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Posts Tagged bioinformatics

What does a chromosome look like? (Not Just DNA #2) Grant Jacobs Nov 14

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Aside from the fun of peering at the stuff that codes for the parts that make up us, knowing how a chromosome is arranged inside a cell nucleus might tell us a lot about how our genes work. Understanding the structures of genomes might well be what is needed to make sense of the genetics of complex diseases.

So just what does a chromosome look like?

Are our genomes stuffed into the cell nucleus like loose string jammed into a bag or are they arranged in an organised way? Is the arrangement of genes that are being used in the cell different from those that are not being used? Are genes that are controlled in similar ways near each other? Do different chromosomes interact with eachother?

Mitotic chromosomes (via: The Pavellas Perspective)

Mitotic chromosomes (via: The Pavellas Perspective)

You’ll have seen images of chromosomes looking like two rods pinched together in the middle, like in the electron micrograph to the right, or perhaps as part of a karyotype (karyogram or idiogram)- showing the collection of chromosomes in your cell stained to revealed a banding pattern shown below.

 

Karyotype of person with Down Syndrome - note the extra chromosome 21 (See Footnote 1 for more).

Karyotype of person with Down Syndrome – note the extra chromosome 21 (See Footnote 1 for more).

Karyotypes, like that of a person with Down syndrome below, are typically used to investigate loss of large parts of chromosomes (deletions), or swops of large portions between chromosomes (rearrangements), that can be associated with different diseases or syndromes. Small changes can happen and affect genetics, too, but are too small to be seen this way.

Chromosomes can also change shape, depending on what genes are being used and what stage in the cell’s lifecycle they are in.

Just like us, our cells have a lifecycle, growing and producing offspring (daughter cells[2]). The chromosomes seen in karyotypes and the classic ‘X’ are from cells that are from cells about to divide into two daughter cells. In this stage of a cell’s lifecycle, chromosomes aren’t doing the work of a growing cell, but are tightly packed and aligned up against each other ready to be pulled apart into the two daughter cells.[3] (Also, these cells have been broken apart so that the chromosomes can float free.)

During the ‘growth’ part of the cell cycle, the cell does the chemistry that type of cell gets up to. If you were to look down a microscope into these cel, you couldn’t see how chromosomes are organised, even if you added chemicals that stain DNA or the packaging proteins (histones) that our DNA is wrapped around. What you’d see is an opaque mess that you couldn’t make much sense of.

Staining for specific features can tell scientists if those features are near the edge (periphery) of the nucleus or the middle, or if the features seem to be clustered together inside the nucleus, but you couldn’t really make sense a whole chromosome this way, it’s just too confusing.

This is a classic problem in science: trying to create a picture of something you can’t see or make sense of directly.

What to do then?

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Computer modellers for the win Grant Jacobs Oct 10

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As a computational biologist I rather like the look of this year’s Nobel Prize for Chemistry – it’s been awarded for contributions to computational modelling, to Martin Karplus (University de Strasbourg/Harvard), Michael Levitt (Standford) and Arieh Warshel (University of Southern California).

Molecular modelling takes several forms. The twist in the work the prize has been awarded for is multi-scale modelling, in their case bridging classical (Newtonian) and quantum modelling.

Take a ball. Given the forces on the ball you can apply the ‘classical’ physics of Sir Isaac Newton (and those that furthered his work) to determine where the ball will be at a given time in the (near) future. That’s Newtonian modelling.

Peter Murray-Rust, CC 2.5. Source: Wikimedia Commons.

Peter Murray-Rust, CC 2.5. Source: Wikimedia.

We can think of molecules—chemicals of several atoms or many more—as balls connected by sticks, chemical bonds.

To the right is a ball-and-stick model of a single amino acid, proline.

If you can treat atoms in a molecule as balls, you can apply Newtonian physics to them.

Atoms are joined to each other by chemical bonds. Different types of bonds have different rotational properties. Some rotate freely, others less so. So we can add rotational properties to our model.

