Biotechnology and Computing

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Biotechnology and Computing

• BIF 101 Fall 2007
• Debra T. Burhans, Ph.D.
• Canisius College
• burhansd_at_canisius.edu

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What is Biotechnology?

• A general definition of biotechnology is the use
  of biology or biological processes to develop
  helpful products and services. In this sense,
  humans have been using biotechnology (biology to
  create products) for centuries, for example in
  the breeding of farm animals for offspring with
  desirable traits and the use of yeast to make
  bread, beer, and wine. A modern definition of
  biotechnology is the set of biological techniques
  originally resulting from basic research,
  specifically molecular biology and genetic
  engineering, and now used for research and
  product development. Alternatively, biotechnology
  can be defined as the scientific manipulation of
  organisms at the molecular genetic level to make
  beneficial products.
• http//www.csrees.usda.gov/nea/biotech/biotech
  _all.html

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Biotechnology

• Research to develop new technologies
• Includes the application of information developed
  by that research to the development of commercial
  products
• Includes all of the business activity that is
  required to bring these products to market
• Applied in fields from agriculture to aerospace
  engineering

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Bio-technology

• Many high-throughput techniques have been
  developed that enable biologists to generate
  tens, even hundreds of thousands of data points
  with a single experiment
• Some examples include cloning, PCR, sequencing
  and microarrays

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Molecular Biology Tools
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Restriction Enzymes

• Molecular scissors
• Create blunt or sticky ends
• Used singly or in combinations to cleave DNA
  sequences

The
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Gel Electrophoresis
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Blotting
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Hybridization

• Labeled fragment of DNA (probe) is allowed to
  base pair with sample
• Sample DNA may be immobilized on a membrane or
  may be contained in wells
• Microarrays are small chips containing thousands
  of samples that are frequently used in todays
  biology laboratories

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Expression Data

• The context (e.g. tissue type, stage of growth of
  an organism, etc) of a cell determined its
  pattern of gene and protein expression
• Expression patterns are measured using
  microarrays
• Each spot on a microarray attracts and binds
  particular sequences
• The amount of sequence bound to a spot can be
  quantified
• Initially gene expression arrays, now there are
  protein expression arrays
• Genome on a chip, can have tens of thousands of
  spots on one chip

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Affymetrix Oligonucleotide Chip
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Microarray Data
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cDNA spotted Microarray Chip
Atlantic salmon cDNA microarray
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Microarray Data
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Microarray Data in Spreadsheet

• Spreadsheet file

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Cloning

• General strategy use a biological machine to
  do the work
• Isolate the piece of sequence you want to copy
• Insert the sequence into a molecule that can
  replicate itself
• Insert that molecule into (often) a bacterium
  that multiplies quickly
• Each new generation of bacteria contains copies
  of your DNA

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Making Copies - cloning
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The Polymerase Chain Reaction
The reaction is placed in an automated thermal
cycler. Reactions typically have three steps -
denaturation to separate the DNA strands -
approximately 95oC - annealing to permit
primers to bind to target - approximately
60oC - actual temperature depends on
composition of primers - polymerization to
permit the enzyme to copy the template -
approximately 72oC This is repeated 30 or more
times.
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Making copies - PCR
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Sequencing present and future

• Not so long ago it took a year to sequence a few
  hundred bases, now an entire genome can be
  sequenced in a day
• The newest technologies will enable sequencing of
  genomes of individuals leading the way towards
  personalized medicine
• The ability to easily amplify a DNA sequence
  using PCR, creating millions of copies, has led
  to the use of DNA evidence in crime fighting
• The more genomes we sequence the more we learn
  about how different organisms are related
• The generation of sequence data has far outpaced
  our ability to analyze the data (at this point in
  time)
• Data is immediately recorded in a computer and
  can be displayed as an electropherogram

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DNA Sequencing
Modern DNA sequencing is done with an automated
sequencer. DNA sequencers use new
technologies -fluorescent tags for each
base -permit machine basecalling -dideoxy
chain termination chemistry -efficient and
amenable to automation -capillary
electrophoresis -permits analysis of small
samples -direct output to computer -minimizes
errors and speeds process
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Sequencing figuring out what the letters
aredideoxy chain termination
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Sequencing

