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Tinypliny's Journal

tinypliny
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07/10/2008 17:51 #44920

Linkage Disequilibrium Blocks/Triangles
Category: science
I just had a zen moment in the interpretation of Linkage Disequilibrium Maps. (Also called LD maps, LD blocks, LD triangles - take your pick.) Turns out I was actually sweating 1st grade stuff!

I found that NO ONE explains this EXTRAORDINARILY SIMPLE thing in their umpteen papers, reviews, tutorials and what-nots. I just want to post this here so that when people google this simple little question, they find an equally simple and straight-forward answer!

This is an example of what a very small section of a Linkage Disequilibrium Map or an LD Map looks like.
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Concentrate on the upper part of the map.
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The thick blue line represents a strand of a chromosome. The white bars on the blue line of the chromosome are SNPs (Single Nucleotide Polymorphisms) that have been identified and sequenced. This means that we know what initial Nucleotide base has morphed into what final Nucleotide base. (Thus making it a polymorphic locus - or a position on the chromosome that exists in more than one form. The two forms are the intial nucleotide base and the final nucleotide base.)

These SNP locations or loci are labeled in this picture as 1, 2, 3, ... and so on. Each of these SNPs has a name that starts with rsXXXXX where XXXXX is some numeric code. Each SNP is represented by a labeled grey triangle below the thick blue line (the chromosome).
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The purpose of an LD map is to tell us whether any two given SNPs are INHERITED TOGETHER in an offspring. In other words, we want to know if any two given SNPs are in Linkage Disequilibrium.

An example: Are say, SNP #5 and SNP #9 in linkage disequilibrium? You trace down the column leading from grey triangle #5 or SNP#5 (Name: rs2299433) going toward SNP #9 (rs2237717). Do the same for SNP #9 going toward SNP #5.
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The square in which the columns leading from SNP #5 and SNP #9 intersect is the one you should focus on. I have encircled it above. As you can see its a LIGHT RED and has a number, 75. Thus SNP#5 and SNP #9 have a correlation of 0.75 and are in fairly high linkage disequilibrium with each other.

In simple terms, if your square of focus is a deep red, then the two SNPs you are interested in have the highest correlation with each other and have a highest Linkage Disequilibrium. Thus, one of them can easily act as a proxy for another. The lighter the shade of red, the lesser is the correlation between the two SNPs. For example, SNP #5 and SNP #7 have a low correlation (0.32) with each other. Thus, you cannot reliably take SNP #5 and say that it could possibly act as a proxy for SNP #7.

LD Maps also tell us about HAPLOTYPE blocks. See the blocks labeled, "Block 1 (49kb)", "Block 2 (23kb)", "Block 3 (93kb)" ... and so on.
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These triangles or the blocks of dark red represent SNPs that are all in high linkage disequilibrium with each other and thus are all inherited together. They are also on the same section of the chromosome. These SNPs form a HAPLOTYPE. Every big red triangle or block in the LD map indicates a HAPLOTYPE on the corresponding stretch of the chromosome above. You only need to look at one or maximum a couple SNPs in a haplotype to know about the fate of the entire section of the chromosome that forms a Haplotype. It saves money and time.

The HapMap Consortium project has painstakingly constructed such an LD map for each and every known SNP in the entire human genome. Their LD maps look somewhat like this (using the haploview software: )

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Though it is complicated, if you followed the simple tutorial above, you should be able to make sense of even complicated maps such as these. You are most welcome to leave a comment or drop me an email if you need further clarification!

I don't care who is laughing at this ridiculously detailed explanation of a kindergarten concept in genetics and genomics. Personally, I am just EXTREMELY relieved to finally know it well enough to be able to explain it. :)
YesThatCasey - 03/26/14 00:18
What a cool little slice to pop up. I need to read this later
raddna - 03/26/14 00:10
Awesome explanation. Totally simplified.
tinypliny - 07/10/08 21:47
Wow!! You should totally apply! You'd make an awesome Epidemiologist!! Let me know if I can propel your thoughts a bit more toward Epi. I think (e:boxerboi) is seriously considering Epi as well. The future is in Genetic/Molecular Epi and population studies.
terry - 07/10/08 21:21
More and more I think this may be where I am heading... From chemistry to biology to biochemistry to microbiology to genetic epidemiology...seems logical to me.

