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Biology Help Desk: Volume 4

Samantha Wright (1324923) writes | more than 2 years ago

User Journal 22

Bring me your curiosity! As before, if this expires and you want to ask a question, just slip me a comment (or an e-mail) and I'll put up another one of these. No question is too trivial; no thinly-veiled troll too transparent! (I'm going to regret saying that, I'm sure.)

Bring me your curiosity! As before, if this expires and you want to ask a question, just slip me a comment (or an e-mail) and I'll put up another one of these. No question is too trivial; no thinly-veiled troll too transparent! (I'm going to regret saying that, I'm sure.)

Sorry! There are no comments related to the filter you selected.

Read lengths (1)

backslashdot (95548) | more than 2 years ago | (#38696022)

Your statement that short ion torrents read lengths are 10x longer than they need to be makes no sense whatsoever. That's true if you are ok with a 4% error rate in the genome .. and missing crucial mutations.

Re:Read lengths (1)

Samantha Wright (1324923) | more than 2 years ago | (#38699428)

I admit that didn't check at the time for the exact length of an IonTorrent read, but the figure given was 200-400x. With the fifth-generation SOLiD system, a read length of just 22 bp is sufficient for human variability and disease identification studies—and coverage solves pretty much all error-related problems. The lab I work in made the decision to go with a SOLiD 5500XL system after about two years of shopping and negotiating with half a dozen different vendors, and the deciding factor was the improvement in chemistry in the latest iteration of the system. (We'd been leaning strongly toward IonTorrent or Illumina prior to that.) Yes, such short read lengths are (even more) useless for targeting repetitive promoter-element-containing regions, but IMHO the IonTorrent read length is still so short that the amount of information gained is not all that useful at its noise threshold. (Feel free to prove me utterly wrong, though; it's probably not hard.)

Bioinformatics for HS Student? (1)

superid (46543) | more than 2 years ago | (#38696222)

Hi and thanks for the offer to answer questions. I'm going to repost something I wrote in the google science fair thread:

Ok slashdotters, I've had no luck getting this question answered elsewhere so I might as well try here. My son is very interested in coding. He's competent in Java and he's picking up c quite well. He's taken an interest in GPU programming and I know over the next year he will do OK with those concepts too (I've been able to get both OpenCL and CUDA code up and running). In other words, we've got the computer end of a sci fair project pretty well established. The problem is that while I know generally what bioinformatics is all about, I have no background or resources in the appropriate biology to help him find a worthy project.

Ideally, what he wants is 1) a bioinformatics problem with a large data set (yes I realize that is redundant by definition) 2) one that would benefit from GPU programming 3) a problem that makes some kind of physical testable prediction that could be tested.

Last year a kid (from Canada?) did a drug interaction study where he took candidate compounds and determined where on a protein they would attach. From that he found two compounds that could mate at the same time because their locations did not interfere. Thus increasing the effectivity. He actually clinically tested "his" drug on cells. Pretty impressive. I'm not expecting my son to reach that level but I'd like to find something real world and challenging that couples computer science with a physical biological process.

any input is greatly appreciated! gary.huntress@gmail.com

Re:Bioinformatics for HS Student? (1)

Samantha Wright (1324923) | more than 2 years ago | (#38699746)

The study you're describing sounds like a fairly challenging task for a student because of the "determined where on a protein they would attach" part. That step alone requires an advanced understanding of chemical kinetics and two or three years of university-level calculus, as well as access to a serious high-performance computing cluster. Because of the calculus requirement, it's generally considered outside of the realm of bioinformatics—it's also something that pharmaceutical companies do religiously as part of drug design. More likely, the information was already available, in which case the study was mostly a question of finding pairs of molecules that would attach separately (an embarrassingly parallel O(n^2) task at worst), and then filtering out combinations that obviously interfered with each other chemically.

As far as tasks for your son, though, unfortunately most biologists don't keep large numbers of these things on hand. :) It sounds, however, that medical work is the right area, because evolutionary biology (the other side of bioinformatics) is much more theoretical. I'd recommend picking up medical journals and reading through some articles with him to see what you can find. On the bright side, almost every problem that doesn't stand to benefit from GPU optimization is simply too small to be worth it, so you should have no trouble tracing something down. If your son is still in high school, also, I'd encourage you to push him into taking every statistics class available; it will help him immensely as his career progresses.

Re:Bioinformatics for HS Student? (1)

superid (46543) | more than 2 years ago | (#38706504)

Thanks for the info. I will try to find some medical journals. We have a family member with Parkinson's so we might start with that. As far as the statistics, yes, he is taking a class and luckily his mom is a statistician :)

what do biologists think of python2-python3 (1)

decora (1710862) | more than 2 years ago | (#38696354)

is everyone clinging to python2 forever?

