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rc3 preroll music
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Herald: Welcome back in Halle with Chaos[br]Zone TV, the next talk, will have
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interactive elements, so here are the[br]hashtags again. We're on Mastodon with
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@Twitter with the hashtag RC3 Chaos[br]Zone and on the IRC channel in Heckint and
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which is RC3 Dash Chaos Zone. All right. Lisette[br]will now speak to us with a talk called
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"What the Health Beyond Genome[br]Sequencing". Since the 80s, the Human
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Genome Project set goals to technical and[br]ethical goals to understand the human
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genome. In recent years, these goals have[br]been achieved, and humanity could profit
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immensely from what the sciences and the[br]technology the methods could be developed
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through the project. Lisette works at the[br]bleeding edge of what it is now a hard
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data science. We are very excited to hear[br]about the considerations and the
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practicalities of advancing the biology[br]even further.
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Lisette: OK. Yeah, thank you very much for[br]the introduction. It's my pleasure to give
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some insights into what I've learned[br]throughout my studies and what I'm now
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actually also working on. So thank you for[br]providing me this slot. I was a little bit
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surprised when I thought, Oh, OK, now I[br]actually have to give the talk. So please
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forgive me if I'm sort of nervous, but[br]stay with me and thank you everyone for
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watching and for filling in the survey[br]beforehand, and you will have another
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option to participate in the poll later[br]on. So I have some things to announce
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first, which would be about the content.[br]So it will all be very abstract. So we are
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talking more about concepts than[br]about actual disease and suffering. So
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there will be no photos. But yeah, the[br]general theme is about medical
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examination, everything clinical, about[br]the patient assessing somebody's disease
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and disease risk, and also going into the[br]more severe conditions of which you might
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die. And we also touch upon family[br]relationships. So just so you know, yeah,
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it will come back every now and then. So[br]just for everyone to be aware. And then
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also, yeah, I need to disclose that I'm an[br]employee of a company that does work on
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marketing genetic tests. So that set[br]aside, this is not this is not any kind of
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advertising talk. It's really about what[br]is actually happening technology wise. So
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I want to give you the insights into a[br]little bit of the technology, how it came
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about and where we are now, and also try[br]and give you an overview of what are the
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options in terms of genetic testing for[br]various utilitys and raise awareness just
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for also the ethnical issues that might[br]arise from what we can learn from our DNA.
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So this is enough of the prolog. Let's go[br]right into looking at a patient which is
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classically done from the outside. So we[br]want to know what is different about this
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person or a patient. And yeah, there are[br]really layers of information, and you
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always assume that there's a relationship[br]with a condition. So be it a rash that you
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see on the outside or as swelling that the[br]doctor can't feel or something that they
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learn from interrogating the patient. And[br]then there's a bit of a borderline outside
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inside test, which would be bodily fluids.[br]So if you test urine, saliva, blood, yeah,
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you already look on the inside. So what's[br]happening inside of the patient and the
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metabolome? Yeah, what's what's going on[br]in terms of small molecules that you might
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detect with the one or the other test? And[br]also what you can see on the inside is
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broken bones or cysts that shouldn't be[br]there. So for that, we use imaging which
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where x-ray is the oldest, and then[br]there's magnetic resonance and pet
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scanning. So these are like the cool,[br]advanced additional layers where you can
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look inside of the of the patient. And[br]then of course, there's DNA. So if we look
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even deeper and inside each cell, you will[br]have the genetic code of this person, so
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to tell how they are different on a very[br]small scale. So that is the dogma of
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molecular biology that you go from DNA,[br]which is your genetic blueprint, and then
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certain parts are transcribed so the cell[br]makes copies of the DNA, which what I'm
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called RNA, because it's a different[br]chemistry and these are then translated
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into chains of amino acids, so there's a[br]code which amino acid should be attached
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to which one. And then you fold it[br]properly and then you have a functional
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protein. And then now why you sequence the[br]DNA is because you assume that there's a
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mistake made, which then leads to a faulty[br]protein. And then in the end, something in
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your body doesn't work. So, yeah, it's a[br]very simple concept, if you will. And
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then, yeah, when we check in the DNA and[br]in the RNA is about 20000 protein coding
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genes. And then there's also a different[br]types of RNA that do not code for proteins
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that regulate other stuff so that the[br]correct genes are actually transcribed and
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translated. So that's an additional 20 to[br]30 thousand, potentially more. And so if
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you combine any of these two, see like a[br]certain signature of a person, you already
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have billions of combinations. So as you[br]can imagine, there are many, many, many
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signatures possible. But yeah, which of[br]these will actually tell you something
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about the patient? So. Let's go back to[br]how we sequence the DNA. So it is actually
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very simple. All of our usually 46[br]chromosomes so that 23 pairs are made of
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at double stranded code, which is the DNA.[br]And then you see here in the unfolded
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region that where a gene is starting, it[br]usually starts with A T G and these are
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ciramated bases. So you have here in the[br]chemical metal insert and the A and the T,
