Introduction to Computational Biosciences and Bioinformatics

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Introduction to Computational Biosciences and
Bioinformatics

• Alex Ropelewski
• ropelews_at_psc.edu
• Pittsburgh Supercomputing Center
• National Resource for Biomedical Supercomputing
• http//staff.psc.edu/ropelews/jsu/Begin_CS_Jackson
  _State_Intro_Computational_BioScience.ppt
• http//compbio.jsums.edu/awareness/week1.html

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Computational Biosciences

• The application of
• computer science, engineering,
• physical science and mathematics
• to the way in which plants, animals and humans
  function

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Computational Bioscience Fields

• Bioinformatics
• Structural biology
• Genetic databases
• Quantitative ecology
• Physiological modeling
• Medical informatics
• Image processing and visualization

• Medical imaging
• Biomedical instrumentation
• Biomathematics
• Neuroscience
• Telemedicine
• Biomedical engineering
• Other related areas

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Bioinformatics

• The interdisciplinary science of using
  computational approaches to analyze, classify,
  collect, represent and store biological data with
  the goal of accelerating and enhancing the
  understanding of DNA, RNA and Protein sequences.

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Structural Biology
The branch of the sciences concerned with the
molecular structure of biological macromolecules
such as proteins and nucleic acids, how they
acquire the structures they have, and how
alterations in their structures affect their
function.
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Physiological Modeling
The study of the mechanical, physical, and
biochemical functions of living organisms through
the use and creation of mathematical models of
physiological systems. Examples include models of
components of organisms, such as particular
organs or cell systems.
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Image Processing and Visualization
The science of organizing, displaying, and
analyzing image data taken from any living
organism in a realistic life-like manner.
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Computational Neuroscience and Signal Processing
Applying mathematical and computational methods
to understand the signaling, control and other
networks in living organisms
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Who Employs Computational Bioscientists?

• Pharmaceuticals Biotechnology (Bayer,
  Schering-Plough, Amgen, Merck, Eli Lilly, etc,)
• Hospitals (particularly research hospitals)
• Agriculture (Monsanto, Pioneer, etc.)
• Academia (particularly research
  universities/institutes)
• Government
• NIH (many institutes including NLM, NCBI, NCI,
  CDC)
• DOE (National labs)
• Department of Defense (including Army Corps of
  Engineers)
• Agriculture, Veterans Affairs, NSF
• Government Contractors (such as Computercraft,
  SRA)

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Computational Biosciences Job Growth
Engineers, Life and Physical Scientists and
Related Occupations. Occupational Outlook
Handbook, 2008-09 Edition. Department of Labor,
Bureau of Labor Statistics
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Computational Biosciences Salaries
National Occupational Employment and Wage
Estimates Department of Labor, Bureau of Labor
Statistics, May 2007
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Computational Biosciences

• Interdisciplinary skills are required
• Require knowledge in the following areas
• Biology
• Chemistry
• Computer Science
• Mathematics
• Statistics
• Physics
• Engineering

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Computational Biosciences Required Skill Sets

• Agricultural and food scientists need the
  ability to apply statistical techniques, and the
  ability to use computers to analyze data and to
  control biological and chemical processing.
• Biological scientists usually study allied
  disciplines such as mathematics, physics,
  engineering and computer science. Computer
  courses are beneficial for modeling and
  simulating biological processes, operating some
  laboratory equipment and performing research in
  the emerging field of bioinformatics
• Computer skills are essential for prospective
  environmental scientists and hydrologists.
  Students who have some experience with computer
  modeling, data analysis and integration, digital
  mapping, remote sensing and Geographic
  Information Systems will be the most prepared to
  enter the job market
• Medical scientists in addition to required
  courses in chemistry and biology undergraduates
  should study allied disciplines such as
  mathematics, engineering, physics, and computer
  science

Engineers, Life and Physical Scientists and
Related Occupations. Occupational Outlook
Handbook, 2008-09 Edition. Department of Labor,
Bureau of Labor Statistics
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Computational Biosciences Required Skill Sets

• Developments in the field of Chemistry that
  involve life sciences will expand, resulting in
  more interaction among biologists, engineers,
  computer specialists and chemist. Chemistry
  majors usually study biological sciences
  mathematics physics and increasingly computer
  science. Computer courses are essential because
  employers prefer job applicants who are able to
  apply computer skills to modeling and simulation
  tasks and operate computerized laboratory
  equipment. This is increasingly important as
  combinatorial chemistry and advanced screening
  techniques are more widely applied. Courses in
  statistics are useful because chemists need the
  ability to apply basic statistical techniques.
  Chemists should experience employment growth in
  pharmaceutical and biotechnology research as
  recent advances in genetics open new avenues of
  treatment for diseases. Job growth for chemists
  is expected to be strongest in pharmaceutical and
  biotechnology firms.

