Junk DNA Surgery - Therapy up to a Cure for Genome Regulation Diseases

Pellionisz' FractoGene, 2002


Eric Lander (Science Adviser to the President and Director of Broad Institute) et al. delivered the message
on Science Magazine cover (Oct. 9, 2009) to the effect:

"Mr. President; The Genome is Fractal !"





For a comprehensive peer-reviewed essay on the geometrical approach, see the multiple award-winning publication:
Recursive Genome Function or the Cerebellum: Geometric Unification of Neuroscience and Genomics
Springer, In Press, Supplementary Material,
Submitted [just too early to contain the above "Proof of Concept"] on October 20, Accepted Nov. 1. 2011


Chromosome structure fractal defects implicated in cancer

In about half a year we have seen three independent experimental Proof of Concept studies that fractal defects, the largest of which are Copy Number Variations, are implicated in cancer.

The first Nature study appeared by a HARVARD/MIT/BROAD/DANA-FARBER group in Boston, USA (4 authors)

The second Nature study carried the concept abroad to SANGER INSTITUTE in Cambridge, UK (63 authors, linked to 10 countries; UK, Belgium, Norway, China, Singapore, The Netherlands, Australia, Canada, USA, France)

The third Nature study was completed in USA MIDWEST, MICHIGAN, ANN ARBOR (27 authors, affiliation linked also to to India)

The above three PoC Nature papers are the easiest to understand by visualization of the rotating 3D Hilbert-curve of DNA-fractal, that is transparent in its pristine form, but Copy Number Alterations clog the transparency, thus the functional proximity of physically distant parts of the DNA, to be read in a parallel manner, is disrupted by fractal defects.

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Now a fourth, PNAS study led by a NEW YORK CITY Institute, endowed by HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud of SAUDI ARABIA, also linked to the Mount Sinai Hospital and an affiliation in Italy (14 authors), the paper edited by Eric Lander (The Broad Institute) generalized the above findings to show that chromosome structure fractal defects are implicated in cancer. This study is not so easy to visualize as it pertains to the genome regulation aberrations at the DNA chromatin level (for early 2008 visualizations, see YouTube [at 30:26], cf. Fig. 6. of The Principle of Recursive Genome Function). The PNAS paper uses the analysis of functional proximities (by the properly cited experimental Hi-C method of Lieberman-Aiden et al, 2009, co-authored by Eric Lander, the paper hallmarked by the Science Magazine displaying on its cover the Hilbert-curve). It is interesting that the edited paper states in its Supplement info that "Interaction Data Support the Fractal Globule Model of Nuclear Organization".

[The above can be discussed in FaceBook page of Andras Pellionisz, and Tweeted @HolGenTech]

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In half a year, third independent experimental Proof of Concept that fractal defect of Copy Number Variation is implicated in cancer

The mutational landscape of lethal castration-resistant prostate cancer

Nature (2012) doi:10.1038/nature11125

Characterization of the prostate cancer transcriptome and genome has identified chromosomal rearrangements and copy number gains and losses, including ETS gene family fusions, PTEN loss and androgen receptor (AR) amplification, which drive prostate cancer development and progression to lethal, metastatic castration-resistant prostate cancer (CRPC)1. However, less is known about the role of mutations2, 3, 4. Here we sequenced the exomes of 50 lethal, heavily pre-treated metastatic CRPCs obtained at rapid autopsy (including three different foci from the same patient) and 11 treatment-naive, high-grade localized prostate cancers. We identified low overall mutation rates even in heavily treated CRPCs (2.00 per megabase) and confirmed the monoclonal origin of lethal CRPC. Integrating exome copy number analysis identified disruptions of CHD1 that define a subtype of ETS gene family fusion-negative prostate cancer. Similarly, we demonstrate that ETS2, which is deleted in approximately one-third of CRPCs (commonly through TMPRSS2:ERG fusions), is also deregulated through mutation. Furthermore, we identified recurrent mutations in multiple chromatin- and histone-modifying genes, including MLL2 (mutated in 8.6% of prostate cancers), and demonstrate interaction of the MLL complex with the AR, which is required for AR-mediated signalling. We also identified novel recurrent mutations in the AR collaborating factor FOXA1, which is mutated in 5 of 147 (3.4%) prostate cancers (both untreated localized prostate cancer and CRPC), and showed that mutated FOXA1 represses androgen signalling and increases tumour growth. Proteins that physically interact with the AR, such as the ERG gene fusion product, FOXA1, MLL2, UTX (also known as KDM6A) and ASXL1 were found to be mutated in CRPC. In summary, we describe the mutational landscape of a heavily treated metastatic cancer, identify novel mechanisms of AR signalling deregulated in prostate cancer, and prioritize candidates for future study.

[Copy Number Variations - the largest pieces of fractal defects - clog the transparency of the delicate fractal Hilbert-curve of DNA. In half a year, a Boston (MIT-Harvard-Broad-Dana Farber), a Cambridge UK (Sanger) and now a Michigan-group provides, what appears to be an undisputable evidence that massive fractal defects disrupt genome regulation in cancer. Now the question is no longer "if a Proof of Concept" is clinched, but only a matter of ramping up the fractal interpretation of the analysis of derailed genome regulation - Pellionisz]

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A Decade after Genomics was Declared to be Informatics; Vistas by Andras Pellionisz (Part II)

An Avalanche of Independent Experimental Proofs of Concept that Intact or Defective Fractal Genome Governs Physiological or Pathological Growth of Organs, Organelles and Organisms; FractoGene (2002)

Pellionisz’ “FractoGene” approach receives massive independent experimental “Proof of Concept”, published in top peer-reviewed journals (25-29, 31 in 2011 and 2012). POC-s stream within a single decade since inception and in spite of a need to shred both prevailing mistaken axioms of genomics defended with (ad hominem) “tools and nails” by ossified detractors of the old establishment.