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which form a pair. So the red thing is in[br]between are hydrogen bonds that keep them
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together. And A and T always want to be[br]together. And C and G always want to be
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together. C and G actually form three of[br]those bonds. So in a little bit more
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stable. And so as you can see, this double[br]stranded DNA is hands always inverted on
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the other strand, so we call it the[br]complementary strands. So if you have ATG
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on one strand, you always have TAC on the[br]other. So you only sequence one and we
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defines the direction of the gene because[br]we know in which direction it makes sense
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because, you know, only in one direction[br]you can then make a protein out of this
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code. So enough for the chemistry and the[br]principle. So we really want to know and
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to map where on each chromosome, which[br]letter occurs. So you can imagine that
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this is quite an adventure and takes a lot[br]of effort. And actually, it has also
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started very early on in the 70s. So maybe[br]you have heard of Sanger sequencing. So
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that was the first generation of[br]sequencing from 1977, where you
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essentially cut the strand in little[br]pieces and you know which one ends with an
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A, ends with a T.. So you have all kinds of[br]fragments with different lengths which run
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over a gel, which is not that important.[br]But it's it is also called capillary
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sequencing, which then helped finding the[br]first human disease gene, which is called
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the Huntington team. You might heard of the[br]disease where it belongs to Korea,
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Huntington's. And so this was the first[br]association that was really confirmed
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that, OK, you have a defect in a certain[br]gene, which directly translates into a
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disease phenotype, but this is very rare.[br]So usually it is a lot more complex and we
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will also get to that. So the capillary[br]sequencing still lasted for a while, so 10
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years later, you had really cool[br]instruments for the first time from
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Applied Biosystems so that you can[br]sequence a little bit quicker, but still
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far from looking at the whole genome. So[br]that was then planned starting in 1988.
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They defined the goals for the Human[br]Genome Project, which would then take from
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1990 until 2003 to complete one full human[br]genome. So full in the sense that it still
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had gaps. So there are some regions which[br]are tricky to sequence, so these gaps were
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filled later on. But still, yeah, this was[br]a huge undertaking which cost about two to
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three billion US dollars. And eventually,[br]in 2000, they announced that they had a
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first draft of the human genome, and then[br]it got published in 2001 in the two big
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scientific journals, Nature and Science,[br]both on the cover the human genome. So
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that was and is a big step. So it's yeah,[br]that's just crucial to know, what we are
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looking at to have a map of our complete[br]genome, where then you can map other
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people's sequences to as well. So that's[br]what started also in 2005. But then for
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different types of cancer, it's called[br]TCGA from the genome, the Cancer Genome
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Atlas, and it also lasted for a couple of[br]years. But then they were much quicker in
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sequencing, because 2005 was also the year[br]of next generation sequencing machines. So
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nowadays we don't do Sanger sequencing[br]anymore or rarely. We usually rely on
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heavy, high throughput parallel sequencing[br]so that you can sequence a lot more
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different pieces, so to say, at the same[br]time and with very high accuracy. So
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essentially, this means, that we now have[br]access to 3.1 billion base pairs, which
0:14:26.160,0:14:33.360
were first collected during this human[br]genome project. And this nice
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advertisement when they were looking for[br]volunteers is really cute, actually,
0:14:38.640,0:14:46.240
because they also say here that this photo[br]of the project will have tremendous impact
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on future progress of medical science and[br]lead to improved diagnosis and treatment
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of hereditary diseases. Volunteers will[br]receive information about the project and
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sign a consent form. No personal[br]information will be maintained or
0:15:04.080,0:15:12.800
transferred, and a small monetary[br]embarrassment will be provided. So, yeah,
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they were promised that their data would[br]be kept anonymously and also they
0:15:21.920,0:15:29.440
collected blood from female volunteers or[br]sperm from male volunteers. And then they
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collected a lot more samples than what[br]they would need so that in the end, you
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couldn't tell anymore from whom the genome[br]was actually derived. And there was one
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volunteer at Roswell Park and hence called[br]RP11, who had happened to have
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exceptional quality sequencing reads. And[br]then so the first human genome was mainly
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based on this one person, and we have[br]multiple new versions published of the
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human reference genome today. Its version[br]38 and still about 70 percent are
0:16:13.120,0:16:23.760
untouched from this first genome assembly.[br]And a small thing about the cost. So I
0:16:23.760,0:16:32.320
mentioned that this was a really costly[br]project. Two to three billion dollars. And
0:16:32.320,0:16:42.320
now we have actually cracked the $1000[br]threshold. So it is possible to sequence a
0:16:42.320,0:16:48.320
full human genome for about a thousand[br]bucks, which is remarkable. So this is
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really an enormous drop in the cost just[br]because the technology made such a big
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leap when we came to the next generation[br]sequencing. And also one genome. If you
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have it sufficiently covered so that you[br]are sure about which base pairs and which
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position, then you have about 180[br]gigabytes of raw rids. And if you align
0:17:21.760,0:17:29.040
them to the reference genome, which is, of[br]course, now your atlas, if you will, so
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you can put all our rids to the correct[br]place. And then this is called an
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alignment file, which is about 80[br]gigabytes. And if you then only keep the
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positions where something is different[br]from the reference genome and you compress
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it, you are left with about 5 percent[br]of that. So 4 gigabytes per person.
