Back from Conference!

Brief: The BIBM09 conference was the very first conference I have ever attended. I learned a lot from the various speakers and poster sessions–

I thought it was really interesting how the trend is to now study and manipulate large interaction pathways in silico– a theme of which is the utilization of many different data sources integrating chemical, drug and free text as well as the connection of physical protein interaction pathways and gene expression pathways. There was even a project which dealt with the alignment of pathway graphs (topology).

Dealing with pathways especially by hand and in the form of a picture is probably the bane of many biologists’ existence– I think that the solutions we’ll see in the next few years will turn this task into simple data-in-data-out software components, much like the kind we have to deal with sequence alignments.

And now, back to the real world!

Addendum: My talk went very well :)

And here are my slides with a preview below.

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IEEE BIBM09 Conference – Day 1

Warning: This post is highly non-sequitur– it’s late at night and my brain is full of science.

Wow! I’m learning a lot and having a blast– I’ve met a lot of people and have managed to fill the entire day with workshops and tutorials. The venue is convenient, being right in a hotel (Hyatt).

To be more precise, the conference isn’t really in Washington. It’s in Bethesda.

My talk hasn’t come up yet, but my slides are 100% done– I just have to review them until I start to twitch uncontrollably. Today was the first day filled with talks, so I’m feeling a bit light headed and needing of sleep to digest away all of the information.

One key thing I want to take home to my current project is the use of tetrahedral tessellations called simplices to express protein topology and structure– there’s something very useful about that when searching for regularities and especially when dealing with stability.

Aside from going to workshops, each attendant is asked to fill in a ballot to indicate which of the posters on display are the best of show. We get to nominate three– and I’ve chosen mine for today. For me, it was an easy choice to pick the top two while the last nominee was originally tied. An additional poster show will start on Nov. 3rd.

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Protein Project Progress…

Last week, Liz, Aron, Andrew, Brendan and I sat down to discuss the beta-trefoil project. It was a good chance for me to understand the methods used and the kinds of results we are interested in for my own TIM Barrel project.

Continuing on with the structural repeat problem, I’ll today be writing a short FSA parser that can handle DSSP or DSS output– simply, a very primitive machine will be used to imitate a human’s visual inspection of repeated secondary structural elements in given proteins. This is in line with the work I did manually staring at structures to get a grasp of how to look at protein models, and also in line with the objective to automate much of this work. Prior to that step, I reduced the probability of doing redundant work by using BLASTCLUST and selecting only a few known structures in each cluster to inspect… a sequence based alignment for each cluster will inform me of where my manually detected repeat boundaries map to the remaining sequences.

Oddity: If you BLASTCLUST all the “FULL” (not “SEED”) sets of TIM Barrel sequences for the entire fold from PFAM along with the sequences of known TIM Barrel fold structures of SCOP, you’ll find that cluster fifteen (as of today) has these elements:

1YBE_A A6U5X9 A6WV52 Q2KDT0 Q2YNV6 Q6G0X7 Q6G5H6 Q8UIS9 Q8YEP2 Q92S49 Q98D24 A1UUA2

In the above listing, 1YBE:A (PDB code) is the sole known PDB structure, while the remainder are putative TIM Barrels (uniprot codes) as determined by the HMM model from PFAM.

The enzyme 1YBE looks like this…1YBE_A

It’s an oddity because of the number of alpha-helices inserted within what is usually a hydrophobic beta barrel– the red pieces of ribbon should form a hollow cylinder, but it’s split apart for 1YBE and accommodates a bunch of cyan helices. Labeled in white are helices that break with the beta-alpha repeating secondary structural element (SSE) pattern by occurring before the first repeat. Labeled in green are breaks between beta-alpha SSE patterns.

Reference

Seetharaman, J., Swaminathan, S., Crystal Structure of a Nicotinate phosphoribosyltransferase [To be Published]

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Our Final iGem Wiki (2009)

Link: University of Waterloo iGem 2009 Team Page

The team’s off to the 2009 iGem conference in Boston soon (not me though due to prior engagements). Our wiki was finally finished about a week ago– the wiki is a required objective that iGem teams must produce.

As luck would have it — through all the hustle and bustle of daily busy, I still managed to contribute to the original draft and to the final summary for the poster version of our presentation.