Re:what do biologists think of python2-python3 (1)

Samantha Wright (1324923) | more than 2 years ago | (#38699478)

I'm not a pythonista, although many bioinformaticians are. As I understand it, the spread of mentalities amongst CS-trained bioinformaticians is the same as amongst any software engineers—some say 'upgrade at once', others are more pragmatic and will write new things in Python 3 but don't bother upgrading old projects as long as Python 2 is supported, and there's a tiny handful of programmers who are happy right where they are in Python 2 and turn off automatic updates whenever they get a chance.

Biologists who just picked up programming out of necessity, on the other hand, are rarely interested in the bleeding edge, and are much more likely to treat code as an extension of themselves, like a pipette or microscope; it's a tool that gets something done and nothing more. Almost universally, biologists with programming skills can be found running old hardware and software until the day it stops ticking.

awesome... thanks (1)

decora (1710862) | more than 2 years ago | (#38701928)

strangely enough i find myself using a text editor from the 1990s.

Re:awesome... thanks (1)

Samantha Wright (1324923) | more than 2 years ago | (#38702822)

That's pretty modern for a text editor. :)

DNA sequencing vs. DNA tests (1)

dkesh (23048) | more than 2 years ago | (#38697654)

There's now a story out that says human genome sequencing could be done rapidly and for about $1,000. I have been trying to get a medical test that's just sequencing a single gene (CPT2). The test takes 4-6 weeks to get results and costs $1100. Do you have any insight why this might be? Is there more work for the single-gene sequencing that doesn't get factored into the full genome price?

Re:DNA sequencing vs. DNA tests (1)

Samantha Wright (1324923) | more than 2 years ago | (#38699556)

That sounds like a combination of cost of labour and older chemistry. The IonTorrent system described was just put on the market and costs $149,000 for the hardware, so it'll be a while before most places have them. Further, for that system, the $1000 price tag is just the cost of the chemical reagents as sold by the manufacturer; the human labour cost is actually pretty substantial. The time requirement does sound a little high, but that probably factors in a processing queue and transit time.

Re:DNA sequencing vs. DNA tests (1)

Ethanol-fueled (1125189) | more than 2 years ago | (#38709222)

I'm not a bio guy, but I'm curious to know what one can learn about themselves using an OpenPCR. [openpcr.org]

Could a layperson, for example, use one to determine their risk of disease with strong genetic factors? A criticism in the Wired article stated that, "The thermal-cycling machine is only a small piece of what's important about PCR and what's required to do it. You need so many other things, including access to chemistry (a reference to proprietary reagents) that's way harder to hack than the machinery itself." What would be the bare minimum of additional items / lab access somebody would need to do it?

Also, mating dance. [slashdot.org]

Re:DNA sequencing vs. DNA tests (1)

Samantha Wright (1324923) | more than 2 years ago | (#38709484)

A thermal cycler does nothing more than heat and cool a little metal block to a series of set temperatures in a short loop, hundreds of times. To perform PCR, you need nucleotide triphosphates (the actual nucleotides that the new strand will be built with), DNA polymerase (the enzyme that performs the actual DNA replication), several different salts in a very precise mixture, perfectly clean water, a micropipette (it sounds like it's from 50s sci-fi but isn't), the extracted DNA (kits for this cost a hundred dollars or so, but are good for a hundred or so reactions), some method of detecting DNA (theoretically doable with a UV light at minimum, but very impractical without ethidium bromide (carcinogenic), a gel box (with a laboratory-grade power supply), and agarose (a starch derived from seaweed)), and a pair of appropriate single-stranded DNA primers, which are how you select the DNA to replicate. It is through selecting DNA to replicate that you turn a normally amplifactory process into a diagnostic one: like a regex, if it's there, you get a lot of it; if it isn't, you get none.

This all being said, there are laypeople who are quite fond of doing this sort of thing. I usually point curious folks here [wikipedia.org] .

(Mating dance is flattering, but not likely to succeed; my girlfriend would be a bit upset.)

Re:DNA sequencing vs. DNA tests (1)

Samantha Wright (1324923) | more than 2 years ago | (#38719680)

Update on this: the IonTorrent system isn't quite released yet, it's coming out later this year. Prior to it, a typical full-exome sequencing job (all the functional parts of genes, like all the code without any headers) costs about $12000, in academia.

Cellular adhesion (0)

Anonymous Coward | more than 2 years ago | (#38698100)

The human body is made of trillions of cells. What keeps these cells together, "stuck" together as it were. Is there a substance on the outer cell wall that keeps them together?