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Storable, nice little genome. OK. So this[br]takes me to the first poll, which is on
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simple vote. A couple of people[br]already have participated in the monkey
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survey. Then, yeah, you don't have to do[br]it again now, but the vote link will also
0:18:21.920,0:18:30.240
be in. And you also just fill in any name[br]combination of letters, click OK, and then
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you can answer the first question, which I[br]present here. So this is just three
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statements about sequencing a full human[br]genome. Whether you believe that it has
0:18:43.600,0:18:50.080
replaced fingerprinting in forensic[br]investigations, where do you think that it
0:18:50.080,0:18:56.400
gives you all the clinically relevant[br]information for any patient and whether
0:18:56.400,0:19:05.280
you think that it is cheaper than a full[br]body MRI scan? So yeah, we will get to the
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results in a bit. I will just continue[br]with a couple more slides and then we can
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see. What do you guys think, and I'm[br]really curious to actually hear that. And
0:19:19.840,0:19:31.360
see it for myself. Let's see. So if you[br]think in terms of complexity, we have
0:19:31.360,0:19:38.320
already touched upon Korea, Huntington,[br]which is a single gene, essentially that
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gives you a full blown disease if it's not[br]encoded properly. And then you could think
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of other diseases that are encoded by a[br]couple of genes, where you can think of
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breast cancer over a couple of mutated[br]genes can give you a much higher risk than
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average population. And also in[br]Alzheimer's disease, we see that
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hereditary component. Brought about by a[br]couple of genes again and then more
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general in terms of unknown diseases, you[br]can ask gene panels or full genome
0:20:31.520,0:20:38.000
sequencing to help out. And it gets more[br]and more fuzzy, but more and more also,
0:20:38.000,0:20:44.960
tests are available if you want to go to a[br]prognosis for this or that condition or to
0:20:44.960,0:20:51.680
the correct treatment choice. So I'll try[br]and give you a couple of more examples,
0:20:52.800,0:21:02.240
but only after we have talked about the[br]Cancer Genome Atlas, the PCGA . So here
0:21:02.880,0:21:10.960
that's also a lot of data. So they claim[br]2.5 petabytes were collected in the place
0:21:10.960,0:21:22.320
it was running from 2006 to 2014. And[br]yeah, in total, 33 different tumor types.
0:21:22.320,0:21:28.960
And they did not only look at the DNA and[br]all the mutations, but also RNA and also
0:21:28.960,0:21:39.840
proteins, and also different info on the[br]patient's survival and treatment data. So
0:21:40.560,0:21:48.000
that is a huge pool and resource of data[br]where people are looking at and finding
0:21:48.640,0:21:55.600
signatures of patients with less or more[br]advanced cancers with patients that
0:21:55.600,0:22:01.360
progress through treatment or not. But[br]it's all. Yeah, you still really need to
0:22:01.360,0:22:08.640
take it with a pinch of salt because, for[br]example, since 2006, treatment of cancer
0:22:08.640,0:22:14.640
has changed tremendously, and you cannot[br]just use any signature that you took from
0:22:15.520,0:22:22.640
the data from PCGA and extrapolate for[br]today's cancer patients. So that's a bit
0:22:22.640,0:22:30.720
tricky. PCGA still vastly used. But then,[br]yeah, I would propose that you should
0:22:30.720,0:22:39.120
rather use it for validation so you find[br]something in current data from today's
0:22:39.120,0:22:45.120
patients and then you can check whether[br]this was also seen in the PCGA data and not
0:22:45.120,0:22:57.114
the other way around. But let's get to the[br]results of the poll. See? Can we go there?