There’s the different forces atoms have on eachother. We can simplify these to something like compressing springs that draw together or push apart atoms or groups that attract or repel eachother.

Keep going and we can built up a method to simulate the motion of molecules.

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Blogimmuniqué: titles and series (and Not Just DNA #0) Grant Jacobs Sep 12

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Blogimmuniqués are my irregular commmuniqués about Code for life.

Over the next few weeks you’ll notice a few changes in the titles of posts, identifying the intended audience of different articles.

Briefly,

  • Articles ending in (Not Just DNA #1), with an appropriate post number in place of ‘1’, are part of an irregular series of sorts on how our genomes that make our genomes work. The first post will be Is a genome enough (Not Just DNA #1). This isn’t a series in the true sense, but rather a theme – posts for it are likely to be irregular and the topic is taken in it’s broadest sense. Most articles in it will aimed at non-specialists – that is, everyone. More thoughts on this series in Not Just DNA #0, below.
  • Articles intended for bioinformatics scientists will start with Bioinformatics: just as my previous post did: Bioinformatics: WikiProject computational biology competition 2013.
  • Articles with neither a specialist focus nor a particular topical focus will have titles without appellations.

I may introduce other themes later.

Why not separate blogs?

Most people set up separate blogs for separate themes or focuses and I’d agree it usually is the best idea. Part of the reason I’m not opting for this, aside from avoiding managing several blogs, is that I like the idea of showing more than a narrow focus on one thing.[1]

I suspect most of what non-scientists see of scientists on-line are them talking about their speciality or things close to it. It must look incredibly narrow-minded.

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Bioinformatics: WikiProject computational biology competition 2013 Grant Jacobs Sep 10

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This competition might be a way to put your course assignment or thesis introduction to good use and be in with a chance to win,

  • 1st prize – $500 (USD) and 1 year membership to the ISCB.
  • 2nd prize – $250 (USD) and 1 year membership to the ISCB.
  • 3rd prize – $150 (USD) and 1 year membership to the ISCB.

The competition is part of an ISCB (International Society for Computational Biology) aim to “further its mission by increasing the quality of Wikipedia articles about computational biology, and by improving accessibility to this information via Wikipedia. The competition is open to students and trainees at any level either as individuals or as groups.”

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Alternative bioinformatics Grant Jacobs Jul 04

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There’s alternative ‘medicine’, then there’s alternative bioinformatics.

Those who aren’t computational biologists / bioinformaticists should proceed no further. You really won’t get these, they’re way too in-house. You really need do to know something of the tools to make sense of them. But that’s also the beauty of it.

I’ve just selected a few, more-or-less in chronological order; check the original source for more. As you can see we owe this to Mick Watson (get past the first few, they’re to introduce theme):

After my shamtools tweet yesterday, I’m going to start a new hashtag:

Shamtools: software that pretends to do everything Samtools does, but actually does nothing

BEDRules: software that encourages you to go to bed every time you try and figure out which command in BEDTools you need

NoTie: the aligner that just prints NO

TooPHat: the splice aware aligner for when your data set is just PHAT

REMEMBOSS: software utility that periodically reminds you of the existence of EMBOSS

WHAMtools: a tool for converting sequence to 80s pop music

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More winning science reading Grant Jacobs May 15

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I’d like to return to writing ‘proper’ posts, both for general readers and scientists. But there’s a lack of this thing called free time—I think it’s called that, I’ve forgotten—that’s getting in the way.

Readers could try the winners of the inaugural Science Seeker Awards. Don’t ask me how 3 judges whittle down over 350 entries to a bit over a dozen winners. You can browse the full list of nominations too. Go for it. Good reading for free!

Some of my older writing is under my Writing page. (Another thing long due for an update or, realistically, more content for it.)

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Nature’s reproducibility effort: when to get data specialists on board Grant Jacobs Apr 27

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Scientific magazine Nature has announced an initiative to aimed at aiding the reproducibility of biological research papers. They’re planning to expand the methods section to cater for this, introducing a checklist and offering a Protocol Exchange site.