• Sequences are passed through a capillary
  electrophoresis apparatus that arranges them by
  length
• The result is that one labeled nucleotide at a
  time passes through the capillary tube
• Labeled nucleotides are excited by a laser and
  emit a light signal corresponding to A, C, G, or T

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Electropherogram
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Sequencing Facility Whitehead Institute
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Pyro Sequencing

• This newest of technologies is the latest
  standard in sequences
• As bases are incorporated they emit light
  signals, allowing a single reconstruction of an
  original sequence to yield all of its letters
• http//www.personalchemistry.com/DynPage.aspx?id8
  726mn11366

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Sequencing tied to physical maps

• HGP (Human Genome Project)
• Sequencing video

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Shotgun approach
DNA sequence is obtained through a shotgun
approach -DNA is fragmented by shooting it out
of a small opening, e.g. the end of a
syringe -fragments are cloned in suitable
bacterial vectors -fragments are sequenced using
primers flanking fragment in plasmid - sequence
of fragments must be reassembled which relies on
the existence of very fast, large computing
resources - there are no physical maps to help
with reassembly
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Computing
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B.C.

• Around 1600 BC the abacus, the first mechanical
  calculating device, was created by the Chinese
  (image http//www.johnnapier.com/abacus.htm)
• 300-400 BC Aristotle invented syllogistic
  logic, the first formal deductive reasoning
  system
• A, A ? B (modus ponens)
• B

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Early A.D.

• 780-850 Algorithm Idea invented by Mohammed
  ibn-Musa al-Khwarizmi, who was part of the royal
  court in Baghdad.
• The notion of an algorithm is fundamental to
  computing. An algorithm is a step by step
  procedure for solving a problem that is
  guaranteed to find the right answer after a
  finite number of steps.
• 13th century Ramom Llull, a Spanish theologian,
  invented a machine (Ars Magna) for discovering
  nonmathematical truths through eccentric logic
  (he wanted to prove the truth of the bible)
• 1434 self striking water clock
• 15th century Gutenberg and the printing press

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1500s

• 1500 Leonardo DaVincis mechanical calculator
  (designed, has since been built and works).
  DaVinci also designed a mechanical knight
• Early 1500s Hans Bullmann creates the first
  androids simulated people that play musical
  instruments
• Clock makers create mechanical animals
• 1533 Johann Muller, aka Regiomontanus, created an
  iron fly and an iron eagle both of which were
  purported to fly
• 1580 Rabbi Loew of Prague invented the Golem, a
  clay figure that could be brought to life

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1600s

• Descartes proposed that bodies of animal were
  nothing more than complex machines
• Hobbes published The Leviathan, describing a
  material and combinatorial theory of thinking
• Early 1600s Napier created Napiers bones, carved
  wooden strips for mechanically computing
  logarithms
• 1621 Oughtred invented the slide rule based on
  what Napier had done
• 1642 Pascal created the first mechanical digital
  calculating machine
• 1673 Leibniz invented the multiplier

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1800s - I

• 1801 Jacquard invents a loom where the pattern
  is controlled using punched cards made out of
  wood (http//en.wikipedia.org/wiki/Jacquard_loom)
• 1811-1816 Ned Ludd leads the Luddite movement to
  destroy machinery (England)
• 1822 Charles Babbage designed the Difference
  Engine using Newtons method of differences it
  could approximate the value of a given polynomial
  using only subtraction (http//en.wikipedia.org/wi
  ki/Difference_engine)

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1800s - II

• Ada Byron (Lady Lovelace) worked with Babbage on
  his designs and is considered to be the first
  computer programmer
• 1833 Babbage designs the Analytical Engine,
  considered to be the first programmable computer
  it was never built
• The analytical engine was to be powered by a
  steam engine and would have been over 30 meters
  long and 10 meters wide. The input (programs and
  data) was to be provided to the machine via punch
  cards, a method being used at the time to direct
  mechanical looms. For output, the machine would
  have a printer, a curve plotter and a bell. The
  machine would also be able to punch numbers onto
  cards to be read in later. It employed ordinary
  base-10 fixed-point arithmetic. There was a store
  (i.e., a memory) capable of holding 1,000 numbers
  of 50 digits each. An arithmetical unit (the
  "mill") would be able to perform all four
  arithmetical operations.
• The programming language to be employed was akin
  to modern day assembly languages. Loops and
  conditional branching were possible and so the
  language as conceived would have been
  Turing-complete long before Alan Turing's
  concept. Three different types of punch cards
  were used one for arithmetical operations, one
  for numerical constants, and one for load and
  store operations, transferring numbers from the
  store to the arithmetical unit or back. There
  were three separate readers for the three types
  of cards. (From Wikipedia, http//en.wikipedia.org
  /wiki/Analytical_engine)