0:22:57.114,0:23:21.277
What happens? Oh, nice. What's the score?[br]7.3 So you mostly agree that full body MRI
0:23:21.277,0:23:30.210
is more expensive than the full genome[br]sequencing, which is true. So like I said,
0:23:30.210,0:23:38.880
the whole genome is now about 1000 dollars,[br]also 1000 euros, and the full body scan in
0:23:38.880,0:23:49.600
the MRI will cost about two to six[br]thousand euros, roughly. And then this one
0:23:49.600,0:23:58.320
with the fingerprints I have made up. So[br]sorry to fool you. This is not done yet.
0:24:00.000,0:24:07.760
And it also cannot potentially give you[br]all clinically relevant information about
0:24:07.760,0:24:17.840
the patient. So nice. Thank you for[br]participating. And also, I check the
0:24:18.640,0:24:23.680
survey monkey and also there. I have[br]managed to fool some people into believing
0:24:23.680,0:24:32.640
that. It's possible to replace[br]fingerprinting with full genome
0:24:32.640,0:24:41.440
sequencing, where that's not true. Sorry.[br]So let's go to another level. So not only
0:24:41.440,0:24:46.960
the DNA sequencing is interesting. So then[br]you have the map and on the property,
0:24:47.520,0:24:56.080
sorry, on the DNA strand, you know, for[br]example, where there's a different letter,
0:24:56.080,0:25:04.640
if you will. And then in the reference[br]genome, and then this mutation might be in
0:25:04.640,0:25:11.840
one of the regions where the DNA has[br]stored the code for a certain protein like
0:25:11.840,0:25:17.600
protein one or protein two. So the code[br]might be different, but also it might be
0:25:17.600,0:25:26.640
different how many copies are made. So[br]this is an example here where gene one and
0:25:26.640,0:25:33.760
two are equally often transcribed. And[br]then there's these transcripts, which we
0:25:33.760,0:25:41.840
call messenger RNA about equal amounts.[br]And this is, let's say, the state how it
0:25:41.840,0:25:50.080
should be in the healthy adult. And if you[br]think about any condition like a cancer
0:25:50.080,0:25:57.600
tumor, then it might get deregulated and[br]the cancer, for example, then there's this
0:25:58.240,0:26:03.440
and only makes very few copies of gene[br]one. And a lot of copies of gene two,
0:26:04.160,0:26:12.480
which might lead to effects like bigger[br]growth, faster faster growth, bigger
0:26:12.480,0:26:21.280
spread into the tissue, which would[br]normally confine the tumor. So that is
0:26:21.280,0:26:27.360
also one level of regulation and that you[br]cannot usually capture with DNA sequencing
0:26:27.360,0:26:32.880
or whole genome sequencing. For that, you[br]need to check for the expression which you
0:26:32.880,0:26:40.080
do on this level, on the RNA level. And[br]then you have they call in differential
0:26:40.080,0:26:47.600
expression, which gives you this kind of[br]picture analysis. So you have some
0:26:47.600,0:26:54.560
samples, vertical and then horizontal are[br]the genes, and you see that if you compare
0:26:54.560,0:27:01.040
the samples, some genes are more[br]expressed, which is red and some genes are
0:27:01.040,0:27:08.240
down compared to the others, which is[br]green. And then you can find clusters of
0:27:08.240,0:27:15.840
genes, a group of genes here in the red[br]bar, where Group one, in that case, a
0:27:15.840,0:27:23.040
certain kind of breast cancer is highly[br]upregulated and most of the people I
0:27:23.040,0:27:27.680
belong to, group two different kind of[br]breast cancer have lower expression of
0:27:27.680,0:27:35.600
that team and and the blue cluster is the[br]other way around. So that gives you an
0:27:35.600,0:27:42.080
idea of OK, you can maybe use one of these[br]genes to differentiate between the two
0:27:42.080,0:27:47.680
groups. And if that helps you to determine[br]what treatment they should get, that's of
0:27:47.680,0:27:55.200
course, super useful. And then you have[br]something like a genetic biomarker. If you
0:27:55.200,0:28:02.640
have multiple genes, then you usually call[br]it a signature. And so these genetic
0:28:02.640,0:28:13.120
signature tests can tell you, are you at[br]risk of a certain disease? They can help
0:28:13.120,0:28:22.560
diagnose or get to the exact subtype of of[br]your disease. They can help you with the
0:28:22.560,0:28:28.880
correct treatment or monitor whether the[br]disease actually responds to the
0:28:28.880,0:28:36.000
treatment, whether anything changes back[br]to normal. And also, it can sometimes be
0:28:36.000,0:28:44.000
useful to give a prognosis for a disease[br]progression. So in the end, you always
0:28:44.000,0:28:50.080
need to wonder what is the added value of[br]such kind of testing on top of the
0:28:50.080,0:28:55.040