While upon arrival of the first full human DNA (2000) it became evident that the old hypotheses of “Genes and Junk” were debased by the obvious lack of expected genes, moreover a fractal hypothesis was already seeded (1-2), Eric Lander declared a conceptual vacuum of “hypothesis free search for genes” (3). Nobody dared issuing any attacks against him, especially not “ad hominem” slur for this, since it at least permitted a “no brainer” activity to supposedly last forever. As a mathematician he knew that, without scientific hypotheses proving or disproving by rigorous check their validity, research degenerated into a serendipituous mode - in English, to the horrendously expensive “brute force” – much like as a ship that randomly navigates without a compass; see the famous bestseller of Thomas Kuhn entitled “The Structure of Scientific Revolutions”.

It took less than a decade, when Dr. Pellionisz already published his Principle of Recursive Genome Function (12) and he was invited by George Church to present it in Cold Spring Harbor (17) that the Science Advisor to the President, Eric Lander put the fractal concept of genome on the cover of Science magazine (18).

The ensuing tumultuous the three years brought endorsements based on due diligence: “Of most interest to me are Andras Pellionisz’ ideas around the fractal nature of genomes and how disruptions in such structure may drive phenotypic variation ... The detection of these structure and subsequent determination of their association with disease are computationally intense problems. If something like this were shown to be true (disruptions in the fractal structures lead to phenotypic change), it would be truly revolutionary” (Schadt E, written communication to prominent IT industry).

Now the long-requested Proofs of Concept are in, the trickle of first findings rapidly becoming an avalanche of massive evidence (instead of “hypothesis-free search for genes”). In (18) and (25) with personal co-authorship of the Science Advisor to the President, it is shown that the unique fractal property of ultra-dense and knotless folding of DNA also has a “see through” feature (bringing to functional proximity all parts of the DNA, in a parallel manner) – but this “transparency” is lost e.g. by the fractal defect of a copy numuber alteration (26).

Along with fervent experimental-theoretical research (18-31) it is now recognized that Dr. Pellionisz “... revolutionized the biological sciences with geometrization of neuroscience and genetics. This has been achieved by application of recursion Algorithms based on the principle that each state of the system is deduced from its previous states just like in algebraic series” (30). Germany embraced his geometrization by the Senior Distinguished American Scientist Humboldt Prize, was invited as Keynote Speaker on FractoGene (2003 Florida), to Hungary (2006), to Cold Spring Harbor (2009), India embraced his fractal concept by Guest of Honor and Keynote Lectures and Decoration of his Lifetime Achievement (2012, Hyderabad and Trivandrum), an is presently invited to Italy (Bologna, June 2012). Geometrization of neuroscience drew its consequences on philosophy in Neuroscience by Patricia Churchland (Neurophilosophy, MIT) and on Unified Neuroscience and Genomics in 2012 by Niraj Kumar in India (30). Further, the roadplan outlined e.g. in personalized medicine, most notably cancer, (32) became a linchpin in fierce global competition of scalable full business models of emerging countries.

Most concpicuously, cancer may or may not become the first disease solved by computers, but at this time it might take a veritable computer illiterate to dream that the “genome disease” (cancer) can ever be solved without the leadership of those with software enabling algorithmic hypotheses, now within a single decade way beyond the POC stage.

Timeline

(1) 1989 Pellionisz AJ, Neural geometry: towards a fractal model of neurons. In: Cotterill RMJ (ed) Models of brain function. Cambridge University Press, Cambridge, pp 453–464. http://www.junkdna.com/pellionisz_fractal_purkinje_neuron_1989.pdf

(2) 1993 Grosberg A, Rabin Y, Havlin S, Neer A (1993) Crumpled globule model of the three-dimensional structure of DNA. Europhys Lett 23:373–378. http://havlin.biu.ac.il/PS/scan189.pdf

(3) 2000 Lander E. (2000) A Hypothesis-free Search for Genes. Keystone Millenium Meeting: A Trends Guide (Page 48 in Neurosciences at the Postgenomic Era, by Jacques Mallet, Yves Christen, Springer, 2003)

(4) 2002 Pellionisz A; FractoGene Provisional submission to USPTO
http://www.fractogene.com

(5) 2002 Plotkin H. (2002) Junk DNA Revisited. Silicon Valley startup claims to have unlocked a key to its hidden language. San Francisco Chronicle, http://www.junkdna.com/plotkin.htm

(6) 2003 Pellionisz A; FractoGene Regular submission to USPTO
http://www.fractogene.com

(7) 2003 Pellionisz A. (2003) FractoGene Design-Tool for Protein-Based Self-Assembling Nanostructures, Materials and Applications Keynote Lecture of the 204th Electrochemical Society, pp. 1195 http://www.fractogene.com/1195.pdf

(8) 2006 Pellionisz, A. (2006) PostGenetics: Genetics beyond Genes. The journey of discovery of the function of "junk" DNA. Peer-invited and peer-reviewed Keynote lecture at "European Inaugural of the International PostGenetics Society", 12. October, 2006, Budapest, Hungary, a Satellite to the International Congress of Immunogenomics and Immunomics, pp. 219., BCII2006

(9) 2006 Simons M, Pellionisz A (2006a) Genomics, morphogenesis and biophysics: triangulation of purkinje cell development. The Cerebellum 5(1):27–35. http://www.junkdna.com/fractogene/05_simons_pellionisz.pdf

