A Ubiquitin Response to Gpuccio

[colewd (Bill Cole)]

@swamidass

I did. My graduate student did. We falsified his conjecture.

Can you be more specific?

[swamidass (S. Joshua Swamidass)]

@colewd

I did. My graduate student did. We falsified his conjecture.

Can you be more specific?

How about this. Rather than arguing Durston’s case by proxy, invite him here. See how he does. If he won’t come, you have your answer.

[colewd (Bill Cole)]

@T_aquaticus

For a full test you would need to look at a random library of proteins that have a minimum of 400 amino acids each.

On what basis are you making this claim?

[T_aquaticus]

@colewd

On what basis are you making this claim?

I don’t know of a method that allows you to predict protein function for a random peptide library. There are methods that can make predictions if the sequence is similar to proteins of known function, but that method can’t tell you the function of a random protein.

If there is such a method I would like to know about it, as would the entire field of protein chemistry.

[colewd (Bill Cole)]

@T_aquaticus

I don’t know of a method that allows you to predict protein function for a random peptide library. There are methods that can make predictions if the sequence is similar to proteins of known function, but that method can’t tell you the function of a random protein.

If there is such a method I would like to know about it, as would the entire field of protein chemistry.

Do you understand Axe’s method and how he set up the experiment? Do you understand there is an alpha and beta chain to the enzyme he was testing?

[colewd (Bill Cole)]

@swamidass

How about this. Rather than arguing Durston’s case by proxy, invite him here. See how he does. If he won’t come, you have your answer.

I don’t know what to invite him to. I have had a few discussions with him at TSZ. All you have claimed is that you have falsified his claim without stating what the claim is and why you think his method is inadequate. It happens to be one of two methods I have seen for estimating FI. If you have a third that would be interesting to compare.

He is estimating substitutability of AA’s. Don’t you agree that goes a long way toward understanding FI if you can come up with a reasonable approximation?

[swamidass (S. Joshua Swamidass)]

@colewd

How about this. Rather than arguing Durston’s case by proxy, invite him here. See how he does. If he won’t come, you have your answer.

I don’t know what to invite him to. I have had a few discussions with him at TSZ. All you have claimed is that you have falsified his claim without stating what the claim is

Bill you are nice guy, but sometimes I wonder if we are in the same conversation or not.

@swamidass

@colewd. This equality is a conjecture by Durston that he never tests nor can he prove. The left part of the equation is meant to refer to FI, but the right side is FSC. He is conjecturing here that FSC = FI, but he does not demonstrate this true.

In fact we find the opposite, that FSC does not measure FI, as I explained about. Just stating a conjecture in mathematical form does not prove it true. It is still a conjecture till it is validated. Durston never even tries to validate it or to prove it. One my graduate students did and showed it is false. He is making an error very similar to @EricMH.

@swamidass

I disagree. I think this was part of his estimation of AA substitutability was all about.

He did not do any experiments. I know because I’ve asked him directly about this.

@swamidass

He is making an estimate of substitutability of AA based on sequence data. He is trying to estimate the total number of functional sequences which is the point I am trying to make with T. We will never be able to search all possible sequences as I know you realize.

He did not even do simulation experiments that were valid.

I did. My graduate student did. We falsified his conjecture.

@colewd

All you have claimed is that you have falsified his claim without stating what the claim is and why you think his method is inadequate.

I did state the claim I falsified. See quotes right here. If we can’t even keep track of this, what exactly is a reasonable expectation here?

As for Durston, invite him to explain his work to me here.

[colewd (Bill Cole)]

Josh
Lets agree to disagree here. This maybe my issue but I see no basis at this point to engage with Kurt.

[swamidass (S. Joshua Swamidass)]

@colewd

Josh
Lets agree to disagree here. This maybe my issue but I see no basis at this point to engage with Kurt.

We can always agree to disagree. You do not need to talk to Kurt. Honestly, at this point, I probably will when I have some time.

