes out all over now you're spilling cigarette tobacco on me i'm sorry lamb i'll see you later and i'll be at the palace tonight in case the boys rough it up yeah best deputy in the state but the untidiest man i ever seen you can tell it's payday huh said yep palace is you're busy tonight turn uh uh what here comes your pal marvelo gentlemen gentlemen may i have your attention gentlemen please thank you who's going for you said shut up tom and listen card tricks and feet of magic are merely a profession gentlemen my basic interest is the study of the occult the black art very few men gentlemen have gone as deeply into the forbidden realm of evil as i very few men possess my power what's he driving i read men's hidden thoughts i see their souls mirrored in their minds tonight in this room a man plans murder that man plans to murder me you're all my witnesses i will point this man out to you by means of this because night all right marvelo you asked for it this time i don't know magic but this is a 38 and these are handcuffs and tonight you can study your black books in our jail no jail and no steel handcuffs can hold marvelo you idiot what do you say we just try it huh see in court marvelo a little quiet please next case daniel big xelius marvelo where's the defendant said doton's upstairs getting him out of his cell your honor well what's keeping him somebody go up and deputy where's the defendant he's gone judge gone what do you mean gone where wasn't he in the cell oh he was locked in the cell with handcuffs on and i locked the outer door too but he's gone well that's ridiculous any signs of escape no the door is locked from the inside and the bars are solid he's he's just disappeared in the thin air but i'll find that black devil your honor with the last thing i do i'll find it could very well be the last thing you do mr doton all right how did you get out mr big your honor how could you expect me to tell you that the black arts reveal their secrets only to those who keep them yes well here's the secret the court will share with you in fernville we don't go in for throwing knives around in public places what is all this grudge between you two doton your honor this guy has a screw loose somewhere he goes around thinking that i want to kill it and so you do a half hour after i left the palace the first night i met you your animal brain had conceived a carly plot to murder me and to hide behind your badge of office that's a lot i warned you last night publicly today doton before this court i warn you that your plan won't work because i am going to kill you first are you told it to him did you hear that yep now look marvellous for that kind of talk i can arrest you again for killing i can hang you you got that straight hang marvellous my friend if your deputy doesn't change his mind about murdering me i will kill him and you will be powerless to stop me or to hang me or even to prove i have committed a crime don't trust him sit keep an eye on him yeah yeah he's just a nut oh that doesn't bother me lamb but i'll watch him hello this is freight office hello tom this is said doton say did they expressed up today yeah that's right new radio with a phonograph gadget sure i got it from a wife's birthday now look i took a room at the palace hotel room 212 i want to keep it there and try it out uh send it over tomorrow will you now don't forget room 212 hey bartender oh hey i must see your first customer yeah you sure marvell think new and yet will it be double brandy please right there you don't come around till night usually come here so early yes it is unusual isn't it but then it isn't every day that that one kills a man i'm going to room 212 hey that's doton's room he's up there now there's new radio yes i know how do you know it's a secret how i know is my secret hey you can't uh he's nuts he wouldn't do that and tell me about it sit can handle him anyhow in which direction is room 212 please 212 it's right here sir that door over there thank you thank marvell you can't say i didn't warn you don't know you idiot don't put away that gun now you're hang now don't marvell don't look what do you want this is it doton and after you're dead they won't be able to bury you because they'll never find your car i saw him i saw him do it i saw him lying right there in the blood yes i saw him yeah sure he's dead marvell no he's just standing in front of the room grinning yeah yeah bill sanders has got him covered with my shotgun yeah yeah we'll hold him hurry up will you all right here comes the sheriff now yeah there he's coming right upstairs hi bill take the shotgun out of his ribs well marvell you weren't bluffing to tell me you're actually killed shit you're the police chief mr tracy you expect me to testify against myself is the gun thanks open the room door bill what's going on here somebody being funny there ain't no one in this room i saw him i saw him lying right there mr tracy there's blood all right the closet's empty windows locked on the inside this is radio half out of the crate well marvell where is it where is what mr tracy doton's body it's me i see bill how long did it take you to get up here after the shots well long enough to grab the shotgun under the counter and run up the stairs about three or four minutes where was this guy when you got here bill right where he is now chief look you that's how to be in my deputy and a fellow human said doton was a good friend of mine and i can promise you you'll dance on the end of a rope for this come on you're under arrest what for may i ask murder murder but you have no corpse no corpus delicti how can you arrest me for murder i can hold you for 48 hours on suspicion of murder i should be able to find sid's body by then lm and i'm the middle just call to see if sid was here they're waiting for him to bring the payroll down oh well now isn't that a coincidence marvellou you sure picked a fine day for it didn't you now i've got to find a 110 000 payroll as well as a corpus delicti well then maybe the guy really used magic to get rid of doton as a district attorney you make a lousy detective melton you realize i had to turn that killer loose in 12 hours how about the bullets did you find them marvellous gun shows he fired four chambers it's a 25 that caliber slug stays in a man's body you search the palace top to bottom he didn't hide it there how about his house even superman couldn't carry a corpse over the other end of town and come back in four minutes but i search anyhow the only thing missing was his car he's got a bill of sales shown he sold it to a dealer who drove it west three days ago okay marvellou in the first round i can't hold any longer yes well thank you for your hospitality chief uh tracy i think i will leave fernville that is if i may sure sure you're free until i find sid's body that is no i'm by the way you better spend that payroll money it took from sid fast well you're going