(10) 2006 Simons M, Pellionisz A (2006b) Implications of fractal organization of DNA on disease risk genomic mapping and immune function analysis. Australasian and Southeast Asian Tissue Typing Association. In: 30th scientific meeting 22–24 Nov 2006, Chiangmai. http://www.junkdna.com/fractogene/06_simons_pellionisz.html

(11) 2007 Pellionisz A; FractoGene CIP submission to USPTO
http://www.fractogene.com

(12) 2008 The Principle of Recursive Genome Function, Springer, Cerebellum. 2008;7(3):348-59.
Full .pdf http://ww.junkdna.com/pellionisz_principle_of_recursive_genome_function.pdf
Supplementary material http://www.junkdna.com/pellionisz_principle

(13) 2008 October 30, Is IT Ready for the Dreaded DNA Data Deluge? YouTube
http://www.youtube.com/watch?v=WJMFuc75V_w approaching 14 thousand views

(14) 2008 Shapshak P, Chiappelli, F, Commins D, Singer E, Levine AJ, Somboonwit C, Minagar A, Pellionisz, A (2008) Molecular epigenetics, chromatin, and NeuroAIDS/HIV: translational implications. Bioinformation 3(1):53–57. PMCID: PMC2586134

(15) 2008 Chiappelli F, Shapshak P, Commins D, Singer E, Minagar E, Oluwadara O et al (2008) Molecular epigenetics, chromatin, and NeuroAIDS/HIV: immunopathological implications. Bioinformation 3(1):47–52.

(16) 2009 Cartieri FJ (2009) Darwinism and Lamarckism before and after Weisman: a historical, philosophical, and methodological analysis. University of Pittsburg, pp 1–54.

(17) 2009 Pellionisz A. (2009 September 16) From the Principle of Recursive Genome Function of HoloGenome Regulation by Personal Genome Computers (Cold Spring Harbor Labs “Personal Genomes II.” invited by George Church)

(18) 2009 Erez Lieberman-Aiden, Nynke L. van Berkum, Louise Williams, Maxim Imakaev, Tobias Ragoczy, Agnes Telling, Ido Amit, Bryan R. Lajoie, Peter J. Sabo, Michael O. Dorschner, Richard Sandstrom, Bradley Bernstein, M. A. Bender, Mark Groudine, Andreas Gnirke, John Stamatoyannopoulos, Leonid A. Mirny, Eric S. Lander, Job Dekker (2009 October 9) The comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326. doi: 10.1126/science.1181369
Full .pdf at http://www.cbcb.umd.edu/~hcorrada/CMSC858B/readings/Hi-C_2009.pdf

(19) 2010 Perez JC (2010) Codon population in single-stranded whole human genome DNA are fractal and fine-tuned by the Golden Ration 1.618. Interdiscip Sci: Comput Life Sci 2(3):228–340. doi:10.1007/s12539-010-0022-0.

(20) 2010 Arneth BM (2010) Sequence variability and sequence evolution: An explanation of molecular polymorphisms and why many molecular structures can be preserved although they are not predominant. DNA Cell Biol 29(10):571–576. doi:10.1089/dna.2009.0942

(21) 2010 Oller JW (2010) The antithesis of entropy: Biosemiotic communication from genetics to human language with special emphasis on the Iimmune systems. Entropy 12:631–705. doi:10.3390/e12040631. http://www.mdpi.com/1099-4300/12/4/631/pdf

(22) 2011 Stagnaro S (2011) Glycocalix quantum-biophysical-semeiotic evaluation plays a central role in demonstration of water memory-information. http://www.sisbq.org/uploads/5/6/8/7/5687930/wmi_glycocalyx.pdf

(23) 2011 Stagnaro S, Caramel S (2011) A new way of therapy based on water memory-information: the Quantum biophysical approach. http://www.sisbq.org/uploads/5/6/8/7/5687930/qbtherapy.pdf

(24) 2011 Elnitski L, Piontkivska H, Welch JR (2011) In: Fedorov A, Fedorava L (eds) Advances in genomic sequence analysis and pattern discovery, Chapter 3. Science, engineering and biology informatics, vol 7. World Scientific, Singapore, pp 65–93

(25) 2011 The genomic complexity of primary human prostate cancer (2011) Nature. 470, 214-220, doi:10.1038/nature09744 Michael F. Berger, Michael S. Lawrence, Francesca Demichelis, Yotam Drier, Kristian Cibulskis, Andrey Y. Sivachenko, Andrea Sboner, Raquel Esgueva, Dorothee Pflueger, Carrie Sougnez, Robert Onofrio, Scott L. Carter, Kyung Park, Lukas Habegger, Lauren Ambrogio, Timothy Fennell, Melissa Parkin, Gordon Saksena, Douglas Voet, Alex H. Ramos, Trevor J. Pugh, Jane Wilkinson, Sheila Fisher, Wendy Winckler, Scott Mahan, Kristin Ardlie, Jennifer Baldwin, Jonathan W. Simons, Naoki Kitabayashi, Theresa Y. MacDonald, Philip W. Kantoff, Lynda Chin, Stacey B. Gabriel, Mark B. Gerstein, Todd R. Golub, Matthew Meyerson, Ashutosh Tewari, Eric S. Lander, Gad Getz, Mark A. Rubin, Levi A. Garraway
Full .pdf at http://www.nature.com/nature/journal/v470/n7333/full/nature09744.html

