“At most, genomic analysis is showing genome form, function, and evolution to be much too complex to support any inflexible assumptions on either side.”

You can certainly believe whatever you like, but I remain agnostic pending further data.

Self-Defense and Freedom of Expression are often cited as supreme principles of advanced societies. I plead guilty to particular sensitivity to such issues, having lived through the butchered Revolution of 1956 in communist Hungary. (My sincerest gratitude to generous alternatives of oppression offered to my fellow-countrymen and women both by the USA and Canada – in retrospect I wish I had not been stuck in an ultracensored and ultrascontraselected confinement so long, till 1973 when I came as a postdoc to Stanford).

I am also grateful and happy for you that in your blog I have not experienced the “ideological bias and antagonism” that I do believe not only resulted in a quite unbelievable suppression of opinions (let alone denial of funds), but was contrary to the advancement of science beyond the “35 years of Junk DNA imprisonment”. I wrote this up to an “Obituary of Junk DNA”, but even that paper was rejected without review, similar to the one co-authored by about 30 IPGS Founders. (Nonetheless, that hastened the release of ENCODE Report from the planned September 2007 to June 14 2007).

My opinion is that my piece about “Malcolm’s story” (“Triumph and Tragedy”, after 5 years still never aired in the USA – I don’t know about Canadian release, if any) that in either “antagonistic blog” could have been easily published, due to my skills of fighting oppression, finally got published in both. (Quite a feat, in itself…)

Dear Malcolm (my lead-author in our paper based on Darwinian notion, but the F-word I don’t mention as promised), who has not been given any credit whatsoever (that I know of) in the cacophony of Post-ENCODE-Press and related blogs, may deserve at least as little while his tragically triumphant lifetime lasts.

pellionisz_at_junkdna.com

I was not aware that you had done this. I had tried to give you a fair chance to present your views in a proper scientific discussion, but the fact that you would resort to this makes me wish I hadn’t wasted my time on you.

Sure; I am a guest (only because we shared curiosity about explanation(s) on ultraconserved elements), and will of course honor your request.

Indeed, I intended “blog interference closed” with my “finally” answer before – but found direct questions to me afterwards and thought it would be both impolite and easy to misinterpret if I did not adequately answer. (Readers could stop after “No and No”).

The following might be of interest (just in, a reply to my inquiry to BI about the cavia porcellus projected genome size):

From: “Nicole Davis via RT” questions_at_broad.mit.edu
Date: Wed, 12 Sep 2007 09:19:22 -0400 (EDT)

Dear Dr. Pellionisz,

It’s a bit too early in the project to tell. From a snapshot of one of the last steps of the genome assembly, it looks like it is about 2.7Gb in size – but this could be artificially inflated because of high polymorphism rates in certain regions. The scientists who are working on this should know more definitively in a few weeks.

Hope this information is helpful to you.

Best wishes,
Nicole

So much for a short reply. When someone challenges you that the FractoGene approach has not been stated clearly in a peer-reviewed publication, you cite the Purkinje cell paper. When someone challenges the Purkinje cell paper, you say that it is not an exposition of the FractoGene approach.

Frankly, the rhetoric and obfuscation is getting exhausting.

I (and presumably my readers) would appreciate it if you didn’t repeat anything more about the FractoGene approach on this blog.

No and No. (In your required regretfully short format)

–

P.S.

“could you confirm that the Purkinje cell paper, and thus the FractoGene approach, assumes that the guinea pig genome size will be roughly intermediate between that of zebrafish and of human?”

To this imprecise question the answer should be a precise “No”. (No, I can not confirm an ill-formed statement poised as a question). First; from the question it is unclear if it refers to “Purkinje cell paper 1989″ [by Pellionisz] or “Purkinje cell paper 2006” [by Simons and Pellionisz]. Since the 1989 paper does not mention the zebrafish (both papers mention guinea pig and human), by inference one would think, your question refers to the 2006 paper. However, as any reader can tell, the FractoGene approach originated in 2002 and its prediction for fugu (not an assumption for guinea pig) originated in 2003, results started to trickle in 2004 about fugu, paper written in 2005 and peer-reviewed and published in 2006. Your question mixes up both the logic of timeline, and the targeted platforms).

“Specifically, does the FractoGene fail a test if guinea pig total genome size is NOT roughly 2Gb?”

To this imprecise question the answer should be a precise “No”.
First, the “Purkinje cell paper 2006” is not the FractoGene approach (see above timeline) but one prediction formulated based on the approach (for the arborization of Fugu PC) – and experimentation has proven supportive of the “fugu prediction”. Second, the peer-reviewed 2006 paper does not “assume” a “roughly 2Gb” for the guinea pig PC genome. In addition to the experimental support of the fugu PC prediction, the paper left question-marks on Fig. 4. both for the Danio (dendritic arborization) and Guinea Pig (genome sequencing result, reported in September, 2007 as “6x coverage ongoing”). It is very usual in the advancement of science that by answering a question further question-marks are raised. While on one hand I understand that sequencing is (still) expensive and takes time, what boggles my mind is that the zebrafish Purkinje arborization could have long been mapped and published (in its most primitive form a student can do the Golgi prep in a week).

