Gpuccio: Functional Information Methodology

[swamidass (S. Joshua Swamidass)]

@Gpuccio, it is great to see a starting point of a response from you. We aim to key the conversation substantive and professional. It doesn’t always go that way perfectly, but that is our goal. I hope that we would all understand each other, and science, better through exchanges like this.

A few thoughts to offer as we await a longer response from you.

Interesting Hypothesis

@gpuccio

The hypothesis he is testing is interesting

Thank you! Seriously, this is one of the biggest acknowledgments I have ever received from the other side.

It is an interesting hypothesis, and it deserves to be received with seriousness and rigor. Good ideas come from all over. The beauty of how science works is that we can, if we are humble to the data, come to common understanding through engaging hypotheses like this. Even failed hypotheses have value for this reason.

Whether or not this hypothesis pans out, our success/failure is determined by the rigor with which we test the hypothesis, and our ability to come agreement (especially across camps) over evidential claims concerning the hypothesis.

Terminology Flubs are Human!

@gpuccio

However, I can see that in a later comment John_Harshman comes to my (partial) rescue, stating:

“As for the confusion of homology with similarity, that seems common among molecular biologists, not just Gpuccio.”

Thank you. Being human, I can find some small consolation in not being alone in my errors!

@gpuccio

Obviously this is not among the most important critiques, but Gpuccio seems to not understand what homology means. It’s a binary state. Two sequences (or characters) are either homologous or they are not. It’s nonsensical to assess the “degree” (e.g., high or low) of homology. I presume he means sequence identity, which is really not at all the same thing.

Well, thank you for the correction. I am a medical doctor, and not a biologist, so some imprecision in terminology on my part can be reasonably expected. I will be happy to acknowledge any well explained correction.

As far as I am concerned this is a non issue now. Many biologists make this mistake, and you are adjusting. Thanks for hearing @davecarlson and @John_Harshman out. It is a fairly common mistake, even among biologists, and it does not affect the substance of your argument.

The Central Methodological Issue

It seems that central methodological issue is:

@John_Harshman

A few thoughts. First, it seems to me that a simple pairwise comparison is completely inadequate for what he claims to be doing, and using the actual phylogenetic tree, with lots of chordate sequences, would better enable him to do what he seems to be trying to do here very clumsily, which is to estimate the sequences at internal nodes. And also to estimate sequence conservation. More work than clicking on a few buttons in BLAST, but a much better approach. Oh, I see @davecarlson has already mentioned this.

As I explained, there is a mapping between bitscores and the phylogenetic analysis. I hope my explanation made sense. It seems like it would be far more methodologically grounded to move into the phylogenomic analysis, and translate back to BLAST if you want to compare results.

How familiar are you with BLAST bitscores? Do you know how they are generated? Do you understand the assumptions involved in how they are computed? The gap between reality and these assumptions, I believe, undermines your case. If you switch to a better methodology, this objection would go away, and you would still be able to cross check with your prior results.

Interpreting What We Expect

This paper recently posted by @sfmatheson has a figure that tells us what we expect to see with the new analysis.

https://www.cell.com/current-biology/fulltext/S0960-9822(15)00928-8

Here, branch length is going to be linearly correlated with “FI gain,” as you call it. If you look at vertebrates here, the length of the branch is not remarkably or unusually long. If your results look much like this, it seems that it would count against your analysis. If the data did end up like this, do you agree it would count against your hypothesis?

Your Data is a Good Starting Point

@gpuccio

In brief, I have tested the whole human reference proteome against 9 groups of organisms, chosen, with some practical compromise, to represent the natural history of metazoan. For each human protein, a blast comparison was made versus all the protein sequences present in the NCBI database for that group of organisms, and the best hit chosen. I used the donwnaded version of Blast to perform the comparisons automatically.

So, my database has the best hit of each human protein with each class of organisms, in terms of bitscore, bits per aminoacid, and difference with the previous class. I use that database for all my analyses, and the R software to analyze results and draw graphics.

I really love that you are looking at the data yourself. You clearly have the ability to run much of these anlayses yourself. Great!

Let’s talk about how to analysis with phylogenies. I recommend following @Jordan’s contributions to this thread: John Harshman: The Phylogeny of Crocodiles. There are several programs you can freely download to use on your sequence database. It would be really interesting to look at your results in comparison to the tree I just posted.

Next, it seems your analysis would benefit immensely by augmenting it with more organisms, at least one from each of the terminal clades in the tree I posted above. It would be valuable, again, to see how your results compares with that tree. It would be interesting to see how including more genomes affects your conclusions. It would be interesting to see what sorts of deviations from the consensus tree you can find.

Some Parallel Questions

From hearing about your work from others, and reading your articles, I wanted to clarify your position. It sounds like you:

1. Believe in an old earth.
2. Affirm common descent of humans with the great apes.
3. Are arguing that there is evidence for design in the origin of phyla.
4. You conceive design as information infused into the common descent process.

Is this about right?

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I’m looking forward to seeing the conversation continue.