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Below is a complete set of lyrics and credits for the album My Dissertation. All songs were arranged and produced by Do Peterson.
1. Performance
words by Do Peterson and Jessi Roemer; music by Do Peterson
Do: Lead Vocal, Guitar and Drum Machine
No Relationships to Disclose.
My advisor and me hide nothing below.
No deals were made or profits taken.
So you can trust what I'm presenting.
Showing Performance
Solo Performance
Done a lot of work to get this far.
The knowledge I've gained has come so hard.
Six long years of sweat and heart,
I take this work and create art.
Showing Performance
Solo Performance
Performance, Perform
2. Title Slide
written by Do Peterson
Do: All Vocals, Guitar, Synth, Drum Machine and Jaw Harp
Kirk L. Van Scoyoc: Banjo
Henry Burt: Guitar, Chaplain to the Banjo Player
The title of my talk is
"Distribution theory
For the sibling recurrence risk ratio."
My name is Do Peterson.
I hope you understand me
While I explain the recurrence risk ratio.
At Biostat Department,
I receive my training
At the University of Washington.
From Professor McKnight,
I get my advising
At the University of Washington.
At some point in my talk,
I hope you understand me
While I explain the recurrence risk ratio.
The title of my talk is
"Distribution theory
For the sibling recurrence risk ratio."
(etc...)
3. ASP (Affected Sibling-Pairs)
written by Do Peterson
Do: All Vocals, Acoustic and Electric Guitars, Bass, Synth and Drum Machine
Oh affected sibling pairs
Groove the background motivation
Oh affected sibling pairs
Pump the context cogitation
Oh affected sibling pairs
Pump the mental preparation
Oh affected sibling pairs
Groove the background motivation
Oh...
The distribution theory
That I mentioned in my title slide
Is direct'ly applied
To what is called linkage analysis.
The linkage analysis data
To which this distribution theory will be applied
Will come from affected sibling pairs now
Two girls, two boys or a girl and a guy.
Oh affected sibling pairs
Pairs of siblings, both affected
Oh affected sibling pairs
Pairs diseased that we've selected
Oh...
Now the kind of data
Collected from the siblings pairs
Is called genetic marker data,
Is in the form of counts of marker alleles.
Now the marker data
Identical by descent, you see.
The acronym is IBD
which means the same ancestral marker copy.
Oh affected sibling pairs
How many markers do you share
Oh affected sibling pairs
Get our marker data there
Oh affected sibling pairs
Pairs of siblings, both affected
Oh affected sibling pairs
Pairs diseased that we've selected
Oh...
Linkage analysis,
You find the place of disease genes.
The chromosome location
Or locus is what we glean.
It can be shown that markers
Shared by affected sibling pairs
More often than expected is evidence
Disease gene is near.
How much more often than expected is an amount
That can be tested.
We're figuring out whether or not
Our method cannot be bested.
Oh affected sibling pairs
Pairs of siblings, both affected
Oh affected sibling pairs
Pairs diseased that we've selected
Oh...
Oh affected sibling pairs
4. R3 (Recurrence-Risk Ratio)
written by Do Peterson
Do: Lead and Background Vocals, Electric Guitars, Groove Box, Drum Machine, Synth
Tanya Shaffer: Background Vocals
I'm introducing here λS,
Widely used for linkage analysis,
Often used in genetic epi studies.
This our parameter of interest,
A ratio that I'll use for my test,
A ratio comparing situations.
If this risk ratio is greater than one
Is evidence disease is family sprung,
Is evidence disease is aggregated
In families; we use the sibling pairs
To try to find relationship is there
Significantly within family structure.
Chorus:
The probability that you are affected
Given your sib'ling is also affected
Compared to population prevalence
Of the disease.
Please, let me introduce the
Recurrence-risk ratio...
...for siblings
...Risch 1990
...AJHG
...Articles I, II and III.
Marker data from affected sibling pairs
Make up an estimate risk ratio, where
We test a null of no genetic linkage.
When we reject the null hypothesis,
λS greater than 1 shows us
Some evidence disease and marker locus linked.
(Chorus)
5. Single-lo
written by Do Peterson
Do: Triangle, Sampler, Background Vocals, Drum Machine, Synth
Spoken Vocals (in order of appearance): Karen Stensrude, Lori DeGloria, Henry Burt, Leonard Wainstein, Natalia, Danstan Bagenda, Tien Thach, Jessi Roemer, Greg Crowther, Clarence Lewis III, Lori D., Anne-Louise Leutenegger, Christopher Pesce, Stephen Espinola, Erin Kamler, Kirk L. Van Scoyoc and Do
The linkage test we are developing is a single-locus method.