Can't wait to join you.
tinypliny - 07/10/08 20:48
That's funny, (e:heidi). :)
Thanks for commenting! Just to make it a bit more clear, I think I should add a simplified explanation of why exactly its called Linkage Disequilibrium when two SNPs are inherited together. The first part is easy. The SNPs are linked together on the same chromosome-> hence "Linkage". It's a disequilibrium because if they had not been linked together (or had been independent of each other), the offspring would be as likely to not inherit the two SNPs together as they would be to inherit them together. So there would be a 50/50 chance of getting them together or not getting them together, from the parents. Thus, if you examined a huge number of offspring and looked to see whether they have any two independent/unlinked SNPs, you would find an equilibrium between the condition of inheriting the two SNPs together and the condition of inheriting only one of the SNPs.

A more rigorous and mathematical explanation of the above is called the Hardy-Weinberg Equilibrium/Principle/Law in Genetics. :::link:::
heidi - 07/10/08 19:27
Wow, Tiny! That's really cool. Not that I'd ever heard of linkage disequilibrium before just now... but learning the word "disequilibrium" alone was worth reading this. :-)

07/09/2008 20:40 #44915

Nifty Research Tools and Software
Category: i-tech
I found a host of nifty and useful research tools out there that are totally worth sharing multiple times. These might be just the life-savers, organizers and new-idea germinators that graduate students and serious researchers are looking for. Can't guarantee that they would make your life easier though...

1. Keep tabs on what's happening in the peer-reviewed research world. From the website:
Discussing and Creating Peer-Reviewed Research: Research Blogging

Do you like to read about new developments in science and other fields? Are you tired of "science by press release"? Research Blogging is your place. Research Blogging allows readers to easily find blog posts about serious peer-reviewed research, instead of just news reports and press releases.


The RSS feed is here:

The real question is however, just how many RSS feeds can one read before it turns into an unmanageable information overload and just becomes toxic??

2. Making a Checklist and sticking to it: The Tada list

It has a very simple interface that I use to make a checklist of things I need to do everyday. Finishing the tasks on the list actually is very satisfying. I find that the more I use it, the more disciplined I want to be in my reading and work goals. I know I can very well make lists on paper. But if I use an online interface (a) I don't have to worry about losing my lists, (b) I can access and tick off my list from anywhere (Well, almost. Any place that has net access). (c) Save paper! (d) copy out the list if I need to be in a really remote location, or maybe a conference.

3. An excellent comparison of Reference Managers: This is an exhaustive wiki about all the reference managers out there. Some of them are free, web-based and help you access your references anywhere and anytime. The next time that dreaded hard-disk crash happens or worse, your laptop or USB drive gets stolen, you don't have to worry about your dissertation references anymore. I currently use RefWorks - that is free via my University and via Roswell. However, I am actively exploring other free and open-source alternatives such as:
-- Connotea from the Nature Publishing Group ->
-- Zotero - a Firefox Extension for Reference Management ->


4. Synchronizing Notes, PDF Annotations, Anywhere, Anytime: Note-Taking Software Comparison: If you print out PDFs just because you can't mark them up online/on-screen, there is help! By using some of these FREE note-taking software you can mark and highlight those PDFs on-screen, avoid all that paper clutter and save all those reams of paper (and trees). I currently use Jarnal - a platform-independent, open-source, free Java-based note-taking software ->

Options. Options. So many Options.
tinypliny - 07/09/08 23:04
It's interesting you say that because that very thought is also related in a tangential way to the future of the tissue repository at Roswell. They are planning to set up microarray libraries for all the breast tumour tissue they have in the repository. Microarrays are an indepth analysis of the DNA/RNA (and thus potentially proteins) that a tumour generates. This is called the expression profile of the tumours.

These DNA, RNA and proteins (expression profile) make up the tumour's "signature". Thus, a microarray might be used to recognize a tumour and classify it on the basis of its signature DNA/RNA and proteins (or expression profile). However, tumours have a lot of DNA and produce tons and tons of various RNA sequences (and thus proteins) and their expression profiles can be mind boggling. As we speak, new expression profiles are probably being discovered and characterised.

The problem is not every RNA sequence produced by these tumours can be profiled because of the huge amount of effort and cost involved in building a microarray library that is so detailed as to included every RNA sequence ever discovered. So the researchers now have to pick and choose what DNA/RNA sequences are the most relevant for the classification of the breast tumours and would most likely be used by investigators in their future research. This is necessary to cut down the costs. Also, we have limited amount of tissue and not an endless quantity. Hence, the need for careful consideration.