clinical variables that are already[br]existing and does give you something
0:28:55.040,0:29:02.320
actionable? What can you do something with[br]the knowledge that you gained from this
0:29:02.320,0:29:08.400
testing? So there we are already at the[br]problems with genetic testing. So that
0:29:08.400,0:29:14.880
would be the second question that you can[br]answer again on Simple Vote. Please feel
0:29:14.880,0:29:24.320
invited to help me understand what you[br]think. And here it's just. For you
0:29:24.320,0:29:30.240
personally, the question whether you would[br]want to know whether you are at risk of a
0:29:30.240,0:29:35.760
genetic disease and would you want to know[br]if you had to pay for it and then slide it
0:29:35.760,0:29:39.680
to the right, if you're willing to pay or[br]slide it to the left, if you're totally
0:29:39.680,0:29:45.200
not willing to. And then the second slide[br]is the same question when you want to know
0:29:45.200,0:29:52.400
if you got the results for free? And then[br]to the right is yes, and more to the left
0:29:52.400,0:30:00.160
is no, absolutely not. So again, I will[br]just move on and you can take your time
0:30:00.160,0:30:08.880
answering that one. So to give you a bit[br]of a feeling for what is at stake is the
0:30:08.880,0:30:18.720
get WHO into testing for genetic risks.[br]It's, of course, good to know your family
0:30:18.720,0:30:24.720
history of disease. And also, if you're[br]planning to have children, for example,
0:30:24.720,0:30:30.160
would you want them to know that they[br]potentially carry a certain risk or not?
0:30:32.400,0:30:39.760
Then health or life insurance might have[br]an interest in knowing what people's risks
0:30:39.760,0:30:46.320
are, what they have to expect. So there[br]are certain instances where they are
0:30:46.320,0:30:52.400
eligible to know and certain instances[br]where at this moment in time, they
0:30:52.400,0:30:58.800
absolutely are not. So this is something[br]that's probably going to change in the
0:30:58.800,0:31:05.120
future. The more we know, the more we want[br]to use that knowledge. And then there's
0:31:05.680,0:31:11.520
the problem that some genes are very often[br]found to be up and downregulated, and
0:31:11.520,0:31:17.840
there seems to be a difference. But it's[br]just yeah, in the nature of those genes,
0:31:18.960,0:31:25.200
and we have sometimes multiple signatures[br]for the same problem. And then, yeah,
0:31:25.200,0:31:32.160
doctors and patients just don't know what[br]to choose from. So I'll go through some of
0:31:32.160,0:31:44.640
those issues in more detail. I have[br]mentioned the TCGA before, and this cancer
0:31:44.640,0:31:52.080
genome atlas is really a limited source[br]that is now exhausted, but it's still
0:31:52.080,0:32:06.600
oftentimes used as the silver bullet. So.[br]Let's see if we already have votes. Well.
0:32:10.640,0:32:24.000
So that would be. Yes. OK, so if you if[br]you could know your genetic risk and you
0:32:24.000,0:32:30.160
would get it for free, then most people[br]are inclined to say, yes, I would like
0:32:30.160,0:32:36.960
that very much. And if they had to pay for[br]it, then it seems to go more towards no,
0:32:36.960,0:32:45.120
but it's actually kind of neutral, which[br]was surprising. Yeah, I would have thought
0:32:45.120,0:32:50.080
that you would all say, no, I don't want[br]to know. But that was just my assumption,
0:32:50.080,0:32:59.840
and I was apparently wrong. Cool, thank[br]you. Poll number three third question is
0:32:59.840,0:33:07.760
about a commercially available DNA test,[br]which is not actually sequencing, but they
0:33:07.760,0:33:14.720
use a panel of mutations that are now[br]known because we have already sequenced
0:33:15.520,0:33:22.640
thousands and nearing a million complete[br]full genomes. And yeah, I was wondering
0:33:23.440,0:33:31.440
whether you would know. So that's quite a[br]number three. What institutions they
0:33:31.440,0:33:37.280
partner up with. So this DNA test is goal[br]23 and me. And if you don't know what it
0:33:37.280,0:33:45.520
is, then there's also an answer option for[br]this one. No clue what it is. It does. And
0:33:45.520,0:33:52.480
for the rest, yeah, I propose that they[br]work together with Broad Institute, that
0:33:52.480,0:33:59.280
they work together with GlaxoSmithKline,[br]GSK and they got 300 million US dollars
0:33:59.280,0:34:05.360
from them, that they work together with[br]general practitioners in the US, that they
0:34:05.360,0:34:13.680
got subsidy from Google 4 million US[br]dollars or and Amazon 9 million US
0:34:13.680,0:34:20.880
dollars. So, OK, let's see what you think[br]or how many of you don't know the text.