It assumes one disease gene is responsible for the disease.
It uses a genetic marker at a single locus.
We are using data at one marker locus to find this disease gene.
Single-locus methods are quick and easy to use.
You can publish your results right away.
They do not require marker data from extended families which are often difficult to find.
The false positive rate or level of the test is the same regardless of the penetrance structure of the disease gene.
Penetrance structure as in dominant or recessive penetrance.
The power of the test depends on this penetrance structure.
Our method uses this information on single-locus models to create powerful tests.
6. Outline
written by Do Peterson
Do: Lead Vocals, Doobies, Guitars, Groove Box, Synth
Lori DeGloria: Doobies
doobie doobie dip dow
doobie doobie dip dow
doobie doobie dip dow doobie
I just gave the motivation
And the background.
Next I'll show
The linkage test and example
Just how it works,
Listen, look.
Here is the outline.
Here is the outline...
...I've organized
...To scrutinize
...To synthesize
Background and Motivation
Genetic Linkage Test, Oh...
Example Exposition
And Further Interests, Oh...
Here is the outline.
I just gave the outline
Of my lecture
Next I'll show
The linkage test and example
Just how it works,
Listen, look.
7. What Are the Assumptions?
written by Do Peterson
Do: Lead Vocal, Electric and Acoustic Guitars, Bass, Drum Machine
Jessi Roemer: Backup Vocal, Acoustic Guitar
Steve Espinola: Piano
Christopher Pesce: Bass
Doug Lauen: Backup Vocal
Lori DeGloria: Backup Vocal
What are the assumptions?
written by Do Peterson
We assume
Single putative disease locus,
One disease gene at one place.
We assume
Marker locus, disease locus
Completely linked, moving together.
We assume
Normal fitness of reproduction
In affected individuals.
We assume
Ascertainment from the population
Of affected sibling pairs at random,
Pairs at random.
What are the assumptions?
We assume
Markers highly polymorphic
Polymorphic markers: What does it mean?
What does it mean?
Genetic marker and it really polymorphic
Highly polymorphic, Yeah,
What does it mean?
It mean that chances are,
Are really heavily in favor:
One locus, two parents, four different alleles...
...once again
...everybody
Four different alleles.
I got a marker and it polymorphio!
My marker and it polymorphism.
Disease gene and it polymorphism.
Gene and marker and they polymorphism.
I got a marker and it polymorphio!
Marker locus on the same chromosome as the
Disease locus on the same chromosome; so we have
Two loci on the same chromosome,
And they got linkage.
These are the assumptions.
8. Marker Data
written by Do Peterson
Do: All Vocals, Synth, Groove Box, Sampler, Drum Machine
Marker data, data, ...
We have three numbers here:
X0, X1, X2
i = 0, 1 or 2
Xi the count of sibling pairs
Affected sibling pairs
That share i number of alleles
Identical by,
Identical by descent
Additive, Multiplicative
Penetrance Structure
Recessive, Dominant
Penetrance Structure
Marker data
9. Likelihood, Oo!
written by Do Peterson
Do: All Vocals, Guitar, Synth, Drum Programming
Likelihood, oo... Likelihood ratio test, oo...
I got a delicious little likelihood to share.
I got a delicious little likelihood to compare
The MLE on top
With the null parameter value
On the bottom.
When we are comparing the data to
What we assume is true,
I got a likelihood ratio test
Make it easy for you,
If you want to compare
The MLE on top
With the null on the bottom.
The MLE
The Maximum Likelihood Estimate
Yeah, it's cool.
The MLE
Is a function of our fine data
Is a likelihood ratio flava
Our convenience is so much greater with
Likelihood, oo... Likelihood ratio test, oo...
The null will be
Hypothesized, no linkage,
What we assume.
The null will be
Sib Risch ratio value equal
Unity, so easy.
And when our likelihood ratio test is done,
There is plenty of time to go out and have fun.
Because it just doesn't take much time
To use our
Likelihood, oo... Likelihood ratio test, oo...
Bop!
10. Under the Null (Under Additive, Multiplicative and Recessive Penetrance)
written by Do Peterson
Do: All Vocals, Electric and Acoustic Guitars, Bass, Drum Machine, Synth
Note: LRT = Likelihood Ratio Test
Part 1: Under the additive, multiplicative and recessive penetrance
Part 2: Under the null hypothesis (repeated), under the null,
Under the null hypothesis (repeated), no linkage. No.
