Thoughts on Special Relativity

If I pursue a beam of light with the velocity c (velocity of light in a vacuum), I should observe such a beam of light as a spatially oscillatory electromagnetic field at rest.  However, there seems to be no such thing, whether on the basis of experience or according to Maxwell’s equations.  From the very beginning it appeared to me intuitively clear that, judged from the standpoint of such an observer, everything would have to happen according to the same laws as for an observer who, relative to the earth, was at rest.  For how, otherwise, should the first observer know, i.e., be able to determine, that he is in a state of fast uniform motion?  One sees that in this paradox the germ of the special relativity theory is already contained.  Today everyone knows, of course, that all attempts to clarify this paradox satisfactorily were condemned to failure as long as the axiom of the absolute character of time, viz., of a simultaneous, unrecognizedly was anchored in the unconscious.  Clearly to recognize this axiom and its arbitrary character really implies already the solution to the problem.

…thought 16 year old Albert Einstein as he scribbled it down in his notebook.

Making whole exome and whole genome sequencing data files really, really, ridiculously smaller.

Recently I’ve been doing some genomics work, using whole genome sequencing (WGS) and whole exome sequencing (WES) data provided by the Alzheimer’s Disease Sequencing Project (ADSP). The goal of this project is to identify DNA variants contributing to early and late onset dementia, and to isolate potentially neuroprotective rare variants and single nucleotide polymorphisms.

I’ve done a bit of genomics analyses in the past, from pre-processed datasets. However this is my first real foray into the thick of genomics big-data; and I’ve made a few observations I’d like to share, including how we shrunk a 70 GB dataset into a 900 MB text file, without losing any information. I will get to those in a minute. First, I just want to say that more people need to jump onto the Alzheimer’s genomics bandwagon, which is currently passing through the wild-west. It is nowhere near the state of cancer genomics. You may be thinking – ‘rightly so. cancer is a much bigger problem’; and it probably is. But to summarize the AD problem:

  • If you live long enough, you will get Alzheimer’s

On the plus side, there now exists a pretty massive AD sequencing dataset. It includes the genomes of over 5000 Alzheimer’s disease (AD) patients and 8000 age-matched (or older) controls. The data is housed at The National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS). To get this data one needs an eRA commons login, a dbGaP repository key (files are encrypted), and the SRA Toolkit to retrieve and decrypt files from dbGaP.

  • Genotype Data: raw sequencing read and mapping BAM files stored in SRA format, along with QC genotypes in PLINK and variant call format (VCF).
  • Phenotype Data: phenotypic information from consented study subjects and family members, and pedigree records of genealogical relationships.

Based on the phenotype data, we identified a handful of individuals over 90 years old with known risk factors for AD, who somehow escaped developing any symptoms of dementia. For example on chromosome 19 there is a gene called APOE; the ε4 allele of these gene is linked to late-onset AD. APOE codes for a protein that assists in the biosynthesis of apolipoprotein E, a cholesterol transporter that aggregates and clears amyloid deposits in the brain. Reduced function of this gene results in beta-amyloid plaque build-up, a highly marker highly correlated with AD. The ε4 allele is a well documented risk factor of AD, and the incidence of AD is 10-fold higher in patients with the double variant, APOE 4/4, than in those with the single variant. Indeed this is reflected in the ADSP dataset. However, there is a small cohort of individuals over 90 years old who had the APOE 4/4 allele with no psychological or physical symptoms, confirmed by interview and autopsy.

  • What protected these people with APOE 4/4 allele from getting Alzheimer’s Disease?

Perhaps there’s a common genetic thread. Next step: acquire gene sequencing data from ADSP…

I just need to download a mere 190 GB of text data. That’s absurd. Mind you these are just the files for single nucleotide polymorphisms are rare variants. I downloaded the smallest one to find out what on earth is going on in there.

 

There is a variant in every row and a person in every column – yeep. It doesn’t make sense to format the data this way, given rare variants are rare. Also, I don’t care when someone doesn’t have a variant (0/0) or a low quality read (./.) at a particular location (maybe for some back-alley pileup statistics). I only want to know if a person did have a variant at a particular location.

Let’s fire up perl and put those instances in another file. I think the best way to format this data is to put everyone who had a variant on the same row.

Let’s see if this lossless conversion saves any space…

ALL_SPARSE_FILES_c1.tar.gz 19-Jan-2017 23:27 2.9G
ALL_SPARSE_FILES_c2.tar.gz 19-Jan-2017 20:50 701M
ALL_SPARSE_FILES_c3.tar.gz 19-Jan-2017 20:55 280M
ALL_SPARSE_FILES_c4.tar.gz 19-Jan-2017 20:56 99M
ALL_SPARSE_FILES_c5.tar.gz 19-Jan-2017 20:57 613M
ALL_SPARSE_FILES_c6.tar.gz 19-Jan-2017 21:01 334M

Wow, that 70 GB file is now 2.9 GB.