0:34:23.520,0:34:32.080
And in the meantime, I'll present two[br]cases to you, where genetic testing would
0:34:32.960,0:34:38.800
play a role like, for instance, in the[br]case of inhealthy adult, where the dad was
0:34:38.800,0:34:44.080
diagnosed with this heart condition,[br]hypertrophic cardiomyopathy, where the
0:34:44.080,0:34:50.880
heart tissue gets scars and at some point[br]it cannot pump properly anymore. And so if
0:34:50.880,0:34:56.640
you have one parent with that disease, you[br]have a 50 percent risk that you have
0:34:56.640,0:35:03.600
inherited those genes from your parents.[br]So this healthy adult and their siblings
0:35:03.600,0:35:14.880
got the offer to get tested. So the costs[br]are covered by the health insurance, but
0:35:15.440,0:35:23.520
there is no cure for this condition. So[br]you can. Yeah, have a stricter
0:35:23.520,0:35:29.120
surveillance, and you can get access to[br]early treatment if you develop symptoms,
0:35:29.120,0:35:36.640
but yeah. Other than that, yeah, it's[br]still just a risk gene. So to say so if
0:35:36.640,0:35:41.120
you know you have the gene, it doesn't[br]mean you will get the disease. It just
0:35:41.120,0:35:47.440
means you have an elevated risk. So it's[br]really hard to grasp. And this is one case
0:35:47.440,0:35:54.480
where at least in the Netherlands, the[br]life insurance would be eligible to know
0:35:54.480,0:36:01.920
if you got tested and you do have that[br]gene. So in the end, this person said, No,
0:36:01.920,0:36:08.720
no test, please. I will just go see a[br]cardiologist every now and then, have it
0:36:08.720,0:36:14.480
checked nonetheless. But I don't want to[br]know if I have those things OK. A second
0:36:14.480,0:36:27.040
case? Yeah. So that's an infant delayed in[br]development. It was still a bit fuzzy.
0:36:27.040,0:36:34.560
Like what should an infant be able to do[br]or not do at the age of one? But then the
0:36:34.560,0:36:44.480
parents started observing seizures in the[br]in that case, it was absences, so it was
0:36:44.480,0:36:53.040
not cramping, but just very absent. So[br]eventually, they got access to tests,
0:36:53.040,0:36:59.840
genetic tests where distinct genes were[br]analyzed. Nothing was found. Then panels
0:36:59.840,0:37:05.360
of genes with increasing size and nothing[br]was found. And then the whole genome
0:37:05.360,0:37:13.520
sequencing was done. And then you always[br]have to compare to the parents. And
0:37:13.520,0:37:22.400
essentially, parents and child who trust[br]that and the child had a mutation in a
0:37:22.400,0:37:29.680
gene where the parents had nothing and it[br]was just the very rare X-linked mutation.