Part 3: Event A, X2 greater than or equal to X0
Event B, X2 strictly less than X1
Event A, LRT chi-square one approximately
LRT, Event B, equals 0 exactly
Exactly...
What we have found
What we have found...
...Event A, Event B
...have the same probability
...and this implies the following
...mixture distribution for our LRT
Research was slow -- dominant penetrance.
We almost know. When we do we'll publish.
What we have found...
...one half chi-square with one degree
...plus one half zero asymptotically
...this mixture that you see
...a mixture distribution for our LRT
We still don't know -- dominant penetrance.
We still can't show its distribution theory.
Under the null hypothesis, no linkage. No.
No linkage; no.
What we have found.
11. An Example Show
written by Do Peterson
Do: Lead Vocal, Guitars, Bass, Synth, Drum Machine, Shakers
Lori DeGloria: Background Vocals
Spoken Vocals (in order of appearance): Tanya Shaffer, Julianna Haubrich, Chaya Moskowitz, Miky Ishida
"Yeah" Group: Anne-Louise Leutenegger, Kathy Thomas, Jani Drabek, Heather St. John, Matt Garvert, Laura Castleberry, Tomislov Maric
In this example, we have 100 affected sibling pairs
Mr. Peterson, what exactly do you mean?
What this means for recessive and multi....
Could you repeat that?
What this means for recessive and multiplicative penetrances...
I don't get it.
Mr. Peterson...Mr. Peterson....
Welcome the mailman. Hi five the cashier.
Smile at the dentist. There is no shame here.
Is an example show. Is an example show!
Just look at the slide, is an example show.
Right there before your eyes
Is an example show.
100 sibling pairs divided not by chance.
P-values indicate we have significance.
Verse 1:
Hug your neighbor. Kiss the baby.
Help the old man. Charm the lady.
Dance calypso. Do the cha cha.
Make it spicy like the salsa.
Let your feelings go. Is an example show.
Let the good times roll at the example show!
Just look at the slide, is an example show.
Right there before your eyes
Is an example show.
The numbers shown right there
Were conjured up by me.
We have significance for both our MLE's.
Verse 2:
Send some candy to your mother.
Dress up fancy. Call your lover.
Clap your hands and show your beauty.
Move your hips and shake your booty.
Is an example show. Loosen up your clothes.
It's time to tap your toes at the example show!
Now!
Performance, Performance...
In this example, we have 100 affected sibling pairs: 15 that share 0 alleles identical by descent, 48 that share 1 and 37 that share 2 alleles identical by descent. What this means for recessive and multiplicative penetrances is that the maximum likelihood estimate of our sibling recurrence risk ratio derived from the data is significantly, highly significantly greater than 1. A similar result can be seen for the additive penetrance.
La la la la la ...
...is an example show
...we have significance
...let's do a happy dance
Mr. Peterson, what exactly do you mean?
Move your hips and shake your booty. Yeah!
Clap your hands and show your beauty. Yeah!
Dress up fancy. Kiss your lover.
Send some candy to your mother.
(Verse 1)
Is the example show, food to lift your soul.
At the example show, it is magnifico!
12. Sense and Context
written by Do Peterson
Do: All Vocals, Triangle.
The title as you may remember is Distribution Theory for the Sibling Recurrence-Risk Ratio.
Now I hope this title makes sense and has context.
Let us think about what we have heard.
Please feel free to ask a question after I list a few of my ideas and interests for further work.
Please join in silent meditation.
13. Discussion Percussion
written by Do Peterson
Do: All Vocals, Guitar, Synth, Drum Programming, Whistling
Kirk L. Van Scoyoc: Banjo
And for my final slide, here are some areas of further work.
Chorus:
On two disease locus modeling,
The structures of larger pedigrees
And issues of ascertainment schemes,
When incomplete linkage is addressed
In power of likelihood ratio test,
When there are less marker types than ideal,
Will this method still appeal?
Discussion, Percussion
Back and forth banter of my creation
The synthesis and context of my frustration
Gonna be:
The further work you're gonna see,
The questions that you have for me,
I try to respond with clarity,
As I perspire conspicuously.
(Chorus)
Discussion, Instruction
Listing of interest in further working
While bracing myself for comments lurking
Gonna be:
Exposing the holes I didn't see,
Remarking upon the cogency
Of points I made a priority,
Commenting with frank brutality
And picking apart infinitessimally
My presentation, this information,
This Dissertation.
I'll take comments and questions now. Thank you very much.
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