(26) 2011 High order chromatin architecture shapes the landscape of chromosomal alterations in cancer (2011) Fundenberg G, Getz G, Meyerson M, Mirny L.A. http://www.nature.com/nbt/journal/v29/n12/full/nbt.2049.html

(27) 2011 The genetic code, 8-dimensional hypercomplex numbers and dyadic shifts. (2011) Petoukhov, Sergey V. International Conference on Bioinformatics & Computational Biology (Las Vegas, USA, July 18-21, 2011) http://arxiv.org/ftp/arxiv/papers/1102/1102.3596.pdf

(28) 2012 February 17 Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure (2012) Yoshinori Nishino, Mikhail Eltsov, Yasumasa Joti, Kazuki Ito, Hideaki Takata, Yukio Takahashi, Saera Hihara, Achilleas S Frangakis, Naoko Imamoto, Tetsuya Ishikawa and Kazuhiro Maeshima
http://www.ncbi.nlm.nih.gov/pubmed/22343941

(29) 2012 February 17 Toward Convergence of Experimental Studies and Theoretical Modeling of the Chromatin Fiber (2012) Tamar Schlick, Jeff Hayes and Sergei Grigoryev, doi: 10.1074/jbc.R111.305763 February 17, 2012 The Journal of Biological Chemistry, 287, 5183-5191.
http://www.jbc.org/content/287/8/5183.abstract

(30) 2012 March 11, Niraj Kumar (2012) Sryantra – Mathematical Properties. Geophilosophy of India and Sriyantra.
http://ariseasia.blogspot.com/2012/03/sriyantra-mathematical-properties.html

(31) 2012 March 13 Human mitotic chromosome structure: what happened to the 30-nm fibre? Jeffrey C Hansen The EMBO Journal (2012) 31, 1621–1623. doi:10.1038/emboj.2012.66; Published online 13 March 2012
http://www.nature.com/emboj/journal/v31/n7/full/emboj201266a.html

(32) 2012 Andras J. Pellionisz, Roy Graham, Peter A. Pellionisz and Jean-Claude Perez (In Press) Recursive Genome Function of the Cerebellum: Geometric Unification of Neuroscience and Genomics. In: Springer Handbook; "The Cerebellum and Cerebellar Disorders", Ed. by M. Manto. Submitted October 20, Accepted November 1, 2011, (In Press)
http://www.junkdna.com/pellionisz_unification/
Full .pdf http://www.fractal.org/Geometric-unification.pdf

Legacy

It is a twist of life that Ohno’s scientifically erroneous notion “So much ‘Junk’ in Our Genome” (1972), where his original, meant-to-be “scientific” statement that almost all of our DNA was there for “the importance of doing nothing”, see page 367 was misinterpreted, like other half-baked assumptions such as “Central Dogma”, that together set back Genomics by half a Century. As a further and ultimate irony, John Mattick and Malcolm Simons arrived at their respective final conclusions about the same time when the superseeding fractal paradigm prevailed. Dear Malcolm Simons passed away January 25th, 2012 in his 73rd year unrecognized outside the 66 Founders of International Hologenomics Society (Founders overlaping with the list below), where he was the Honorary Chairman.  Very soon after, Dr. Mattick received a lifetime-award from HUGO on March 12, 2012.

Finally, it bespeaks volumes of ignorance caused by lack of domain expertise in abstract sciences coupled with remarkable arrogance shrouded by thick denial, that a detractor calls the awarded Dr. Mattick “stupid and irrational”: “I am criticizing Mattick's ideas, which I find to be quite silly and irrational. Saying that Mattick is stupid and irrational because of what he writes and draws is not an ad hominem fallacy”. Dr. Mattick, who heroically struggles with a mathematical interpretation of the RNA system, may be comforted by the well-known history that Dr. Barbara McClintock was also called a “kook” by similar detractors – and awarded by a Nobel Prize some 40 years after her paradigm-shift.

