Computers and Programming for Biologists

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Computers and Programmingfor Biologists
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What is Bioinformatics?

• The use of information technology to collect,
  analyze, and interpret biological data.
• An ad hoc collection of computing tools that are
  used by molecular biologists to manage research
  data.
• Computational algorithms
• Database schema
• Statistical methods
• Data visualization tools

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The Human Genome Project
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A Genome Revolution in Biology and Medicine

• We are in the midst of a "Golden Era" of biology
• The Human Genome Project has produced a huge
  storehouse of data that will be used to change
  every aspect of biological research and medicine
• The revolution is about treating biology as an
  information science, not about specific
  biochemical technologies.

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The job of the biologist is changing
As more biological information becomes available
and laboratory equipment becomes more automated
...

• The biologist will spend more time using
  computers
• on experimental design and data analysis (and
  less time doing tedious lab biochemistry)
• Biology will become a more quantitative science
  (think how the periodic table affected chemistry)

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What are the Tools?

• Alignment
• Similarity string matching
• Pattern search
• Hash tables and substitution matrices
• Clustering
• Genome assembly and annotation

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Align by hand

• GATGCCATAGAGCTGTAGTCGTACCCT lt
• gt CTAGAGAGC-GTAGTCAGAGTGTCTTTGAGTTCC

Somebody should make a computer program for this
kind of thing
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Global vs. Local Alignments
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BLAST Algorithm
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gtZFISH9GNL-TI fi72b02.y1 Length
724 Score 307 bits (786), Expect 8e-82
Identities 145/200 (72), Positives 166/200
(82), Gaps 1/200 (0) Frame 3 Query 45
VLLKEYRVILPVSVDEYQVGQLYSVAEASKNXXXXXXXXXXXXXXPYEK-
DGEKGQYTHK 103 LKERLPVSVEYQVGQLYS
VAEASKN PYEK DGEKGQYTHK Sbjct 123
MLIKEFRIVLPVSVEEYQVGQLYSVAEASKNETGGGDGVEVLKNEPYEKE
DGEKGQYTHK 302 Query 104 IYHLQSKVPTFVRMLAPEGALNI
HEKAWNAYPYCRTVITNEYMKEDFLIKIETWHKPDLG 163
IY LQSKVPFVRLAP AL IHEKAWNAYPYCRTVTNEYMKF
LI IETWHKPDLG Sbjct 303 IYRLQSKVPSFVRLLAPSSALIIHE
KAWNAYPYCRTVLTNEYMKDNFLIMIETWHKPDLG 482 Query
164 TQENVHKLEPEAWKHVEAVYIDIADRSQVLSKDYKAEEDPAKFKSI
KTGRGPLGPNWKQE 223 QENVH L E WK VE
IDIADRSQV KDYK EDPA FKS KTGRGPLGPWKE Sbjct
483 EQENVHNLDSERWKQVEVIHIDIADRSQVDTKDYKPDEDPATFKSQ
KTGRGPLGPDWKKE 662 Query 224 LVNQKDCPYMCAYKLVTVK
F 243 L DCPMCAYK VTV F Sbjct 663
LPQKRDCPHMCAYKXVTVNF 722
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Clustering (Phylogenetics)
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Genome Assembly
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Raw Genome Data
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UCSC
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The Challenge of New Data Types

• Gene expression microarrays
• thousands of genes, imprecise measurements
• huge images, private file formats
• Proteomics
• high-throughput Mass Spec
• protein chips protein-protein interactions
• Genotyping
• thousands of alleles, thousands of individuals

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cDNA spotted microarrays
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High-Throughput Genotyping
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BioinformaticsBeyond Using Websites

• You can do a lot of sophisticated bioinformatics
  using public websites
• But at some point you may be faced with a LOT of
  data - thousands of searches, annotations, etc.
• The only solution is to have your own
  bioinformatics computer, database, and custom
  programs.
• Needs more processor power and more hard drive
  space than a typical desktop personal computer

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Bioinformatics Requires Powerful Computers

• One definition of bioinformatics is "the use of
  computers to analyze biological problems.
• As biological data sets have grown larger and
  biological problems have become more complex, the
  requirements for computing power have also grown.
• Computers that can provide this power generally
  use the Unix operating system - so you must learn
  Unix be a computational biologist

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Stable and Efficient

• Unix is very stable - computers running Unix
  almost never crash
• Unix is very efficient
• it gets maximum number crunching power out of
  your processor (and multiple processors)
• it can smoothly manage extremely huge amounts of
  data
• it can give a new life to otherwise obsolete Macs
  and PCs
• Most new bioinformatics software is created for
  Unix - its easy for the programmers

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Open Source Bioinformatics

• Almost all of the bioinformatics software that
  you need to do complex analyses is free for UNIX
  computers
• The Open Source software ethic is very strong
  among biologists
• Bioinformatics.org
• Bioperl.org
• Open-bio.org
• New algorithms generally appear first as free
  software (a publication requirement)

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Free Software

• Linux operating system, mySYQL database
• Perl - programming language
• Blast and Fasta - similarity search
• Clustal - multiple alignment
• Phylip - phylogenetics
• Phred/Phrap/Consed - sequence assembly and SNP
  detection
• EMBOSS - a complete sequence analysis package
  created by the EMBL (like GCG)

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Computer Hardware is not Free

• However, you can build a powerful Linux cluster
  for 20-50K (depending on how much power you
  need)
• The real cost is for a person to manage the
  machines, install the software, and train
  scientists to use it.
• Small schools can join together or affiliate with
  a larger neighbor.

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Do Biologists have to become Programmers?

• No, but it can give you a big advantage.
• More and more of biology is becoming computer
  aided design of experiments, automated equipment,
  and computational analysis of the results.
• I just want to say one word to you ...
  Databases

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Why teach bioinformatics in undergraduate
education?

• Demand for trained graduates from the biomedical
  industry
• Bioinformatics is essential to understand current
  developments in all fields of biology
• We need to educate an entire new generation of
  scientists, health care workers, etc.
• Use bioinformatics to enhance the teaching of
  other subjects genetics, evolution, biochemistry

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Genomics in Medical Education

• The explosion of information about the new
  genetics will create a huge problem in health
  education. Most physicians in practice have had
  not a single hour of education in genetics and
  are going to be severely challenged to pick up
  this new technology and run with it."
• Francis Collins

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Becoming a Unix Power User

• Learn more Unix commands
• Use the shell to execute simple programs
• Write scripts - automate repetitive tasks
• Download and install the latest bioinformatics
  software
• Drive your system manager crazy or get your own
  Unix machine
• (Linux on an Intel machine or Mac OS-X)

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BioPerl

• Why re-invent the wheel?
• Lots of common bioinformatics tasks have already
  been programmed as modules in Perl.
• Grab sequences from GenBank, extract e-values and
  annotation from Blast results, etc.
• Download from www.bioperl.org

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Resources

• Notes for Lincoln Steins course on
• Genome Informatics
• http//stein.cshl.org/genome_informatics/index.htm
  l
• BioPerl.org http//bio.perl.org/
• PERL for biologists (Kurt Stüber)
• http//caliban.mpiz-koeln.mpg.de/stueber/perl/
• Why Biologists Want to Program Computers
• by James Tisdall http//www.oreilly.com/news/perl
  bio_1001.html

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Resources for Bio-Computing
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Stuart M. Brown, Ph.D.stuart.brown_at_med.nyu.eduww
w.med.nyu/rcr
Bioinformatics A Biologist's Guide to
Biocomputing and the Internet
Essentials of Medical Genomics
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