Sometimes I wonder if scientists really want solution, or feel that “it is better business” as long as there is none. (Such that they can keep doing “experimentation as usual” without the disruption that paradigm-shifts typically invoke. Since I am quite familiar with this social phenomenon, the first prediction of FractoGene was deliberately composed *not* to require anything but the most pedestrian, routine experimentation). I love this blog, since it points out several controversies of the “establishment” – and this may be one, indeed. (So is the other that in the USA the best interest of medicine is not to cure people – because they would lose a “customer” – but it is better business to get a sick person hooked on some very expensive medicine that has to be taken for the rest of his/her life).

P.P.S.

If there are better explanation(s) for the vexing phenomena floated in this blog than FractoGene can provide, let’s hear them. Those who think FractoGene has predictive power for the fugu PC arborization only, see “Methylation prediction of FractoGene” (not limited to Purkinje cells).

P.P.P.S.

All through my professional life I collaborated with experimentalists both “at arms length” as well as “elbow to elbow”; resulting in a sizable number of peer-reviewed publications . I am presently doing so (of course, we don’t conduct competitive science on blogs), and my openness to collective efforts has been widely expressed (also in Society format), and reiterated herein. The array of challenges has been enormous and “post-Encode” is blown to staggering and humbling. Maybe we should not overly punish those who think outside the box – since suddenly we all are outside the box. Worse, any of us may be diagnosed of some “Junk DNA diseases” of which some I know are actually dying. This explains my more acute interest these days in “fractal defects” in regulatory DNA than the zebrafish PC arbor (that I have seen already, anyway).

pellionisz_at_junkdna.com

YES / NO

Specifically, does the FractoGene fail a test if guinea pig total genome size is NOT roughly 2Gb?

YES / NO

I just want to make sure I am clear on what your approach assumes/requires.

“if it is your prediction that the Cavia genome will be around 2Gb according to the expectations of FractoGene, then this is good because it is testable”

Yepp, the “Fugu cerebellum” paper presented a suitable platform (Purkinje neuron), and an approach with an algorithmic handle (fractals) to provide predictions both for the general trend of increasing fractal complexity (and cell size) with genome size, where the algorithmic explanation (fractal growth) allows for the observed huge deviations (rapidly or slowly converging iterative process). For the Fugu Purkinje cell the genome size (1/8 of human) predicted a rudimentary P-cell arborization compared to the human. In case of the two interim species (guinea pig and zebra fish) in one case the P-cell was known but the genome wasn’t, for the zebra fish, the other way around. Now with these quantitative data becoming available neither peer-review publication nor testability are questionable. (On another blog I outlined an experimental protocol way beyond ordinary means of a traditional “not-transdisciplinary” University Department – but more suitable for a Center of PostGenetics.

My blog interference only wished to point out that (a) those who want to know a viable approach were informed about availability (the fractal approach is also helpful to resolve the “mystery” of ultraconserved elements)and (b) help to show “non-obviousness”, (c) discourage people to later say “oh, sure, but it is nothing new – we all knew that all along”.

To show that all is not only about “FractoGene”, I finally mention that there is a rapidly escalating number of scientists who have stepped over the “flabbergasted” stage some time ago and are working feverishly on algorithmic approaches (see under “PostGenetics”). For those considering deep math a friend, I highly recommend Michael F. Barnsley’s “SuperFractals” (2006).

pellionisz_at_junkdna.com

You are referring to a rather fragmentary preliminary assembly of the Cavia genome, not to estimates of actual genome size. However, if it is your prediction that the Cavia genome will be around 2Gb according to the expectations of FractoGene, then this is good because it is testable.

It is my opinion that you need to present a clear exposition of the “FractoGene” approach and its predictions, and that this needs to be subjected to peer review and backed up with far more data. I said you could suggest me as a reviewer for this new paper if you wanted. In other words, I am willing to consider the idea if it is presented properly. That is not to say that I think there is much merit to it based on what I have seen, only that I am keeping an open mind. However, if you decline to subject the approach to proper peer review and to provide sufficient data, then I will have little choice but to reject the FractoGene approach along with many other ideas about “function” for non-coding DNA.

The Purkinje cell paper provides a very minimal discussion of the approach. If it is “highly technical”, then you need to make it very clear so that others can evaluate what it states and predicts, and you need a lot of data to support it. I don’t think even the small dataset you selected supports what you claim, but again please clarify for me precisely what genome size you would predict for Cavia and several other groups that have not been measured yet. This is how you test a hypothesis properly.

In short, until you are willing to present the model clearly in a peer-reviewed paper, to make explicit and testable predictions, and to provide data, I am not interested in discussing the “FractoGene” approach any further and I would appreciate it if you would refrain from repeating the same claims over and over on my discussion forums.