Partial List of Personal Commitments in the First Decade

Andras J. Pellionisz, Roy Graham, Peter A. Pellionisz, Jean-Claude Perez, Sergey V. Petoukhov, Michael F. Berger, Michael S. Lawrence, Francesca Demichelis, Yotam Drier, Kristian Cibulskis, Andrey Y. Sivachenko, Andrea Sboner, Raquel Esgueva, Dorothee Pflueger, Carrie Sougnez, Robert Onofrio, Scott L. Carter, Kyung Park, Lukas Habegger, Lauren Ambrogio, Timothy Fennell, Melissa Parkin, Gordon Saksena, Douglas Voet, Alex H. Ramos, Trevor J. Pugh, Jane Wilkinson, Sheila Fisher, Wendy Winckler, Scott Mahan, Kristin Ardlie, Jennifer Baldwin, Jonathan W. Simons, Naoki Kitabayashi, Theresa Y. MacDonald, Philip W. Kantoff, Lynda Chin, Stacey B. Gabriel, Mark B. Gerstein, Todd R. Golub, Matthew Meyerson, Ashutosh Tewari, Eric S. Lander, Gad Getz, Mark A. Rubin, Levi A. Garraway, Grosberg A, Rabin Y, Havlin S, Neer A, Plotkin Hal, Simons J. Malcolm, Shapshak P, Chiappelli, F, Commins D, Singer E, Levine AJ, Somboonwit C, Minagar A, Oluwadara O, Cartieri FJ, Erez Lieberman-Aiden, Nynke L. van Berkum, Louise Williams, Maxim Imakaev, Tobias Ragoczy, Agnes Telling, Ido Amit, Bryan R. Lajoie, Peter J. Sabo, Michael O. Dorschner, Richard Sandstrom, Bradley Bernstein, M. A. Bender, Mark Groudine, Andreas Gnirke, John Stamatoyannopoulos, Leonid A. Mirny, Eric S. Lander, Job Dekker, Arneth BM, Oller JW, Stagnaro S, Caramel S, Elnitski L, Piontkivska H, Welch JR, Fundenberg G, Getz G, Meyerson M, Mirny L.A. Yoshinori Nishino, Mikhail Eltsov, Yasumasa Joti, Kazuki Ito, Hideaki Takata, Yukio Takahashi, Saera Hihara, Achilleas S Frangakis, Naoko Imamoto, Tetsuya Ishikawa and Kazuhiro Maeshima, Jeffrey C Hansen, Tamar Schlick, Jeff Hayes, Sergei Grigoryev, Church GM, Schadt E, Ruis J, Flanagan B, Audrey S M Teo, Pramila N Ariyaratne, Naoto Takahashi, Kenichi Sawada, Yao Fei, Sheila Soh, Wah Heng Lee, John W J Huang, John C Allen Jr, Xing Yi Woo, Niranjan Nagarajan, Vikrant Kumar, Anbupalam Thalamuthu, Wan Ting Poh, Ai Leen Ang, Hae Tha Mya, Gee Fung How, Li Yi Yang, Liang Piu Koh, Balram Chowbay, Chia-Tien Chang, Veera S Nadarajan, Wee Joo Chng, Hein Than, Lay Cheng Lim, Yeow Tee Goh, Shenli Zhang, Dianne Poh, Patrick Tan, Ju-Ee Seet, Mei-Kim Ang, Noan-Minh Chau, Quan-Sing Ng, Daniel S W Tan, Manabu Soda, Kazutoshi Isobe, Markus M Nöthen, Tien Y Wong, Atif Shahab, Xiaoan Ruan, Valère Cacheux-Rataboul, Wing-Kin Sung, Eng Huat Tan, Yasushi Yatabe, Hiroyuki Mano, Ross A Soo, Tan Min Chin, Wan-Teck Lim, Yijun Ruan, S Tiong Ong, Niraj Kumar

[This entry can be discussed on the FaceBook page of Andras Pellionisz - full .pdf copies may be requested - AJP]

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Well, This Is Awkward

Genomeweb
April 18, 2012

The Walrus magazine's Mark Czarnecki says that "to comprehend genomes is to begin to unlock the mysteries of life." But that, of course, has been tricky. In the meantime, he says, society has found itself "lost on the gene map" — while [some] researchers have not yet nailed down their interpretations of the human genome, direct-to-consumer firms are hawking genetic tests and that offer to "detail your risks for a menu of diseases." All the while, researchers have struggled to understand the ethical, legal, and social implications of genomics.

Now, Czarnecki says, "with whole-genome sequencing providing so much data that is so little understood, making the best ethical choice is more difficult than ever." He goes on to add that "as the demand for whole-genome sequencing grows, so will profits, but the big money in personalized medicine will come from the development of treatments. … A given mutation on a person's genome may not necessarily express as a malignant disease, so identifying the probability of a multigenic disease is extremely challenging."

Overall, Czarnecki says that at present, "the human genome is still a vast catalogue of the unknown and scarcely known," and that "as medical science struggles to apply these new discoveries to society's benefit, human genome research, now unstoppable, continues to evolve."

[Indeed, it is kind of "awkward". We know ever since the mouse was fully sequenced a decade ago (2002) that our (human) "genes" are 98% identical to those of the mice; thus "upon arrival" the half-a-century assumption that the genome rotates around the "genes", was dead. Some know that in the same year, a decade ago, Leroy Hood declared in 2002 that "Genomics=Informatics" and thus must be approached from some "Systems Biology" viewpoint (invoking Ludwig von Berthalanffy, 1934). Of course, but WHAT SYSTEM? Without system identification systems biology would be rendered serendipitous (in plain English; horrendously expensive). Thomas Kuhn recalled in his famous bestseller "The Structure of Scientific Revolutions" that through the history of science, amassing data alone was never enough - it always underwent the transformative revelation of what the data actually mean. Some recall that in 2002 Pellionisz' "FractoGene" (at that time a "double lucid heresy" flying in the face of the two prevailing dogmas) identified that "the genome is a fractal systems, governing the fractal growth of organelles, organs and organisms" (like normal lungs, brain cells, etc., and cancerous tumors). Has anyone ever seen a fractal object generating another fractal object? Here is some little help: "Clouds are not spheres... nor does lightning travel in a straight line" said the now late giant, Mandelbrot. To remind you having seen "fractals generating fractals" here is my rendering:

FractoGene: "Fractal Genome governs growth of fractal organelles, organs and organisms" (Pellionisz, 2002 see also Geometric Unification of Neuroscience and Genomics, in Press 2012)

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Join viewers from pivotal (sub)continents (USA, India) that an over 40 months warning was issued to prevent a historical unsustainability.