If so, could something be developed to dissolve this and be weaponized? I've always thought about writing a story or something about it heh.

Thanks,

Mike

Re:Cellular adhesion (0)

Anonymous Coward | more than 2 years ago | (#38698426)

Sorry I meant cell membrane. Cell wall is plant cells. I'm a newb.

Re:Cellular adhesion (1)

Samantha Wright (1324923) | more than 2 years ago | (#38699376)

There are a number of different protein families involved in cellular adhesion. They bind, like other proteins, primarily through hydrogen bonding and hydrophobic binding; some of them also require the presence of calcium ions to function properly. This Wikipedia page [wikipedia.org] describes and mentions a number of different examples.

As for the science fiction mechanic: Like most things that can go wrong in the human body, it already exists [wikipedia.org] . (And it's horrible.)

Re:Cellular adhesion (0)

Anonymous Coward | more than 2 years ago | (#38721266)

Awesome. Thanks for the info.

And wow that disease is nightmarish.

Bacteria (1)

DaleGlass (1068434) | more than 2 years ago | (#38767238)

Hi,

I followed with interest the news of the bacteria that can use arsenic. Later (if I understood correctly) it turned out to be less impressive than initially thought, and can only substitute arsenic for a small percentage of the phosphorus it needs.

I was wondering if there have been any attempts to create such bacteria by artificial selection. Is there any sort of targeted effort along those lines to try to determine in what conditions can life exist?

Thanks!

Re:Bacteria (1)

Samantha Wright (1324923) | more than 2 years ago | (#38767710)

I don't know of any such strains personally, but experiments to produce extremophiles certainly exist. (Here's one example [asm.org] : high-pressure E. coli.) A search query like this one [google.com] is probably a good place to start.

This all being said, for us to find life on other planets that exists in some of these forms, there has to be a plausible path backing up the process; I think a lot of people don't quite get this. Just because you can breed, say, extremely radiation-resistant bacteria in a lab doesn't mean that life could evolve from scratch with that much radiation present. (Think of it like trying to assemble a ruggedized computer in the middle of a sandstorm.) There are probably species of bacteria on Earth that could survive on Mars, for example, but unless Mars was once like primitive Earth (it may have been), they never could have evolved there.

Re:Bacteria (1)

DaleGlass (1068434) | more than 2 years ago | (#38770676)

I don't know of any such strains personally, but experiments to produce extremophiles certainly exist. (Here's one example: high-pressure E. coli.) A search query like this one is probably a good place to start.

Cool, thanks

This all being said, for us to find life on other planets that exists in some of these forms, there has to be a plausible path backing up the process; I think a lot of people don't quite get this. Just because you can breed, say, extremely radiation-resistant bacteria in a lab doesn't mean that life could evolve from scratch with that much radiation present. (Think of it like trying to assemble a ruggedized computer in the middle of a sandstorm.)

That makes sense.

But on the other hand, the current atmosphere on Earth is full of oxygen which would be a deadly poison to the life that initially appeared on Earth, if I understood correctly. When we look at a planet with a telescope I don't think we get enough data to figure out what conditions existed in the past. Maybe past conditions were more pleasant, or life managed to develop in a nicer area (like somewhere below the ground) and then migrated outwards.

So is it really that useful to know that an arsenic tolerant bacteria can evolve on Earth? We have a rather specific history here that may not be the only way that produces life, and that's probably quite different from how things go on many other planets.

Speaking of Mars, there was this idea that the experiments performed by the Viking lander may have killed the life it was trying to find. In light of that it seems to me that figuring out which forms of life can exist is probably a good idea, if only to figure out what instruments could be used to try to find it.

Re:Bacteria (1)

Samantha Wright (1324923) | more than 2 years ago | (#38771794)

From a xenobiology standpoint, it's not really that useful to know that arsenic-tolerant bacteria can evolve on Earth, no. It's only a big deal because organisms here have a really bad habit of mistaking it for phosphorus and dying as a result. They have different (but similar) chemical properties, and this can mess up metabolic pathways (series of biochemical reactions) that were finely-tuned for the nature of phosphorus. Phosphorus is a wonderful element, capable of many things, but it's hardly as if life elsewhere couldn't evolve a pathway to distinguish between As and P and use them differently and appropriately.

That being said, there are definitely a lot of reasons a space program would want to know how far our biology can be stretched! It can tell us what we might take advantage of in a terraforming operation, and what kinds of circumstances we can expect contaminants under: there are, for example, some organisms (yeast spores, I think? maybe some others) that can survive direct exposure to all the vacuum, coldness, and high radiation of low earth orbit. That has major consequences for accidentally bringing contaminants to hospitable alien words.
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