0:37:30.320,0:37:39.520
And eventually they now know what is going[br]on, which was only due to the possibility
0:37:39.520,0:37:47.360
of whole genome sequencing. And in the[br]end, the parents also said, Yes, I want to
0:37:47.360,0:37:53.040
know what else is found in this whole[br]genome sequencing. So that isn't actually
0:37:53.600,0:38:03.840
case free, where one of the parents is the[br]carrier of a mutation in a in a protein,
0:38:04.560,0:38:14.240
that when it's faulty or when you get a[br]faulty version from both parents, then you
0:38:14.240,0:38:19.520
will develop this condition. Cystic[br]fibrosis. So that is really good to know
0:38:20.640,0:38:26.800
when you are a carrier of this and also[br]your future kids can get tested to see
0:38:26.800,0:38:35.440
whether they got this faulty version[br]from you. So let's have a look at the poll
0:38:35.440,0:38:48.480
number three. This is here. So the DNA[br]test 23 and me. Let's see where's the. I
0:38:48.480,0:38:55.440
have no clue what this test is. So this is[br]just a four. OK, so not that many people
0:38:57.680,0:39:07.840
voted for this one. Twenty nine votes. Oh,[br]well, actually. Twenty nine votes. And
0:39:07.840,0:39:20.080
then what you thought it would do. So[br]you'll have here, you approve of it,
0:39:20.080,0:39:25.200
working in conjunction with general[br]practitioners in the U.S., which is not
0:39:25.200,0:39:32.400
true. Sorry. Yes, it did get subsidy from[br]Google, 4 million US dollars in the
0:39:32.400,0:39:43.840
very beginning. No, no, no. Sanger[br]sequencing Yes. GSK 300 million. They want
0:39:43.840,0:39:52.800
to use their data to find new drug[br]targets. And I also made this one up. So
0:39:52.800,0:40:00.560
Amazon did not give any money to 23 and[br]me, but you can order through Amazon. So
0:40:00.560,0:40:13.600
that's possible. OK, thank you. And I'll[br]think I will wrap up after just presenting
0:40:15.120,0:40:21.760
this problem here quickly. So breast[br]cancer is one of the pioneering fields of
0:40:21.760,0:40:30.080
genetic testing. So you have five[br]commercially available tests that can tell
0:40:30.080,0:40:35.760
you what type you have, what treatment[br]options would be best for you and what
0:40:35.760,0:40:42.480
your prognosis is. So you really need a[br]well-informed team of doctors if you want
0:40:42.480,0:40:51.040
to make use of this. OK, I'll skip a few[br]slides. Mean, validation is important.
0:40:51.040,0:40:57.040
Takes a lot of time. And I think in the[br]future, it's not only going to be a whole
0:40:57.040,0:41:03.280
genome sequencing, but there will be a lot[br]more to it, like the immune system and
0:41:03.280,0:41:10.114
your gut microbiome and everything, which[br]is in there is also, of course, influenced
0:41:10.114,0:41:16.899
by outside factors what you eat, how much[br]sunlight you get, how much you move. So
0:41:16.899,0:41:23.645
this is also already available, this data[br]from your smart watch, for example. So I
0:41:23.645,0:41:30.040
think in the end, if we get to[br]personalized medicine, this will also play
0:41:30.040,0:41:36.880
a role. And to recap, if you sequenced the[br]whole genome, this is not the same as
0:41:36.880,0:41:43.557
ordering any tests online, where you also[br]might run into data security issues with
0:41:43.557,0:41:52.326
tests like 23 and me. And that's also not[br]the same a deceases signature. And then, yeah,
0:41:52.326,0:41:59.358
if you have a new cool diagnostic[br]signature that is published, it might
0:41:59.358,0:42:05.537
still take a long time and couple of[br]validation studies before it actually
0:42:05.537,0:42:12.876
enters the everyday clinic and you get it[br]reimbursed from your health insurance. And
0:42:12.876,0:42:19.440
for this, it also needs very well trained[br]physicians and informed patient and
0:42:19.440,0:42:27.240
family. I think there's no way in stopping[br]this. But that's just my take. So we will
0:42:27.240,0:42:35.105
see a lot more from the molecular side of[br]things in the future, and these are also
0:42:35.105,0:42:42.414
to be retrieved online. So everything all[br]the tests that are registered also you can
0:42:42.414,0:42:47.762
filter for countries, for Germany, for[br]example. And then you see even which
0:42:47.762,0:42:55.786
university clinic offers which kind of[br]testing. And if you ever hear the term
0:42:55.786,0:43:03.400
liquid biopsy, that's usually a black[br]sample where, yeah, all kinds of things
0:43:03.400,0:43:09.200
are measured, so you have DNA in there,[br]but you also have metabolites in there,
0:43:09.200,0:43:15.640
you can have little fragments of cancer[br]cells and cancer derived DNA. So this is
0:43:15.640,0:43:21.884
something that's coming forward more and[br]more that you just need a blood draw. And
0:43:21.884,0:43:29.367
then, yeah, you have a lot of insight, not[br]only the whole genome, but even more RNA
0:43:29.367,0:43:37.517
sequencing data, for example. So thank you[br]very much for inviting me, for listening,
0:43:37.517,0:43:48.655
and I'm happy to take your questions now.[br]Herald: It's again, the social media
0:43:48.655,0:43:55.040
hashtags on Mastodone and Twitter [br]RC3ChaosZone without a dash and then on
0:43:55.040,0:44:01.030
IRC unchecked, and the channel is RC3[br]with a dash. Chaos Zone.
0:44:01.030,0:44:05.662
Lisette: Do we already have any specific[br]questions?
0:44:05.662,0:44:10.664
Many think people would like to know.[br]Herald: And targeted gene modification
0:44:10.664,0:44:16.933
with CRISPR and Cas9 is not even allowed[br]on plants and animals in the EU. Do you
0:44:16.933,0:44:21.154
think there will ever be gene therapy for[br]humans?