Our wiki pages this year are something to be proud of. It is a stark improvement over last year’s work and the team effort shows through in the varied though unified writing styles and diagrams. The modeling team worked especially well– I’m impressed with the amount of team work just looking through the discussions we had on the Google Group.

There’s a presentation practice today– I wish I could go, but the construction in and around the university is becoming prohibitive… The construction should stop some time around the first snowfall.

Future: Andre has some plans for the modeling team in iGem for the coming year… and I have some interesting ideas for what this team can do in the long run.

3 Chinese Characters

Detour: I was just thinking today that there are three really odd Chinese characters that I wanted to show you. Each of these glyphs are mapped to both spoken Cantonese and Mandarin words but are not generally compatible with everyday speech. For instance, the second word listed below is replaced by the informal “ah(r)3″ sound that Cantonese speakers make at the end of sentences on occasion (varies with situation, personality).

  • 嗎 0×55CE: Audible Question Mark “ma3″
  • 了 0×4E86: Audible Exclamation Mark “lew5″
  • 的 0×7684: Reverse of “of” in English “di(k)6″

The hex code is the position that each character occupies in the big giant unicode table of glyphs for Chinese characters– the integers correspond to relative intonations. These intonations are equally as important as vowel sounds. I really want to learn how to encode human pronunciations using International Phoenetic Alphabet (IPA), but that would be a project for a later day…

Update: In spoken Cantonese, the first word [from the above list] is often replaced by the sound “gwa3″, and the third word may be replaced by “gò3″.

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Phew! Sun Virtualbox Port Forwarding (on NAT) Solution

I finally found a solution for the port forwarding issue I was having with Sun VirtualBox (i.e. NAT provided a weird one-way mapping from which Tin (host) couldn’t dial into TinUbuntu (guest)…) — as far as I understand, this solution is guest operating system neutral but must be configured for each guest handled by a particular installation of Sun VirtualBox. That means that if you’re crazy like me and plan to put your virtual harddrives on USB sticks, you’d probably do just as well to put in a makefile that will do your configurations for you too. So here’s the solution, also saved in my wiki for extra truthiness!

Thanks to Evan and his “justwerks software” blog.

The following commands were issued…

cd /Applications/VirtualBox.app/Contents/MacOS
$VBoxManage setextradata "TinUbuntu" "VBoxInternal/Devices/pcnet/0/LUN#0/Config/guesthttp/Protocol" TCP
$VBoxManage setextradata "TinUbuntu" "VBoxInternal/Devices/pcnet/0/LUN#0/Config/guesthttp/GuestPort" 22
$VBoxManage setextradata "TinUbuntu" "VBoxInternal/Devices/pcnet/0/LUN#0/Config/guesthttp/HostPort" 2222

Which causes TinUbuntu TCP:22 to be forwarded to Tin TCP:2222.

In future, I should remove these rules and re-add them replacing “guesthttp” with my own name for this rule– In his blog, Evan has used a series of names: “guesthttp”, “guestssh” and “guestsql”– In reality, these are actually very good, unambiguous names that I’ll probably end up borrowing.

The one thing I should really dig around for is the meaning of “LUN#0″– it looks like something that’s important– the remaining virtual-directory-like objects in the configuration string look less daunting– “pcnet/0″ is likely referring to the first virtual network adaptor connected to TinUbuntu.

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Redirection is Better!

Brief: Phew! Pointing two URLs to the same doc root apparently can give search engines gas. I’ve thus changed my apache httpd.conf by specifying 301 redirects instead!

#####
<VirtualHost *>
        ServerName tin.blogdns.com
        #DocumentRoot /Volumes/SnO2 ### OLD BEHAVIOUR
        RewriteEngine on
        RewriteRule ^/(.*) http://eddiema.ca/$1 [L,R=301]
</VirtualHost>
#####

Excellent… In case you’re lost, the old behaviour made it so that going to tin.blogdns.com would just forward the content from the server without changing the URL; now the URL is correctly rewritten and content is served first hand from eddiema.ca instead.

