# Winston Ewert: The Dependency Graph of Life

**URL:** <https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728>\
**Category:** Office Hours\
**Tags:** Design\
**Created:** [July 21, 2018, 2:51am UTC](https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728 "2018-07-21T02:51:30Z")\
**Posts on this page:** 6\
**Page:** 2

<div class="post-metadata">

**Author:** ![Winston\_Ewert](https://avatars.discourse-cdn.com/v4/letter/w/9dc877/32.png) [@Winston\_Ewert](https://discourse.peacefulscience.org/u/Winston_Ewert)\
**Post date:** [July 21, 2018, 9:42pm UTC](https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728/30 "2018-07-21T21:42:37Z")

</div>

> [@swamidass](#):
>
> In service of this goal @Winston_Ewert, **can you make available to us the results you computed for this study**? In particular, I want like to see the full dependency graph you compute, in all its gory detail. I’m sure you have them in text files somewhere. I’d like a copy of it, with a reasonable README file.

I thought people might like to see it, which is why its available in the supplemental data from the bio-complexity website.

> [@sygarte](#):
>
> I find the very large differences in data fitting probability given in Table 4 surprising, and I was wondering if other methods would show similar large differences between the two models.

Josh has said pretty much exactly what I would have said.

> [@swamidass](#):
>
> I think a better question concerns the fit we would get from an _undirected graph model_ versus a dependency graph (which is a directed graph), using the **same** penalization.

Yes, that is an important question that will need to be addressed.

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [July 21, 2018, 9:44pm UTC](https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728/31 "2018-07-21T21:44:03Z")

</div>

> [@Winston\_Ewert](#):
>
> Firstly, I see that I need to clarify the nature of the argument I made in the paper.

Okay, great.

> [@Winston\_Ewert](#):
>
> If my hypothesis is correct, this predicts that a dependency graph ought to be a better fit to the biological data than a tree. This prediction is fulfilled, thus providing some level of evidence that my hypothesis was correct.

I hope that isn’t your argument. We already know this to be true from other literature, for other reasons. The only reason we would think common descent would not produce violations of a tree is if we were using a strawman version of common descent (not saying you are doing that here).

The real question, it seems, is different. You have to show that this model works better than the current best models of common descent, which right now are undirected graphs. Even then, I can give an account of why you might get a signal (and it would be exciting if you did).

> [@Winston\_Ewert](#):
>
> Such an argument would not be valid. Instead, I’m merely arguing that this fulfills a prediction.

I can grant you that, but that is a meaningless claim. That is not how we adjudicate models in computational biology.

> [@Winston\_Ewert](#):
>
> The challenge this leaves to common descent is explaining why this prediction worked.

Why exactly? I can produce strong evidence that human diversity does not follow a tree, even though we all agree it arises from a process of common descent. That is de facto evidence that common descent does not produce DNA that fits a tree perfectly.

> [@Winston\_Ewert](#):
>
> As for 2, I do have deletions in my model. But I’m curious about how you see large scale genome rearrangement playing into this. Since I’m just looking at the presence or absence of gene families, I’d think a rearrangement wouldn’t do anything interesting there. But presumably you know something about that which I don’t.

> [@Winston\_Ewert](#):
>
> What I’m surprised by is you not bringing up horizontal gene transfer. Do you not think it is a good candidate?

I do think horizontal gene transfer is important, but I’m not sure that is the dominant process involved here.

Large scale genomic rearrangements can create correlated deletions in multiple branches of the tree. One test for this is to see if modules are correlated with synteny. I expect they are. If so, that gives a fairly straightforward reason for why the data shakes out this way.

> [@Winston\_Ewert](#):
>
> As for 3, it seems to me that this should be taken care of by the probabilistic analysis.

Not necessarily. It gets into the details of how you handle pseudogenes (or what ever you want to call what looks like inactivated genes). In a proper analysis, you’d have to call each _type_ of inactivation a different _type_ of gene family, whether or not they actually are functional. That, it seems, will really break your analysis. Though you are welcome to prove me wrong.

> [@Winston\_Ewert](#):
>
> My thinking is that none of these mechanisms seem like good candidates to explain my successful prediction.

As I’ve said, the human diversity data is _de facto_ evidence that your intuition is wrong. I haven’t posted papers on this yet, but I will when you are ready to take a look.