The dilemma is, research is evolving so rapidly that we cannot possibly know if the profiles that are used to classify tumours today will still be relevant tomorrow. I wonder how we will decide what goes into the microarray library. Would it still be useful, say ten years from now? Would we have wasted all the money to drill for so much information and yet be faced with a lack of information some years down the line? The meeting is next week. The decisions that will be made will be very crucial to the future of tissue-based research at Roswell. And it will all boil down to one question: How much information could we possibly afford today so that it might be helpful tomorrow?
paul - 07/09/08 22:19
I think about this all the time. At work we will be intergrating some blogging technology I am developing into the new intranet. It is hard to tell what happens when there is too much info. Luckily, computers are good at sorting and searching and you don't have to read everything. In my opinion it is better to put too much information in now and find ways to make it usable later than to not collect any info at all.

07/07/2008 20:15 #44897

Three Cheers to E:boxerboi
Category: heroes
My current inspirational summer hero is (e:boxerboi). He is taking on the formidable MUSSELMAN TRIATHLON CHALLENGE!!! this weekend!

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You could walk by his office and not notice the absolutely cool bloke who works there. But beneath his calm and almost zen-like efficiency lies the makings of a genuine hero! While lesser souls on the third floor show varying degrees of wimpiness and run around in circles, (e:boxerboi) quietly comes by and conquers the world! Like a true hero, he has a magically unceasing and very much hidden stash of some very lethal weapons.

1. Chuckles
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2. Blueberries
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Don't underestimate the power of these weapons of choice. They are jam-packed with massive undercurrents of overwhelming charm. Needless to say, I have been totally swept away and I hereby appoint him the

Hero of the Extreme 3rd Realm of Planet K
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Join me in wishing him all the very best of luck in his mission to conquer the Musselman World not once, not twice but a WHOLE THREE TIMES!!

THREE CHEERS to you, (e:boxerboi)!!! You ROCK!!!

07/04/2008 12:05 #44858

Subway. Finger-licking Freedom.
Category: eating out
I know I am mixing up punch lines and writing a blasphemously laudatory post about a fast-food place, but Subway deserves my respect in so many ways! I am not being paid an obscene amount of money for an ad campaign or miraculously losing bucketloads of adipose tissue by eating here but this chain has rescued me from many a day of hypoglycemia and certainly prevented me from turning cannibalistic. In due recognition of its consistent and gastronomically positive contributions to my life, I am going to do a (e:Drew)-style 10 things I like about Subway here:

1. It's the most healthful food you could eat if you are without access to your kitchen or in a tearing hurry or just poor.

2. If you wisely pick your sandwich (and yes, I do mean the veggie sandwich. I don't care what all you carnivores out there think. The veggie sub rocks your socks off!) you get a very balanced meal.

3. They have a superlative item on their menu that I can easily zone in on (the creatively but wrongly spelled Veggie Delite Sandwich, what else??!!). This eliminates my aimless-vacillation-time (AVT). AVT is the eternity that I spend making food decisions while people's heads around me explode with pent-up frustration at my indecision.

4. You get UNLIMITED veggies for a fraction of the money that you might spend for a similarly loaded meal elsewhere in the whole city. I regularly test out if the "unlimited" part of the veggie deal is true and almost invariably the place passes my exacting standards of veggie greed with flying colours. The Chippewa Subway also has BABY SPINACH! 'Nuff said.

5. The bread choices are delicious. And most of them are super healthful. The honey-oat bread is a gustatory dream with its chewy delicious texture and is an awesome boost to your daily fibre intake.

6. If you say the magic (and secret no more) word "double toast", you can get your bread of choice toasted *twice* to a glorious rich golden brown delicious scrunchy heavenly colour. I am running out of elaborate adjectives to describe how perfect the double toasted bread is. Everything tastes about a million times better with a double toast!

7. You could get cheese on your sandwich and not only benefit from all the amazing proteins and calcium, but also make your sub 10x tastier.

8. The wait time between your order and the first morsel reaching your mouth is ridiculously low. Since you can watch your sub being built, it's even shorter and livelier. It's almost sandwich-making-by-proxy; calming and fun! You don't have to sit at a table and wonder whether the kitchen ran out of tomatoes and are as a result raising them from the ground or direct a contemplative and lifeless stare at at your companion's hand with the eminent possibility of chewing it off in a demented fit of hunger.