0:44:21.154,0:44:35.360
Lisette: There was gene therapy. So, for[br]example. I'm not sure whether it was a
0:44:35.360,0:44:45.440
typo, low key a or an immune defect where[br]they tried to cure children with gene
0:44:45.440,0:44:50.282
therapy, so there were clinical trials,[br]but something went horribly wrong, and I
0:44:50.282,0:45:01.040
think actually one of the children[br]suffered so much from how they inserted
0:45:01.040,0:45:10.560
the gene that it developed a type of[br]cancer. But I'm still hesitant to say that
0:45:10.560,0:45:18.480
this is the end of gene therapy. So it has[br]potential in very severe cases where
0:45:18.480,0:45:24.960
there's no other option. But yes, it's[br]also true that we don't really know what
0:45:24.960,0:45:31.360
we're doing at the moment. So there's a[br]lot more research needed to make sure that
0:45:31.360,0:45:38.000
there's no off target effects if you cut[br]out a gene and put in a new sequence. So,
0:45:38.000,0:45:45.280
yeah, no, I don't think we can guarantee[br]that as of yet, but it's it's not
0:45:45.280,0:45:48.888
unthinkable.[br]Herald: All right. Huh, interesting.
0:45:48.888,0:45:56.772
Sounds like the technology isn't there yet[br]for a couple of years or decades.
0:45:56.772,0:46:03.104
Lisette: Oh, well, I think the technology[br]is there, it's just not secure enough.
0:46:03.104,0:46:08.280
Herald: All right. I see.[br]Lisette: So, yeah, it's done in the lab
0:46:08.280,0:46:14.788
big time, but then we don't usually use[br]humans. Only a cell line or yeah.
0:46:14.788,0:46:23.201
Something that is easy to control.[br]Herald: All right. Um, and then a dynamic
0:46:23.201,0:46:31.423
methods for tests, for example, for[br]diseases such as COVID, our target
0:46:31.423,0:46:41.440
tests, for example, the PCR test. Do you[br]think now the testing for infections might
0:46:41.440,0:46:46.400
shift to be more exploratory approaches,[br]for example, through sequencing instead of
0:46:46.400,0:47:00.541
targeted PCR?[br]Lisette: Yeah, that depends if you have a
0:47:00.541,0:47:05.612
suspicion that the infection has reached[br]the bloodstream and you're close to
0:47:05.612,0:47:11.851
sepsis, then it might be your last resort[br]to make a hole. Yeah. Just sequence
0:47:11.851,0:47:18.052
everything that is in the blood, but then[br]you need to be, of course, aware that the
0:47:18.052,0:47:23.059
majority will be human, so you need to[br]filter out a lot. And then what is left,
0:47:23.059,0:47:29.451
you might be able to map to a certain[br]microbe genomes, which are also pretty
0:47:29.451,0:47:38.286
well annotated. So I'm not sure about[br]nasal swabs or something like that, where
0:47:38.286,0:47:46.965
you can find out which flu you have[br]received. So that doesn't really make too
0:47:46.965,0:47:54.277
much sense to me unless you have a good[br]treatment options. But for example,
0:47:54.277,0:48:02.998
tuberculosis is one disease where if you[br]do sequence the germs now more and more
0:48:02.998,0:48:10.553
because a lot of strains of these bacteria[br]have multiple antibiotic resistances.
0:48:10.553,0:48:17.640
And then if you start treating with the[br]wrong antibiotics, you are really screwed.
0:48:17.640,0:48:24.526
So there, yeah, it's already well-[br]established that the university clinics at
0:48:24.526,0:48:29.366
least sequenced the strains before the[br]patient gets treatment.
0:48:29.366,0:48:37.520
Herald: Interesting, yes. Sounds very[br]cool. All right. Thank you so much,
0:48:37.520,0:48:42.080
Lisette. Very inspiring.[br]Lisette: You are welcome.It was a
0:48:42.080,0:48:50.000
pleasure. I hope I could convey the[br]message. Just be aware of, yeah, your
0:48:50.000,0:48:56.080
genes and your data. So yeah, that's[br]that's just there's a lot of potential in
0:48:56.080,0:49:00.800
there. But of course, we shouldn't be. We[br]should not be careless.
0:49:00.800,0:49:04.800
Herald: So, yes, definitely.[br]Lisette: That's all from my side. Thank
0:49:04.800,0:49:09.020
you.[br]Herald: Thank you so much.
0:49:09.020,0:49:16.000
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0:49:18.624,0:49:22.512
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