I’d like to draw attention to one point ArsTechnica’s coverage of this development noted that has wider impact, outside of this Nature initiative:*

To let certain readers know exactly how likely a given result is, Nature will now provide the authors with a statistician to consult (which, really, they should have arranged for themselves before even writing the paper). Authors will be encouraged to provide the underlying data for any charts or graphs in the paper.

This is too late in the act for the research, although understandable from what Nature is trying to achieve for itself and the relationship with the wider public.

The time to start getting the statistician, the computational biologist or other ‘data’ specialist involved isn’t before writing the paper or even when you start the work, as one commenter there wrote, but when you write the grant application.

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Epigenetic dynamics – free Grant Jacobs Mar 15

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Those with interests in epigenetics and genome structure may want to check out Nature Structural and Molecular Biology’s focus on epigenetic dynamics. (This gives me an opportunity to briefly sound off on a favourite topic…)

One fascinating development over the past few years has been explorations of the three-dimensional nature of genomes, how they are arranged within the nucleus of our cells, how the spatial organisation of genomes might affect how genes are used, interactions between parts of our genomes and far, far too many other questions…

I guess you could say you know an interesting area of science by the questions it raises.

Yeast genome model. From Duan et al, Nature, 2010.

Yeast genome model. From Duan et al, Nature, 2010.

As a student, I studied proteins that bind DNA and the protein-DNA interactions they make. I’m still interested in that—old interests don’t die that easily in science—but these things now fall within a wide range of aspects.

Although a relatively short list of reviews, the focus on epigenetic dynamics covers an interesting range of topics that illustrate how studying gene regulation have moved from simple beginnings of the immediate promoter and protein binding sites in DNA of the 1980s (or so) to the rich complexity of DNA and histone modifications, nucleosome (re-)positioning, protein complexes, chromatin loops, chromosomal domains, regulatory RNAs and more.*

Particularly appealing is that all of the articles are free for anyone to read.**

(Original from Luger lab, sourced from Biomedical Beat.)

(Original from Luger lab, sourced from Biomedical Beat.)

Speaking for myself, it’s great to see a more ‘spatial’ thinking about genomes emerge in molecular biology over the past few years. One of the appealing things about 3-D genome structure work (to me) is that it shifts whole genomes into computational structural biology rather than the more ‘linear’ approach typical of the current genome projects.***

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Structured procrastination, 2 Dec 2012 Grant Jacobs Dec 03

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Another edition of my irregular structured procrastination reading lists – have fun exploring these. (Geekier ones nearer the end.)

Sci-fi movie

Geneticist Ricki Lewis offers a review of Jim, which she says is more compelling than GATTACA. The movie can be viewed on-line. (If you watch it, let me know what you think.)

Gene-based dating

You think gene-based dating in sci-fi? It’s already with us. See also this twitter conversation. (There’s also a service that matches dates by their dogs.)

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Sea stars and mosaics Grant Jacobs Nov 29

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At first you wonder if this sea star is real. It looks more like a kid’s geometric doodle from a distracted afternoon at school than an animal.[1]

Click on image for source; Creative Commons Attribution-Noncommercial-Share Alike 3.0 license

The World Asteriodea Database indicates Iconaster longimanus was first described in 1859. (The photo above was taken by Dieter in the Philippines in February 2007.)

(Source: Wikimeda, pubic domain.)

Among the later descriptions in the Asteriodea Database entries are ones from the famous HMS Challenger voyage.

To most today the name Challenger recalls the space shuttle that horrifically broke up little over a minute into it’s flight and brought a temporary halt to the shuttle program. The shuttle Challenger was named after the HMS Challenger, whose voyage was a grand British scientific survey of it’s day.[2]

Unlike the short life of the ill-fated space-farer, HMS Challenger’s voyage spanned over several years, 1872-1876 and travelled the world.

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