[As usual, there are always workers who believe that the role of science is to provide more data (not so, claimed Thomas Kuhn in his classic bestseller, "The Structure of Scientific Revolutions"). The present cop out is to claim that the science of genomics might be "hypothesis free". Eric Topol points out the self-contradiction of the latest genomic misnomer in his present bestseller. Just because some do not have any hypothesis of e.g. what the new definition of "gene" might be (replacing the old one made obsolete by ENCODE), does not mean that the "FractoGene" algorithmic hypothesis has to move over because of the pushy brute force of (ultra expensive) "big science" schemes. This issue can be debated on the FaceBook page of Andras Pellionisz]

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A Decade after Genomics was Declared to be Informatics; Vistas by Andras Pellionisz (Part I)

In 2002, a pair of seminal notions were introduced, just months after the much-heralded "solves it all" misnomer of "cracking the code" (that was at best a $3Bn Big Science coup, resulting in a crude first draft of revealing - not decyphering - a composite human genome), by Leroy Hood and Andras Pellionisz (separately). Lee Hood, in his Kyoto Prize lecture (2002) declared that "Genomics became Informatics" and thus proposed that it should be approached by System Theory (of Ludwig von Bertalanffy, 1934). I went in the same year of 2002 on written record of USPTO, since no peer-reviewed forum would have accepted his "double lucid heresy", by System Identification; that is, "The genome is a fractal system, that governs fractal growth of organelles, organs and organisms; FractoGene" (Pellionisz, 2002).

After a tumultuous Decade, in a series of notes here Dr. Pellionisz provides the "vistas" how the initial axioms led to conquering the half-a-Century old interlocking (false) Dogmas (the frighteningly unsophisticated "Central Dogma" and comparably simplistic falsehood of "Junk DNA"), towards a breakthrough of today, when both an advanced mathematical treatise of Unification of Neuroscience and Genomics, In Press, (featuring the RNA system as a "genomic cerebellum"), plus at least "the magic trio" of independent experimental Proof of Concept is in high-ranking peer-reviewed journals to validate that "fractal defects cause hereditary diseases" like cancers.

While in the USA "the priesthood of the establishment" (to use the jargon of Eric Topol from his book of The Creative Disruption of Medicine) has fought this revolution all the way (and beyond), Drs. George Church and Eric Schadt have grown to acknowledge my effort by my name, and implicitly Drs. Eric Lander and his numerous co-authors recognize the cardinal notion of fractal genome - as e.g. sophisticated outsiders llike Ray Kurzweil have immediately did so.

Lately, and entire Subcontinent (of India) provided support to a global and scalable business model based on fractal genome and scientifically targeted search for fractal defects as root causes of hereditary diseases. The illustration below alludes the immediate realization that even if not all DNA is fractal, "the DNA of Indian architecture" is based on self-similar repetition, it is fractal.

While NONE of the methods of science can ever be "hypothesis-free" (as Eric Topol alludes in his bestseller to the inherent hypocrisy), the software-enabling mathematical (fractal) theory is particularly well above the level of usually ultra-expensive "brute force approaches" - that would further enhance "unsustainable trends" of the PostModern Industrialization of Genomics.

[To be continued; the issue can be debated on the FaceBook page of Andras Pellionisz]

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The medical world is holding its breath, waiting for the revolution. It will be here any minute. Definitely by the end of the decade. Or perhaps it will take a little longer than that, but seriously, it’s right around the corner. More or less.

That’s the genomics revolution, with its promise of treatment focused on the individual rather than the group. At last, patients will be more than the product of their age, sex, ethnicity, illnesses and bad habits; treatments will be aimed like a laser at their personal genetic particulars, and if those genes are not quite what they should be, then those genes will be fixed.

Over the last few years, various breathless visions of this therapeutic future have been written out for public admiration. A particularly readable and comprehensive version can be found in Dr. Eric J. Topol’s new book, “The Creative Destruction of Medicine.”

Dr. Topol, a cardiologist and researcher at the Scripps Research Institute with the energy of 10 (if his prose style and his honor-laden biography are any indication), dispenses in short order with our current population-based medical strategies. They are wasteful and inexact, he points out, often marginally beneficial to the group and downright harmful to the individual.

He presents an array of far better ideas, a few now actually being practiced in rudimentary form. These include pharmacogenomics, in which specific genes that govern responses to medications are routinely assayed, and cancer treatments that probe tumors for specific genetic targets rather than relying on standard chemotherapy.

But that’s not all: Dr. Topol also points out that soon a person’s precise genetic data will be augmented by an extraordinary wealth of other digital data (provided by, say, the continuous monitoring of blood pressure, pulse and mood, and a variety of ultra-precise scans). The outcome will be nothing short of a new “science of individuality,” one that defines individuals “at a more granular and molecular level than ever imaginable.”

Praise:

The Creative Destruction of Medicine by Eric Topol

“A must-read that lays out a road map for how new technologies in genomics, information technology, and mobile medicine may completely change the way we treat and prevent illness. It’s highly recommended, because Topol has a unique vantage point: he’s one of the few researchers to have played an important role in the old, mass-market medicine world and the newer, genetically focused one.”

Forbes

“Topol demonstrates how the digital revolution can be used to change individual care and prevention, and even the economics of American healthcare. From cell phones that automatically collect medical data, to biosensors, advanced imaging, individualized prescriptions and gene-specific drugs, Topol’s book leads readers through science-fiction-sounding scenarios that may soon be a reality.”

Salon


“The Creative Destruction of Medicine - an allusion to economist Joseph Schumpeter’s description of ‘creative destruction’ as an engine of business innovation is a venture capitalist’s delight, describing dozens of medical technologies that show great promise. The book also provides colorful anecdotes about Dr. Topol’s own sampling of these products, as both a doctor and stand-in patient…. [The book’s] most important contributions are in portraying how medical innovation will coalesce to change clinical practice and what the coming changes mean for today’s policy debates…. In Dr. Topol’s vision, innovation that enables real-time diagnosis and personalized treatments is a certainty, though not because reluctant or ‘sclerotic’ doctors accept it or because Washington wills it into being. A seductive technology that works like a dream and improves lives will set off a consumer clamor, whether the new tool is an iPhone 4S or an implantable blood-sugar meter.”