More to come…

The Sense of Self Illusion

Someone recently posted this on reddit…

Tonight, I discovered that I am afraid of death. Never, before tonight, had I been truly afraid of it. Of course, it’s not a fun thing to think of, but I don’t know, it never really hit me as something to fear. I would sometimes think about what kind of impact I had made on the world and what effect my death would have made, but that never resulted into something. I’m a fairly happy person. I am a healthy nineteen year old. I don’t drink, I don’t smoke and don’t do any sort of tobacco. I feel that if I stick with this philosophy, I will help someone make better decisions. I want to be someone people look up to. I enjoy having a good reputation. I care for others. I have sympathy and empathy for others. I am saying this now because I don’t ever really hear it from anyone, but I hope to believe it’s true and I’m not lying to myself. Anyways, tonight I was leaving my friend’s house and they were drinking a little bit, and of course I don’t condone it, but I’m not gonna judge them for it. I’m there so that they don’t do anything stupid. So, after awhile, I decide the night is starting to end. My friends started watching a movie and I felt that I should get home. I grabbed my coat, said a subtle goodbye and left. As I’m driving along a backroad I start going up a slight hill and see a glow of carlights right over it. I tend to drive closer to the middle of backroads for safety (there was snow on the sides of the street). Anyways, since I saw the glow of the lights I shift over a little bit to make sure that I am in my lane. Then coming over the hill, right in the middle of the road, was a speeding vehicle. I knew the vehicle and the person driving, as I had just left the neighborhood that they live in. I went to high school with this person and I know that they have a history of drinking and not making great decisions. I can’t prove that they were drinking and driving, but it was late, around 1:30 am, and it was the weekend. Regardless the person was easily going 50 mph over the speed limit. The person comes very close to hitting me. I quickly move even more towards the side of the road and the car misses me. The speeding car would’ve absolutely mutilated me and my car. As I look in my rearview mirror I see the car’s breaklights turn on as they knew it was a close call. I continue on the road and start thinking about what if the person had hit me. Would I be dead? Paralyzed? Would the other driver be dead? With my adrenaline pumping, I take deep breaths and continue driving, but much slower, about 5 mph under the speed limit. I continue to think about what happened I think about my impact on the world. Have I done enough with my life to be satisfied or to have left a legacy? All I could picture was newspaper article. I don’t know why, but I started to feel scared. I don’t want to die. I don’t want to leave my family and friends. I love living. If I had died, how would it have effected my family and maybe even worse, what if I had survived this incubus. I saw myslef living a sadder life. I’d forgive the other person so that they wouldn’t have to live in pain, in hopes that they wouldn’t feel bad. I couldn’t imagine my life being the same. I thought prior to this experience that I had been living life more than others. I considered myself a good person, but what did I have to prove it? Nothing really, maybe some stories from friends and family, but who would speak highly of me other than my family and friends? What kind of person would the news article say I was? This experience has changed the way I’m looking at life. It kind of amazes me that an experience like this motivated me to write these thoughts. I believe I needed this to help me life a fuller life. I feel like I’m just reiterating, now and a lot of it’s corny, but it’s true. Tonight, I discovered that I’m affraid of death and what my death would entail. I just wanted to share this story. I don’t know if I’ll ever tell my friends or family, but I will push to be a better person and help others make better decisions. Thank you for reading this. This was my revelation.

The post had zero comments, so I decided to indulge. Here is my reply…

I can sympathize with your revelation. The very clear and lucid fear of death washes over me every once in a while. I’ve used various coping strategies over the years to deal with this unfortunate certainty.

The simplest is to just think about something else, immediately. There is no reason to deeply ponder death while you’re in a fear-of-death state of mind. And it is really easy to engage in something else; something as simple as opening reddit is enough to move on.

Another more complex coping mechanism I’ve developed is to convince myself that sense-of-self is an illusion. There is no such thing as “you”. Every day we are someone different. Our old “self” dies every moment, and a new “self” is born in the next. Imagine you have a terminal illness, but we have the technology to perfectly load your brain onto a robot. Everyone who has ever done this procedure swears it works – they feel precisely like the same person they were just prior to the transfer. Seems like a great way to live forever.

But what if the person (the human) was allowed to continue living after the transfer? Is there now two beings with an identical sense of self? Is there two… of ‘you’? If not, which one, the human or the robot, would be your host? What would you think if you woke up still in the human body, but the robot claims they are definitely the real ‘you’? What would you think if you woke up in the robot body? What if the human form was terminated during a successful transfer – was there still a person in that body that died? My answer is that self of self is an illusion, loosely formulated by a combination of memories, consciousness, attention, and an ongoing stream of sensory perceptions. For me, framing the concept of self as a fleeting moment helps mitigate fear of any death some future self will experience. I feel for that person, but it wont be me.

Lastly, a more profound and uplifting coping mechanism I use is to reflect on the awe of the universe, and existence itself. There could have easily been no universe – nothing. It’s curious to think about why anything exist at whatsoever? Why the fuck does the universe exist? And its rules are crazy. Time is relative, it can be sped up or slowed down. Time becomes warped around matter (objects with mass). Time stops at the event horizon of a black hole. A massive black hole might lead to a different universe. Another universe? Gravity pulls things together, but we have no idea what gravity is or how it does what it does. Photons travel at the speed of time. All electrons in the universe might be just one single electron moving back and forth through time. Sometimes antimatter jumps into existence, out of some parallel plane of existence. Any given vector in the vacuum void of space has some probability of generating a particle from what appears to be nothing whatsoever. Random collisions between elementary particles governed by the arbitrary laws of this universe sprouted ‘life’, and soon after a beings with metacognitive faculties. This being is strangely close synthesizing artificial life with intelligence exceeding its own cognitive faculties. Entities smarter than humans will soon be creating even smarter versions of themselves, and worlds. These worlds could be simulated on a computer, and those worlds could contain worlds of their own. Our universe could be such a simulation. Any unfathomable thing is possible. It may have already happened and it may happen again; or all possible things are happening right now, simultaneously. The universe is a grand and wondrous thing. There is absolutely no telling what comes after death, and even if it comes trillions of years from now, it will feel like a blink of an eye.