8. The sub arrives and it's time to pay the bill. The price is so reasonable that it blows your mind. After aeons of being overcharged at every single place that is half as comparable to the Subway, you cannot believe that the fabulous piece of divine contentment you hold in your hands only costs $2.49 for a six incher and $5 for a footlong! If you have foupons, the cost is cut by a further $0.50 to $1.

9. There is no presumption or discrimination at a subway. It's the only place you feel equally at ease chatting up the stressed businessman who has dropped by for a quick bite or the bag-lady from the greyhound station who wants to stretch her last dollar for a substantial lunch. The subway is an oasis of socialism even within a capitalistic framework.

10. You could ask that your sub be loaded up with a truckload of Jalapenos and not have the person serving you give you the look of death or a disgusted stare.

On July 04, 2008, to me, the subway chain represents one of the many facets of freedom that this country lavishes on its residents - citizens or not.
heidi - 07/05/08 19:45
12" veggie delight on italian herb & cheese bread, some of each cheese including the shredded (depends on the sub-maker if I get charged for double cheese), toasted, chipotle sauce, baby spinach ("a little more spinach, please?"), cukes, tomatoes, green peppers, pickles, carrots (at the Mansfield subway, not available at the Walmonster franchise), oregano and shaker cheese. "That's the greenest sub I've ever made," said one sub-maker.

12" means I've got food for later.



metalpeter - 07/04/08 13:14
I'm not sure when the 1st time I ate there was but it was guessing before when Paul said but maybe around then. I myself like there meat but now with their new roast beef have to look to see if it is pink or brown some people like it pink but I don't (insert you're own pink joke here______________________________________________ ) . I like that you can see if everything looks fresh. and they do have pizza also and that isn't bad, my favorite is Buffalo Chicken or even to add Bacon to it. That brings me to my point that everyone thinks subway is healthy and Mcdonald's causes Heart Attacks. That isn't true it is about what you eat. For example once Bacon, Mayo or Cheese gets added or you go for double steak then the health drops. Just like you can go to Mickie D's and get salads like one guy did a drop hundreds of pounds. Since subway did there $5 promo I have gone a lot more. Taste is a very personal thing and so some people might prefer Quiznos but try finding one of those in Buffalo.
paul - 07/04/08 12:17
You should be paid for this, lol. No seriously, when I was younger I loved subway. Escpecially, once they had all those yummy brea choices.

When (e:terry) and I worked at HSBC downtown back in the early 2000s during our "lunch" break there were only two choices. Subway and McGuidos - an irish and italian place. That was really the name. The place has since closed down.

Anyways, we most often ate Subway and I actually got sick of it even thought I loved it. Also their meat is a little weird and over processed - you probably don't experience that.

07/03/2008 01:20 #44844

Yesterday
Category: art
I had a splendid time at the concert yesterday and I am more than convinced that sighting 5 (e:peeps) in one day is the secret recipe to that day's quota of perfect happiness. If the (e:peep) sighting number (EPSN) shoots up to more than 5, the levels of euphoria increase exponentially. I often experience it after (e:) strip parties. I catch myself unconsciously grinning ear to ear for more than 24 hours at a stretch.

The weather was so perfect that the popular song by the Carpenters got stuck in my head. I had to listen to some angry flamenco rough and raw music to erase that ridiculous song. The first (e:peep) sighting was of course (e:imk2) at work. I thought it was weird that she was tip-toeing it into the printer/mail room. I actually checked to see if she was wearing new shoes and had a shoe-bite or something. I learned later that she had been risking her life and limb by going in there. Apparently, a huge wasp was hiding in that room somewhere and the chair of the department had been trying to swat it dead. I am super glad I didn't see it. Who knows what I might have done to (e:imk2) with my tendency to throw extreme drama freak-outs. I saw (e:boxerboi) on the way home and we had a very soul-purging talk about how high-school has an annoying tendency to persist sometimes. :)

I persuaded a couple of my friends to walk to the concert but I omitted to tell them that it was a good half an hour's brisk walk from downtown to Bidwell. We were somewhat dehydrated by the time we reached the concert venue and dashed into Cafe Aroma to get something to drink. A bloke dressed as a huge Target dog entered and in a proper touristy fashion, we got all excited about being clicked with **the target dog**. However, before we could shoot, the target dog made a beeline for the bathroom and was decapitated by his target-mates. It was probably the most disappointing moment of the evening.