Wall Street Journal

“Topol does an excellent job of explaining all, and his enthusiasm for the possibilities of what the future holds is infectious. It can only be hoped, as the convergence he so convincingly predicts materializes, that the barriers erected by the gatekeepers of yesterday’s paradigms will be easily dismantled so as not to impede the benefits it promises.”

Boston Globe

“An eye opening account of why conventional medicine is doomed…. [C]ompelling stuff…. [T]he book provides an excellent summary of the current state of medical genetics and how fast it is progressing, with examples that may surprise even those working in medicine.”

New Scientist

“Topol makes the case that the masses of macro-data at our fingertips (literally), will unleash micro-level diagnostic and curative solutions never before imagined or hypothesized. It’s a remarkably bold vision that many experienced physicians will call naïve since it defies conventional wisdom - which is precisely why I think he’s on to something big.”

Longwoods eLetter

[A] prescient view of the near future of medicine…. Every patient should read this book in order to understand the rapidly evolving role in they play in their own care…. The Creative Destruction of Medicine is a call to action for doctors and patients alike. We must see our world and our job as doctor and patient very differently. In a profession so uncertain of its future, we need precisely the vision and critical dialog offered here…. I suspect that 150 years from now when historians are looking back at the most dramatic flexion point in medicine’s history they’ll reference this book as one of the first to identify the start of medicine’s creative destruction.”

Bryan Vartabedian, MD, 33 Charts.com

Modern medicine needs a makeover. Topol, of the Scripps Research Institute, believes the process begins with embracing the digital world. His plan involves genomics, wireless biosensors, advanced imaging of the body, and highly developed health information technology. Smartphones will tie these elements together to make health care individualized,efficient, and accessible. Topol foresees a future medical landscape characterized by virtual house calls, remote monitoring, and a lessened need for hospitals.”

Sharon Begley, Kirkus Reviews

“The book makes a compelling case for the role of digital technology in bringing nimbleness to ossified healthcare systems worldwide.”

Calestous Juma, Harvard Kennedy School

Our sequencing of the human genome eleven years ago was the beginning of the individualized medicine revolution, a revolution that cannot happen without digitized personal phenotype information. Eric Topol provides a path forward using your digitized genome, remote sensing devices and social networking to place the educated at the center of medicine.”

J. Craig Venter,Chairman and President, J. Craig Venter Institute

“Eric Topol gives us an eye-opening look at what’s possible in healthcare if people can mobilize to charge the status quo. The Creative Destruction of Medicine is simply remarkable.”

Clayton M.Christensen, Robert and Jane Cizik Professor of Business Administration, Harvard Business School,and author of The Innovator’s Dilemma

“Eric Topol has been a longtime innovator in healthcare. In The Creative Destruction of Medicine, he cites the big waves of innovation that will save healthcare for the future. Real healthcare reform has not yet begun, but it will. The Creative Destruction of Medicine lays out the path.”

Jeffrey Immelt,Chairman and CEO of General Electric

“This is the one book to read for a complete and clear view of our medical future, as enabled by the convergence of digital, mobile,genomic, and life science breakthroughs. Dr. Topol explains how iPhones, cloud computing, gene sequencing, wireless sensors, modernized clinical trials,internet connectivity, advanced diagnostics, targeted therapies and other science will enable the individualization of medicine - and force overdue radical change in how medicine is delivered, regulated, and reimbursed. This book should be read by patients, doctors, scientists, entrepreneurs, insurers,regulators, digital engineers - anyone who wants better health, lower costs, and participation in this revolution.”

Brook Byers,Partner, Kleiner Perkins Caufield & Byers

“Eric Topol is that rare physician willing to challenge the orthodoxies of his guild. He recognizes that in the U.S., health care business-as-usual is unsustainable. But he does not despair. He bears witness to the rise of Homodigitus and the promise it holds to upend the inefficiencies and dysfunction so entrenched in clinical medicine. The Creative Destruction of Medicine is a timely tour de force. It is a necessary heresy.”

Misha Angrist, Assistant Professor, Duke Institute for Genome Sciences & Policy, and author of Here is a Human Being

“Much of the wealth created over the last decades arose out of a brutal transition from ABC’s to digital code. While creating some of the world’s most valuable companies, this process also upended whole industries and even countries. Now medicine, health care, and life sciences are undergoing the same transition. And, again, enormous wealth will be created and destroyed.This book is a road map of what is about to happen.”

Juan Enriquez,Managing Director, Excel Venture Management, and author As the FutureCatches You

Health care is poised to be revolutionized by two forces - technology and consumerism - and Dr. Eric Topol explains why. One-size-fits-all medicine will soon be overtaken by highly personalized,customized solutions that are enabled by breakthroughs in genomics and mobile devices and propelled by empowered consumers looking to live longer, healthier lives. Fasten your seat belts and get ready for the ride—and learn what steps you can take to begin to take control of your health.

Steve Case,co-founder, AOL, and founder of Revolution LLC

“If we keep practicing medicine as we know it today, healthcare will become an unbearable burden. We are in a real race between healthcare innovation and the resistance to change of the medical system. In a comprehensive and well researched tour de force, Eric Topol, always a clear and uncompromising thought leader of his generation, challenges us to imagine the revolutionary potential of a world where medical information no longer belongs to a few and can be automatically collected from the many to greatly improve healthcare for all. This is a must read!”