> [@Winston\_Ewert](#):
>
> So, yes, dealing with the exact sequence (instead of just gene family) and in particular the more neutral elements of that sequence is really key. If that can’t be done my proposal fails. It remains to be seen whether a model can be developed here.

Once again, that is honesty. You are earning trust every time you do that.

> [@Winston\_Ewert](#):
>
> It should be emphasized, the fact that human variability deviates from the expectations of tree does not automatically mean that it will fit a dependency graph better. So its very much an open question as to what the results will look like.

True. We do, however, know that an undirected graph does better than a tree. The finding that a middle ground model (a directed graph) fits better than a tree is no surprise. That is what everyone should have predicted. The real question is if your middle ground model does better than the state of the art, which is NOT a tree.

**Back to you all. I’ll respond more later.**

---

<div class="post-metadata">

**Author:** ![Winston\_Ewert](https://avatars.discourse-cdn.com/v4/letter/w/9dc877/32.png) [@Winston\_Ewert](https://discourse.peacefulscience.org/u/Winston_Ewert)\
**Post date:** [July 21, 2018, 10:11pm UTC](https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728/32 "2018-07-21T22:11:36Z")

</div>

It seems to me that this conversation has served its purpose.

I’ve acknowledged the limitations of what I’ve done so far. You’ve pointed out the limitations and the sorts of issues that need to be dealt with. They largely correspond to what I’d already thought would be the concerns with a few surprises. Now I need to go ponder these things for a while.

Thanks everyone

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [July 22, 2018, 1:18am UTC](https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728/33 "2018-07-22T01:18:00Z")

</div>

A post was merged into an existing topic: [Side Comments on The Dependency Graph of Life](https://discourse.peacefulscience.org/t/side-comments-on-the-dependency-graph-of-life/743/7)

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [July 22, 2018, 1:50am UTC](https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728/34 "2018-07-22T01:50:19Z")

</div>

> [@Winston\_Ewert](#):
>
> I’ve acknowledged the limitations of what I’ve done so far. You’ve pointed out the limitations and the sorts of issues that need to be dealt with. They largely correspond to what I’d already thought would be the concerns with a few surprises. Now I need to go ponder these things for a while.

I agree.

> [@swamidass](#):
>
> The real question, it seems, is different. You have to show that this model works better than the current best models of common descent, which right now are undirected graphs.

> [@swamidass](#):
>
> Why exactly? I can produce strong evidence that human diversity does not follow a tree, even though we all agree it arises from a process of common descent. That is de facto evidence that common descent does not produce DNA that fits a tree perfectly.

Just to help you out, here is on example of a study that shows human diversity (which obviously results from common descent) does not show a tree pattern ([https://doi.org/10.1534/genetics.115.182626](https://doi.org/10.1534/genetics.115.182626)). I can produce more examples when you are ready to engage on that. Alan Templeton, a leading population geneticist, argues that not a single human diversity dataset he has examined survives a statistical test to see if it is a tree (private communication).

As I stated earlier, human variation data serves as an excellent negative control. If you solve the technical problems in this approach, the signal should disappear when you look at human diversity data. Gnomad ([http://gnomad.broadinstitute.org/](http://gnomad.broadinstitute.org/)) should provide more than enough data to test this. When that analysis is done, whatever the results, please let us know. Even if it does not work out, you get credit for being upfront about the negative results.

> [@Winston\_Ewert](#):
>
> Thanks everyone

Thank you too. It has been a pleasure having you here. Whenever you would like to re-open the conversation, let us know. I will reopen it for you. It seems like many of us are looking forward to seeing how this develops.

* * *

**Cite this exchange with DOI: [10.5281/zenodo.1318762](https://doi.org/10.5281/zenodo.1318762).**

## This thread is closed but the side conversation continues. Join us here with your questions: [https://discourse.peacefulscience.org/t/side-comments-on-the-dependency-graph-of-life/743](https://discourse.peacefulscience.org/t/side-comments-on-the-dependency-graph-of-life/743).

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [July 22, 2018, 1:50am UTC](https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728/35 "2018-07-22T01:50:26Z")

</div>



[Previous page](https://discourse.peacefulscience.org/t/winston-ewert-the-dependency-graph-of-life/728.md?page=1)