We ran into (e:James) at the Bidwell crossing. I was all worked up about missing the photo-op of a lifetime with **the target dog** and all I could remember was (e:James) had been recently promoted to a power position as a deputy commander of something political. That title stuck and I had to struggle not to introduce him as "The deputy commander!". A second title of "James, the terrible (multi-translation poet)!" suggested itself, but I choked that one down as well. Instead, I introduced him to my friends as a "very powerful politician". I could see (e:James) through my peripheral vision looking at me as if I were from planet loony but it was too late! I admit that it was a desperate and poverty-stricken moment for my brain and those are the times I say the weirdest things. So, you all better tell me in advance what you would like to be introduced as! Your profession choices range from God of the Mountains to Ruler of the Land of the Dead. Take your pick.

We finally made it to the frontlines and plonked down on the grass. The Buffalo Philharmonic played some very popular tunes in full regalia.
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However, this charming young couple stole a huge chunk of BPO's limelight by waltzing away in abandon in front of the stage. Their dance became more elaborate with every song and my friend and I were half expecting them to break into some crazy whirls and rock and roll dancing...
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That didn't happen. At the intermission, I was somewhat bothered by the fact that I could probably never play this cello because it was taller than I was.
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A thousand kids invaded the space in front of the stage. The concert was triple the fun just because of these little dancers. :)
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However, some stuffed up people were bothered and the primary conductor tried to rein in their exhuberance for a couple songs.
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But thankfully, was not very successful. :)
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This pretty young artist from Williamsville High School played as part of a scholarship to the BPO. Her oboe solo was pitch perfect and wonderful. I think her whole family was in the audience to cheer her on. It was very sweet.
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They had a raffle for this HUGE (and somewhat scary looking) stuffed dog sponsored by Target. No one claimed it for a very long time after the announcement.
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I was sorely tempted to go up and lie my way into getting it. It might have made a fabulous chair and totally made up for the missed photo-op with **the target dog***. Much to my disgust, I found that I did have a sneaky little conscience that prompted me not to pull off the smooth con act.
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I don't know if kids were losing their balloons or someone was intentionally releasing them every 15 minutes or so. They were so cool to watch in the cloud streaked sky.
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The band struck up the chords of the most covered and yet the most perfect song ever recorded in the history of pop - Yesterday. Here's a choir version to give you an idea of how heavenly it sounded.

::DOWNLOAD SOUND::



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The sunset was gorgeous.

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On our way back, just as I was telling my friends that it would be so cool if they got to meet (e:drew) and (e:janelle), I walked almost right into (e:drew)! He and (e:Jason) were folding up the chairs. We walked halfway home with them. Enroute, I heard about the heroic story of Roberto Clemente Walker I was told that my lurid suspicion that his plane might have been sabotaged was not really true. Oh well. I guess real life imitates inspiring tragedies rather than spiffy spy movies. The excellent alliterative phrase "mediocre medium" was mentioned in relation to a video game called "Guitar Hero" - I think by (e:Drew).

After (e:Drew) and (e:Jason) turned into Lexington, we ran into none other than (e:fellyconnelly) and the king of (e:) strip, (e:RRRAAALLPPPHII)E! The excitement of finally seeing Ralphie was a like a shot of a crazy drug and my already fried brain could not recall (e:fellyconnelly)'s real name. If you thought (e:James) got a raw deal, hear this. I introduced her as Raphael. Raphael! Holy crackers, I couldn't even think of a modern name. I had to pick something from the 1600s. Don't ask me why!

All of (e:fellyconnelly)'s recent blogging was enacted in real life. My friend and I went down on our knees and cooed all over the little guy. (e:fellyconnelly) rules Ralphie's world. She held out some magic potion and Ralphie stood still for a photograph!
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Special thanks to my friends who tolerated my non-stop brainless jabbering and came out with me to enjoy the evening and to all the (e:peeps) who made it even better! It was an awesome official grade 5-EPSN yesterday. :)

metalpeter - 07/04/08 11:26
It sounds like you had a really good time and it is a pretty post also.
james - 07/03/08 21:45
I didn't mean to look at you like you were crazy. I was a little rushed to get a project started and my cohorts were ready to desert me. Feel free to introduce me in the future of "Ruler of the Land of the Dead." It is a very nice title.

And you can still play cello. That was a bass on its side. So cello it up Pliny and we can start a rock band!
drew - 07/03/08 11:18
Just for the record, I am a "mediocre hard," and an "excellent medium" guitar hero.
paul - 07/03/08 09:50
Congratulations - this is your 100th journal.
mrmike - 07/03/08 07:36
Sounds and looks like a thoroughly awesome day :)