to wind up it ain't going to be much good to you hello melton yeah lamb what's up i think i can crack this case i just got a report on marvellous car i can't make an arrest of course but the chicago police have been able to tail the car and they've told me where marvellous living there he's apparently been there since he left here four days ago i'm leaving for chicago today taxi taxi look son i want you to drive me out toward jarrington park there's no farmhouse out there i want to get to i'll tell you where to drop me off okay pop all right son let me off at that crossroad don't you want to go to the house you want nope i'm on a surprise a friend of mine hey i said keep a chain thanks mister mail box daniel bigs and there's marvellous car in a driveway that does it good evening chief trafie marvellous put up your hand well marvellous thought you'd be in the house i'm getting careless i guess yes very careless my friend i was afraid you might track down my car but it doesn't really matter just keep your hands on side please let's go inside where it's more comfortable shall we believe me i regret having to do this mr uh tracy hey you'll probably regret it longer than i will i'll do you one favor tracy as a detective there are aspects of this case which you might like to know about i'll answer any one question for you just one question tracy before you die hmm it's very thoughtful of your marvellous i'm told all right what did you do with sid's body your deputy it's sid sid don't first time i ever had a corpse saved my life sid sure glad to see you tell me what happened sid sure uh give me a match for it's a yeah thanks well there's lots of it that i i don't know lamb marvellous comes in the hotel and fires at me there's a puff of black smoke from the gun and i pass out what then well i don't know where he hid me but i woke up seemed like years later in the trunk compartment of this car ain't not if marvellous dead will never know how he worked it how'd you get away from it work the ropes loose this afternoon hitting the orchard i knew he'd taken a payroll from us i saw him nab you so i waited then i moved in hang it shit why do you knock your pipe ashes out on floors i'm sorry lamb i forgot hey why you stopping here lamb well might as well get some gas besides i got a phone chicago police about marvellous yeah you got a phone here right inside the door thank you hello police headquarters give me deputy green please hello green this is tracy from fernbill yeah so you send that squad car down the turnpike to let this gas station with you yeah i got them both the corpse and the killer sit you were listening yeah i was listening i'd come in behind you crazy don't try anything sid try anything oh i i'm blessed you but i'm sorry you made me do that said i'm arresting you for the murder of your partner daniel biggs alias marvellous that bandage will hold you till the squad car gets here said light your pipe if you want it oh thanks how'd you figure it out lamb oh well i don't believe in magic said marvellous had to have an accomplice to get out of jail you're the only one who could have helped in stage that hokum that it all you had to go on no no man has habits said little habits like pipe smoking oh you said you never got your old pipe back from marvellous and then you pulled it out when we were in the car yeah i i got a guess how do you how do you dope out my disappearance well marvellous probably shot four blanks at you you cut your arm for the blood the gal saw you lying there and she ran out you went out the window to the roof and marvellous locked the window after you and i figured you made it to the car outside of town and waited for marvellous to show up and of course you had that payroll with you so i found a good little marvellous car and by shooting marvellous you probably thought he was going to spill the setup to me you're right you know i wouldn't have had to split the payroll with him i should have stuck to my old profession huh lamb hey um you should have son or you should have stuck to cigarettes oh hang it said why didn't you learn not to empty your pipe ashes all over you're the untidiest guy i ever seen i'm sorry lamb i forgot sorry yeah i'm sorry too said mighty sorry come on let's go son any others the first case in history where the corpse becomes the killer and the killer winds up as the corpse the story was called who took the corpse this is t4y closing the doors of the mystery playhouse and saying good night sleep tight this is the armed forces radio service


All right. Sa internet, um, I will not be able to do. Pwede magtanong tonight. I'll be out. So, but I did want to get some of the, oh jeez man, and it even, di ko pa nalang naklik yung search for server button. So, I won't be in later. So, wala mo pwede magtanong. We'll have to do it next Friday. But I didn't want to get working on some of the deliverables for the sponsor. So, we'll be doing a quick game stream, and you notice that, you notice that, you notice that, you notice that I've gone back to our old lens, gone back to the old lens, because the other one was just two. The other one was just two in focus. Di ko mo nang sya tinaman ng pistol. Grabe naman. Oh, sub mark louis, sub mark lester. Oop, I have the bomb. So, can't even, trying to read the chat, and it's, trying to read the chat. So, nalito ako. Cut one. Okay, quick peek. Oh. Quick peek, but not quick enough. Oh, sub-tech wolf cave. Bandamin yung online at this time. Wala mo may trabaho? What time is it? Like, four in the afternoon. Three in the afternoon. Oh, nice, nice. Naikutan. Good job. Oop, naikutan din. Ha! The one who went around, naikutan din. Oh, not bad. All right. I played yesterday. Oh, such a bad game. Such a bad game. Yes, I'm just trying to get back into the groove. I didn't get to play much over the holidays. I did unbox, or I did unlock a crate yesterday, but I didn't get anything good. I don't usually play Valor just because I don't know the... Diyaw sa nice characters. Like, I don't know their abilities. Man, I only lost four people there. At least that guys are more competent than me. Kungaman lang ma... Ah, maytaba, maytaba. Always with the waiting. Modern CS, always about the waiting. May magabang, may magabang. Oh, two health! Kainis! Somebody please kill that, guys. So, I'm going to assist. Did I hit him, ba? I haven't tried the new stuff in Cyberpunk. That's another game I want to get back to. Actually, the weekend was really like, I didn't have any... the weekend, the long holidays. I didn't get much gaming done. I have three deaths already. It's been three rounds. Oh, I got my assist. Ha! Pitik na lang yun. Not a time. Oh, there's my gun. Ha! Even got my gun. Magandabay ang baril na to. Cham. Kandang na mga... Oi. Ha, ha, ha, ha, ha. So, it'll be a little bit faster with the flashbang. Ha. Oh, somebody is still using my gun. Glad to see...  Faster. Tamaba? Parang. That's my gun.