Harvard Biophysics 101 (MIT-OCW Health Sciences & Technology 508)MIT-OCW Health Sciences & Technology AM Thu 8-Feb 2007 Barker CenterBarker Center, Room Quincy St.Room 316 Genomics, Computing, Economics

Class outline (1) Topic priorities for homework since last class (2) Quantitative exercise (3) Project level presentation & discussion (4) Sub-project reports & discussion (5) Discuss communication/presentation tools (6) Topic priorities for homework for next class

Binomial, Poisson, Normal

p and q  p  q  q = 1 – p two types of object or event. Factorials 0! = 1 n! = n(n-1)! Combinatorics (C= # subsets of size X are possible from a set of total size of n) n! X!(n-X)!  C(n,X) B(X) = C(n, X) p X q n-X  np  2  npq (p+q) n =  B(X) = 1 Binomial frequency distribution as a function of X  {int  n} B(X: 350, n: 700, p: 0.1) = × = PDF[ BinomialDistribution[700, 0.1], 350] Mathematica ~= 0.00 = BINOMDIST(350,700,0.1,0) Excel

Quantitative definition of life (& utility of such) "papers incubating where we do calculate the statistical complexity of various real-world processes" James P. Crutchfield and Karl Young, "Inferring Statistical Complexity," Physical Review Letters 63 (1989)

Bits & complexity How many bits to represent your genome (from your mother)? How many additional bits for paternal DNA? How many bits to define the ribosome structure below?

3 Exponential technologies (synergistic) Shendure J, Mitra R, Varma C, Church GM, 2004 Nature Reviews of Genetics. Carlson 2003 ; Kurzweil 2002; Moore 1965 urea E.coli B12 tRNA operons telegraph Computation & Communication (bits/sec) Synthesis (daltons) Analysis (bp/$) tRNA

Vertebrate brain size evolution Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiensOngoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens Science 2005 Bond et al 2002 ASPM is a major determinant of cerebral cortical size. Nat Genet. 32(2): Jerison, Paleoneurology & the Evolution of Mind, Scientific Amer Human-chimp 1.2% Human-human 0.1% Genome: 2x 3Gbp

Brain complexity “The retina's 10 million detections per second [.02 g]... extrapolation instructions per second to emulate the 1,500 gram human brain.... thirty more years..” (Morovec99)(Morovec99) fig Edge & motion detection (examples)examples Discovering the Capacity of Human MemoryDiscovering the Capacity of Human Memory Wang 2003 N=10 11 neurons, m=1000 connections: n!/[m!(n-m)!] = 10^8432 bits. How Many Bytes in Human MemoryHow Many Bytes in Human Memory? Merkle 1988 Landauer 2 bits/sec (<10^8 bits per lifetime)

Inheritance is not just DNA

Past Locomotion50 Ocean depth75m Visible.4-.7  Temperature Memory years20 Memory bits10 9 Cell therapy Current km/h 10,912 m pm-Mm o K most tissues

Class outline (1) Topic priorities for homework since last class (2) Quantitative exercises: psycho-statistics, combinatorials, random/compression, exponential/logistic, bits, association & multi- hypotheses (3) Project level presentation & discussion (4) Sub-project reports & discussion: Personalized Medicine & Energy Metabolism (5) Discuss communication/presentation tools (6) Topic priorities for homework for next class

Common Disease – Common Variant Theory. How common? ApoE allele  4 : Alzheimer’s dementia, & hypercholesterolemia 20% in humans, >97% in chimps>97% in chimps HbS 17% & G6PD 40% in a Saudi sample CCR5  32 : resistance to HIV 9% in caucasians

THE FUTURE OF HUMAN NATURE The Singularity Is Near : When Humans Transcend Biology The Law of Accelerating Returns by Ray Kurzweil An analysis of the history of technology shows that technological change is exponential, contrary to the common-sense "intuitive linear" view. So we won't experience 100 years of progress in the 21st century -- it will be more like 20,000 years of progress (at today's rate)... ultra-high levels of intelligence that expand outward in the universe at the speed of light. Bill Joy Wired 8.04 | Apr 2000 Our most powerful 21st-century technologies - robotics, genetic engineering, and nanotech - are threatening to make humans an endangered species.

Haplotype Diversity across 100 Candidate Genes for Inflammation, Lipid Metabolism, and Blood Pressure Regulation in Two Populations. Crawford, et al.Crawford, et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration Hageman, et al. 2005Hageman, et al. Personalized Medicine/Genetics

Common Disease – Common Variant Theory. How common? ApoE allele  4 : Alzheimer’s dementia, & hypercholesterolemia 20% in humans, >97% in chimps>97% in chimps HbS 17% & G6PD 40% in a Saudi sample CCR5  32 : resistance to HIV 9% in caucasians

SNPs & Covariance in proteins e4 20% ApoE e3 80% Ancestral = Arg 112 Thr 61

Humans consume 2kW per person = kW. Sunlight hits the earth at 40,000 times that rate (70% ocean). CO 2 /yr: Fossil fuel use releases 5 Gton. Ocean & terrestrial productivity = ~100 Gton each. Autotrophs: Prochlorococcus cells globally (10 8 per liter) Sequestration v. respiration v. use: heterotrophs (Pelagibacter), phages, predators (Maxillopoda, Malacostraca, herring) Energy & CO 2 Sequestration Morris et al. Nature 2002 Dec 19-26;420(6917):  0.1 mm 6 cm Lab:100X

Class outline (1) Topic priorities for homework since last class (2) Quantitative exercise (3) Project level presentation & discussion (4) Sub-project reports & discussion (5) Discuss communication/presentation tools (6) Topic priorities, homework for next class

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