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1800s - III

• 1847 George Boole developed a binary logic that
  could be used to represent (some) laws of
  thought
• 1887 Hollerith developed the modern-day punched
  card to tabulate the US Census, he went on to
  found a company that ultimately became IBM

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20th Century

• 1910-1913 Russell and Whiteheads Principia
  Mathematica leads philosophy into the logical
  analysis of knowledge
• 1936 Alan Turing published his paper On
  Computable Numbers which describes the concept of
  a Turing Machine
• 1943 The term cybernetics is coined in a paper
• 1943 McCulloch and Pitts do pioneering work on
  neural networks
• 1950 Alan Turing proposed the Turing Test to
  determine machine intelligence

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Turing Test

• The Turing Test is considered by some to be the
  gold standard for determining whether a machine
  is intelligent
• Many, however, regard it as an unsatisfactory way
  to define intelligence
• Turing predicated that by the year 2000 a general
  machine intelligence would pass the test
• Ray Kurzweil believes this will happen by 2020
• The Loebner competition is a limited version of
  the TT
• Image http//www-user.tu-chemnitz.de/rima/PsyLin
  /hausarbeit/img8.png

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First generation electronic computers1937 - 1953

• vacuum tubes punched cards or magnetic tape
  machine language magnetic core memory
• 1941 Atanasoff and Berry (Iowa State) build the
  ABC which could solve partial differential
  equations with many unknowns, it was not,
  however, programmable
• 1943 Turing Colossus used by British military
  to crack the German code in WWII
• 1945 ENIAC first general purpose programmable
  computer (Eckert, Mauchly, vonNeumann)
• 1945 first computer bug, discovered by Grace
  Hopper
• 1948 transistor invented
• 1955 EDVAC stored program concept, program and
  data can both be stored
• 1950s IBM mainframe computers

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More Generations of Computing Machines

• Second generation electronic computersmid 50s
  mid 60s
• transistors punched cards or magnetic tape
  assembly language and some high level languages
  magnetic core memory
• Third generation computers mid 60s early 70s
• integrated circuits silicon chips punched
  cards, magnetic tape, magnetic disks magnetic
  core, some semiconductor memory e.g. IBM
  System/360
• 1968 microprocessor invented
• Fourth generation computers 1972 1984
• VLSI (very large scale integration)
  microprocessor chip magnetic disks, floppy
  disks high level languages user-friendly
  software semiconductor memory
• 1976 Apple II
• 1981 IBM PC

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Computing Revolution

• Computers have been steadily and precipitously
  decreasing in price and increasing in power and
  storage space
• Moores Law number of transistors on chips
  doubles every two years
• Update of Moores law data density on chips
  doubles every 18 months
• Computer science researchers continue to find new
  ways of solving problems

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Programming

• A program is a set of instructions a computer can
  follow
• There are many different programming languages
• Machine language (binary)
• Assembly language (primitive instructions, e.g.
  ADD)
• High Level language (Java, Fortran, Perl, etc.)
• Programs are what make computers behave in a
  certain manner
• Algorithms can be realized as programs

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Limits to computation

• P polynomial time
• NP non-deterministic polynomial time
• Problems whose solutions involve NP algorithms
  are effectively not computable
• There are problems for which no computer can find
  a solution
• This is related to a mapping between algorithms
  (computer programs) and the integers
• There are more real numbers than integers,
  therefore there are noncomputable numbers (i.e.
  problems)
• Until a fundamental change in the design of
  computers happens this will continue to be the
  case (possibly quantum computing)

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Computer System Components(Von Neumann
architecture)
PROCESSOR
OUTPUT
INPUT
MEMORY