[GET-Editors] Editing questions

Madeleine Price Ball meprice at gmail.com
Wed Oct 13 15:20:27 EDT 2010

On Wed, Oct 13, 2010 at 3:04 PM, Kimberly Robasky <krobasky at gmail.com> wrote:
> With regard to the following variant as an example:
> http://evidence.personalgenomes.org/SLC45A2-E272K: This is a pigmentation
> allele, so I set severity & treatability to 0.  Is that why this is still
> considered to be insufficiently evaluated?

Currently the scores are:
Computational: -
Functional: 5
Case/Control: -
Familial: -
Severity: 0
Treatability: 0

Because this is classified as "benign" you're right, the severity and
treatability should be zero -- we actually intend to gray this out and
not give any option of scoring here. It's kind of silly to even give
the option.

Notice there's a difference between filled-in "0" and unevaluated "-"
-- the first means someone has looked and concluded there is no
evidence for that category. The dashes here are what is making this
insufficiently evaluated, because you haven't declared that you looked
for and failed to find evidence in those categories. The stars are
grayed out on the website to represent this.

Currently "sufficiently evaluated" requires:
* 1 of case/control or familial evaluated (missing here)
* 1 of severity or treatability evaluated (should be irrelevant for
benign variants)
* at least 4 of 6 total evaluated (only 3 here, should be reduced to
not count severity/treatability for benign variants...)

Regarding the evaluation itself -- I don't see that you've mentioned
any evidence justifying any stars in functional (it looks like it
should go into case/control), hopefully answers to the following

> On the same example, how do I calculate the case/controls 'significance'?

We've been using a two-tailed Fisher's Exact test. You can find some
calculators online, for example:
Each box in this is case+, case-, control+, control-, accourding to
your data (28, 338, 50, 2320) this is < 0.0001.

To get odds ratio (OR): (28 / 338) / (50 / 2320) = 3.84

That puts SLC45A2-E272K at four stars based on the data from Graf et
al you recorded, according to the current criteria.

>  How do I calculate familial LOD score?

This is complicated -- first you'll need a pedigree. I mean to write
up a guide on it, although I'm still not totally confident that I
understand it correctly. Sometimes a paper mentions LOD, in which case
you can use that. If there aren't pedigrees (for example, everything
is case/control data) then familial evidence is zero stars.

 -- Madeleine

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