Elias Zerhouni, MD, President, Global R&D, Sanofi and former director, National Institutes of Health

Dr. Topol believes that medicine, catalyzed by extraordinary innovation that exploits digital information, is about to go through its biggest shakeup in history. His newest book calls for a ‘jailbreak’ from the ideas of the past. In the next phase of medicine, powerful digital tools including mobile sensors and advanced processors will transform our understanding of the individual, enabling creative ‘mash-ups’ of data that will spark entirely new discoveries and spawn ultra-personalized health and fitness solutions. And with over 5.7 billion mobile connections worldwide, the mobile technology platform will have a major impact on that vision - leading to what Dr.Topol describes as nothing less than a ‘reboot’ of the health care system. Qualcomm, and its partners all around the world, are working to bring wireless innovations to market that will contribute to the solution. And we share Dr.Topol’s view that individual consumers have the opportunity, and the power, to increase the pace of the titanic change that’s coming.”

Paul E. Jacobs,PhD, Chairman and CEO, Qualcomm Incorporated

What happens when you combine cellular phone technology with the cellular aberrations in disease? Or create a bridge between the digital revolution with the medical revolution? How will minute biological sensors alter the way we treat lethal illnesses, such as heart attacks or cancer? This marvelous book by Eric Topol, a leading cardiologist, gene hunter and medical thinker, answers not just these questions, but many many more.Topol’s analysis draws us to the very front lines of medicine, and leaves us with a view of a landscape that is both foreign and daunting. He manages to recount this story in simple, lucid language—resulting in an enthralling and important book.”

Siddhartha Mukherjee, author of The Emperor of All Maladies: A Biography of Cancer

“What happens when the super-convergence of smart phones further combines with million-fold lower-cost genomics and diverse wearable sensors? The riveting answer leads to a compelling call to activism—not only for medical care providers, but all patients and everyone looking for the next ‘disruptive’ economic revolution. This future is closer than most of us would have imagined before seeing it laid out so clearly. A must-read.

George Church,Professor of Genetics, Harvard Medical School

“Dr. Topol is the top thought leader in medicine today, with exceptional vision for how its future can be rebooted. This book will create and catalyze a movement for the individualization and democratization of medicine - and undoubtedly promote better health care.”

Greg Lucier, CEO, Life Technologies

“Eric Topol is the perfect author for this book.He has a unique understanding of both genomics and wireless medicine and has a remarkable track record as a charismatic pioneer, visionary, and change agent in medicine. I’m sure this book will reach a very large number of people with information that can both empower and help transform their lives for the better.”

Dean Ornish, M.D., Founder and President, Preventive Medicine Research Institute, and author of The Spectrum

“Dr. Eric Topol is an extraordinary doctor. He’s started a leading medical school, identified the first genes to underlie development of heart disease, led major medical centers, and been a pioneer of wireless medicine. But he is also a remarkable communicator - one of the few top-flight scientists in medicine to be able to genuinely connect with the public. He was, for example, the first physician researcher to question the safety of Vioxx - and unlike most who raise safety questions, actually succeed in bringing the concerns to public attention. I have known and admired Dr. Topol for a long time. I recommend him highly.”

AtulGawande, M.D., author of The Checklist Manifesto

“Eric Topol is uniquely positioned to write such a timely and important book. He leads two institutions - one in genomics and one in wireless health - that will each play a huge role in transforming medicine in the twenty-first century. From this vantage point, he can see unifying themes that will underlie the coming revolution in population and personal health, and he communicates his vision with vibrant energy. Everyone will want to read this book.”

James Fowler,Professor of Medical Genetics and Political Science, UC San Diego, and author of Connected

[Dr. Eric Topol says in his book that "the train has already left the station". Indeed, this column cited on Oct. 15, 2007 "The Year of Miracles" Newsweek article by Prof. Lee Silver . As the column's remarks observed, however, in five years ago (2007), precisely since the article foreshadowed a "Creative Destruction of Medicine", the artilce "Annus Mirabilis" by Prof. Lee Silver was published in all Editions of Newsweek - EXCEPT in the US-Canadian Edition (where there wasn't a single word about it). This colum cited the paper from the European Edition...

The Year of Miracles (Annus Mirabilis) by Lee Silver (full paper)

Likewise, the establishment did not take it very well that Genomics became Informatics (in 2002 Leroy Hood framed Genome Informatics in terms of Systems Biology, while Andras Pellionisz defined it as a Fractal System; FractoGene 2002). Particularly crass detractors came to the fore when Pellionisz published the peer-reviewed science paper "The Principle of Recursive Genome Function" (popularized by the Google Tech Talk YouTube in the same year of 2008), and subsequent YouTube-s on Personal Genome Computing and Personalized Genome Assistant mobiles (for an age when e.g. in India many more people carry smart phones than the number with access to a sewage system):

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A scalable global business model and a (sub)continent offers support of Pellionisz' Fractal Approach: Ten slides winning over a (sub)continent for funding Pellionisz' Fractal Approach

Dr. Andras Pellionisz was a Guest of Honor as well as Keynote Speaker at the ICSCI-2012 "International Conference on Systemics, Cybernetics and Informatics" in Hyderabad, Andhra-Pradesh (February 15-18, 2012, organized by Prof. E.G. Rajan), and subsequently at the ICETT-2012 "International Conference on Emerging Technology Trends on Advanced Engineering Research" in Kollam, Kerala (February 20-21), organized by Prof. B. Kumar. His biophysics-approach, using tensor- and fractal geometry to unify genomics and neuroscience was awarded at both international congresses. In the third state of Karnataka, in Bangalore, he conducted discussions in addition to Academia with Private sector, and Government officials. As also reflected by a visit a few weeks earlier by Dr. Francis Collins NIH Director (see below in this column), India flexes muscles to answer the challenge that the genome informatics initiatives of China (BGI) and Korea (Samsung) represent.

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