GENOME ANALYTICS SOFTWAREENABLING FRACTAL APPROACH TO A GLOBAL

GENOME ANALYTICS SOFTWARE-ENABLING FRACTAL APPROACH TO A GLOBAL, GENOME-BASED ECONOMY, WITH PERSONALIZED HEALTH-CARE SYSTEMS Featuring the DNA / RNA System as a Fractal Genomic Cerebellum Andras J. Pellionisz Ph. D. in Computer Engineering, Ph. D. in Biology, Ph. D. in Physics bio President of Hol. Gen. Tech, Inc. Silicon Valley, California company February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

Genomics is Informatics, 2002 System Theory ? Fractal System ! Fracto. Gene, 2002 Unification of Neuroscience and Genomics, 2012 February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

2 0 0 , 2 e n e G to c a r F z s i n o i ll e P – em t s y S l ta c a r F a e: m o n e o. G l Ho February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

Public Domain Fractal Rendering of Heart Coronaries, Lung Fracto. Gene; seed-concept of recursion in Pellionisz 1989, USPTO priority Date Aug. 1 st, 2002), 2005, 2008, Cold Spring Harbor, 2009, Springer Verlag 2012 February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

All Genomes are Fractal? The Indian DNA Certainly is… February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

3 D Hilbert-curve (“fractals” go back to Euler!) is a) Ultra dense (fold 2 m DNA into 6 micron nucleus) b) Knot-free (for unhindered “pervasive transcription”) c) “See through” (for maximal functional closeness of linearly remote fragmented genomic regions) Dr. Eric Schadt, CSO, Pacific Bio. Sciences: “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 structures 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 February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

Independent Experimental Proof of Concept: Fractal Defect Causes Cancer Link High order chromatin architecture shapes the landscape of chromosomal alterations in cancer Geoff Fudenberg, Gad Getz, Matthew Meyerson & Leonid A Mirny Nature Biotechnology 29, 1109– 1113 (2011) doi: 10. 1038/nbt. 2049 Abstract. The accumulation of data on structural variation in cancer genomes provides an opportunity to better understand the mechanisms of genomic alterations and the forces of selection that act upon these alterations in cancer. Here we test evidence supporting the influence of two major forces, spatial chromosome structure and purifying (or negative) selection, on the landscape of somatic copynumber alterations (SCNAs) in cancer. Using a maximum likelihood approach, we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (Hi. C) and described by the proposed fractalglobule model. This analysis suggests that the distribution of chromosomal alterations in cancer is spatially related to threedimensional genomic architecture and that purifying selection, as well as positive selection, influences SCNAs during somatic evolution of cancer cells. February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

High order chromatin architecture shapes the landscape of chromosomal alterations in cancer Geoff Fudenberg, Gad Getz, Matthew Meyerson & Leonid A Mirny Nature Biotechnology 29, 1109– 1113 (2011) February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

Intact Fractality: The Ultra-Dense Genome is Functionally Transparent; Readable in Parallel Fractal Defect (of a Copy Number Alteration Here) Clogs Transparency; Disrupts “Functional Proximity”; the Result is Misregulation (Cancer) February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.

February 15, 2012 Andras J. Pellionisz International Conference on Systemics; Cybernetics and Informatics (ICSCI-2012) Hyderabad, India, by Pentagram Res. Ctr.