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Squishy TIM Barrel Subunits

Again with the TIM Barrel pictures! Here’s some text about it from my notes…

1a5m (A Urease) is a really interesting protein– it consists of three subunits. Each subunit consists of three unique domains: a very squashed TIM Barrel, an alpha-alpha-alpha-beta-beta domain and a beta-beta-alpha-beta-beta domain. I’m not yet sure what to call little broken alpha helices that have less than two complete turns. The TIM Barrel (though exceedingly asymmetrical) will still be accounted for in the data to be analyzed. The TIM Barrel (566 amino acids) is the alpha subunit of each symmetrical subunit. The remaining two domains are the alpha and beta subunit though PDB is not clear which is which: they each weigh in at 100 and 101 amino acids. 1a5m is part of several solved urease structures in the PDB– the collection: {1A5K, 1A5L, 1A5M, 1A5N, 1A5O} are solved by Pearson et al. (1998).

References
Matthew A. Pearson, Ruth A. Schaller, Linda Overbye Michel, P. Andrew Karplus, and, Robert P. Hausinger (1998). Chemical Rescue of Klebsiella aerogenes Urease Variants Lacking the Carbamylated-Lysine Nickel Ligand. Biochemistry. 37(17):6214-20.

Squishy squishy shapes– the giant pink object in the next picture is actually three such TIM Barrels, each of which belongs to one of the three subunits.
1a5m_holo
Each of the three subunits are shown separately below…

1a5m_1_3 1a5m_2_3 1a5m_3_3

Aesthetically pleasing– these images were captured from the JMol output available from RCSB PDB.

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T.A.ing — half of the semester done!

Wow, it’s been half the semester already. It’s been a good experience so far. This job has highlighted two key things I should work on though. First, it’s impossible to know everything that can be asked in a given tutorial, so I should figure out what the boundaries for the module are (i.e. what the current module does not approach), and know the most likely places the answers are in the textbook so I can refer to an official explanation when I’ve drawn a blank. Providing answers that go beyond the scope of a course is actually harmful since it affects students’ recall during examinations! Second, I need to reduce the amount of repetition I use to explain something. Specifically, saying the same sentence twice doesn’t help comprehension– clearly, there’s something incompatible about that sentence.

Overall though, I’m happy with how the tutorials are progressing and how our (my and Ariana’s) introductory slide shows go– The quizzes at the end of class have progressed into being a very smooth transaction too.

In about half an hour, I have to head down to watch them all write a midterm along with the other TAs.

Applications for Winter TA positions are due soon.

It might be nice to do a hands-on laboratory course next, but tutorials are certainly pleasant.

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The Return of Phi C31

I’ve been so out of the loop with iGEM over the last month. I’ll need to figure out how to get back into the swing of things, probably starting with the post mortem meeting on Tuesday. Generally, since no new maths could be put on the table that actually encompassed the problem well– the brute force approach was kicked into high gear with a few more filters to increase the probability of success.

Call these “System Filters” since they aren’t really based on biologically significant concepts, really just sanity checks that are conceptually consistent with the project (i.e. we’d run out of hard disk space otherwise…). Significantly, Matthew implemented “Blank Stare”, which destroys reactants that exceed a given length (thus preventing them from hogging the CPU looking for less parsimonious solutions). Less significant were Andre’s “Lone Gunman” which deletes arbitrary chromosomes with stochastic efficiency and my “Tag” which prevents chromosomes from cross reacting.

(On second thought, “Tag” IS a “Biological Filter” not a “System Filter” because it removes redundancy by implementing the rule that we only admit bacteria that have exactly one chromosome.)

I should mention that “significance” above isn’t about the triviality of the code, it’s about the amount of anticipated efficiency boon we’d gain from an item’s deployment.

Tomorrow’s post mortem will continue the work I’ve started on our iGEM 2009 Wiki Modelling page… We’ll decide what we want to mention, how close we got to our solution and figure out how to precisely characterize the problem space uncovered by our various attempts.

Additionally, we should probably discuss the relevance of John’s attN site cloning and tests to see if the operators show any sign of degeneracy, and which ones in particular.

Finally, I should mention that Brandon has been working on a C++ port of the whole application we wrote in Python to elucidate how much the virtual machine impacted the performance of our solver– the team is quite divided on this idea with a big half (myself included) thinking that the exponential growth due to the algorithm is the greater factor– Brandon may have some answers for us when it’s up and running.

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