However, it should be clear:

1. He conjectured that FSC is a measure of FI
2. He has not provided evidence that FSC is a measure of FI, other than restating the conjecture with great confidence.

[colewd (Bill Cole)]

@swamidass

1. He conjectured that FSC is a measure of FI
2. He has not provided evidence that FSC is a measure of FI, other than restating the conjecture with great confidence.

I don’t doubt you are right on these points and will concede for arguments sake.

I am too new to FSC to competently debate its relation to FI. My real interest at this point is in his method measuring of FI and comparing and contrast to gpuccio’s or any other attempt at quantification.

[swamidass (S. Joshua Swamidass)]

@colewd

I am too new to FSC to competently debate its relation to FI. My real interest at this point is in his method measuring of FI and comparing and contrast to gpuccio’s or any other attempt at quantification.

They are failed methods of computing FI. In contrast, take a look at a successful method: Computing the Functional Information in Cancer.

[colewd (Bill Cole)]

@swamidass

They are failed methods of computing FI. In contrast, take a look at a successful method: Swamidass: Computing the Functional Information in Cancer.

What is the basis of your hypothesis that cancer is producing FI?

[swamidass (S. Joshua Swamidass)]

@colewd

They are failed methods of computing FI. In contrast, take a look at a successful method: Swamidass: Computing the Functional Information in Cancer.

What is the basis of your hypothesis that cancer is producing FI?

It has new functions. Everyone agrees with that, even ID leaders. They just claim the new functions arise in an easy to evolve way. We compute that this “easy” way to evolve is over 600 bits of FI. Cool right?

[colewd (Bill Cole)]

@swamidass

It has new functions. Everyone agrees with that, even ID leaders. They just claim the new functions arise in an easy to evolve way. We compute that this “easy” way to evolve is over 600 bits of FI. Cool right?

What new functions that don’t already exist in the cells?

[swamidass (S. Joshua Swamidass)]

@colewd

It has new functions. Everyone agrees with that, even ID leaders. They just claim the new functions arise in an easy to evolve way. We compute that this “easy” way to evolve is over 600 bits of FI. Cool right?

What new functions that don’t already exist in the cells?

Yup. That is right. New functions that do not already exist in the cells. I’ve pointed you to this link several times. Another one of those moments I wonder if we are in the same conversation. If you don’t ever engage, how can either of us make progress?

Good news too. Looks like @Kirk is here. Maybe he will join in. (Welcome @Kirk, nice to see you!)

[colewd (Bill Cole)]

@swamidass

I’ve pointed you to this link several times.

I know. I have been struggling to follow your argument. Let me follow along with you and Eric for a while. I am admittedly confused between all the definitions of information.

My studies of cancer have been observations of loss of cellular regulation and from my perspective loss of functional information as regulation systems like the ubiquitin system have parts of their system fail.

[T_aquaticus]

@colewd

My studies of cancer have been observations of loss of cellular regulation and from my perspective loss of functional information as regulation systems like the ubiquitin system have parts of their system fail.

If you define a change in gene regulation to be a loss then I would have to conclude that evolution requires a loss in information in order to evolve complex and well adapted organisms. You seemed to have painted yourself into a corner on this one.

[colewd (Bill Cole)]

@T_aquaticus

If you define a change in gene regulation to be a loss then I would have to conclude that evolution requires a loss in information in order to evolve complex and well adapted organisms. You seemed to have painted yourself into a corner on this one.

Multicellular organisms are capable of changes in how and when cells perform functions like cell division. Cancer appears to be enabling cell division at a stage that it should not like in a mature adult. Mutation can up regulate a transcriptional pathway that should be quite. It can also down regulate a regulation pathway that should be active.

[T_aquaticus]

@colewd

Multicellular organisms are capable of changes in how and when cells perform functions like cell division. Cancer appears to be enabling cell division at a stage that it should not like in a mature adult. Mutation can up regulate a transcriptional pathway that should be quite. It can also down regulate a regulation pathway that should be active.

Would you label any mutation that causes a change in gene regulation as a loss in function?