Engineers, Life and Physical Scientists and
Related Occupations. Occupational Outlook
Handbook, 2008-09 Edition. Department of Labor,
Bureau of Labor Statistics
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Bioinformatics

• The interdisciplinary science of using
  computational approaches to analyze, classify,
  collect, represent and store biological data with
  the goal of accelerating and enhancing the
  understanding of DNA, RNA and Protein sequences.

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What is a Sequence?

• A sequence is a way to represent a protein, DNA,
  or RNA molecule as a character string.

Phospholipase A2 - Bos taurus (Bovine).
MRLLVLAALLTVGAGQAGLNSRALWQFNGMIKCKIPSSEPLLDFNNYGCY
CGLGGSGTPV DDLDRCCQTHDNCYKQAKKLDSCKVLVDNPYTNNYSYSC
SNNEITCSSENNACEAFICNC DRNAAICFSKVPYNKEHKNLDKKNC
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Molecular Alphabet

• DNA/RNA Sequences Letters represent side chains
  or bases
• A - Adenine
• C - Cytosine
• G - Guanine
• T - Thymine (DNA)
• U - Uracil (RNA)
• X or N (Unknown)

Image from Wikipedia Commons http//en.wikipedia.
org/wiki/FileDNA_chemical_structure.svg
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Molecular Alphabet

• Protein Sequences Letters represent amino
  acids

• A - Alanine
• R - Arginine
• N - Asparagine
• D - Aspartic acid
• C - Cysteine
• E - Glutamic acid
• Q - Glutamine
• G - Glycine
• H - Histidine
• I - Isoleucine
• L - Leucine
• K Lysine
• M Methionine
• F - Phenylalanine
• P - Proline
• S - Serine
• T - Threonine
• W - Tryptophan
• Y - Tyrosine

N
Q
P
G
I
C
L
C
Y
Image from Wikipedia Commons http//en.wikipedia.
org/wiki/FileOxytocin.jpg
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What is an Information Library?

• A compilation of prior experimental knowledge
  about biologically relevant molecules into a
  computer system.
• Bioinformatics power is in the ability to
  leverage and apply this prior experimental
  knowledge to additional biological problems.
• In order to effectively search prior experimental
  knowledge, the prior experimental knowledge must
  be organized in a way that makes sense from both
  a computer science prospective and a biological
  point of view.

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How is Information Organized?

• From a computer-science perspective, there are
  several ways that data can be organized and
  stored
• In a relational database
• In a flat file
• In a networked (hyperlinked) model
• From a biologists perspective, there are also
  several different ways that data can be organized

• Sequence
• Structure
• Family/Domain
• Species
• Taxonomy

• Function/Pathway
• Disease/Variation
• Publication Journal
• And many other ways

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Representing Biological Data

• Sequence Libraries
• Character based
• Classification Libraries (Aligned sets of
  sequences)
• Ambiguous consensus patterns
• Weight Matrix
• Position Specific Scoring Matrix (Profile)
• Hidden Markov Models
• Structural Libraries
• X,Y,Z coordinates for each alpha carbon atom
• Taxonomy
• Tree structure represents the taxonomic lineage

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What does a biologist do with this data?

• Search for similar sequences (sequences that
  share a biological relationship)

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What does a biologist do with this data?

• Search for similar sequences (sequences that
  share a biological relationship)

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What does a biologist do with this data?

• Align groups of sequences that share a biological
  relationship (family)

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What does a biologist do with this data?

• Understand phylogenetic relationships of the
  family.

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What does a biologist do with this data?

• Understand key positions (residues) of the family.

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What does a biologist do with this data?

• Understand how key positions affect the structure
  and function of the molecule being studied

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What does a biologist do with this data?

• Use structural data for a molecule from one
  species to model a related molecule from another
  species.

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Job Opportunities in Bioinformatics

• This course will teach you many essential skills
  that are asked for in these job postings.
• Lets look at actual job postings asking for
  bioinformatics expertise
• Not all jobs will be labeled bioinformatics or
  sequence analysis many are in a related
  computational bioscience field.
• Specific skills required

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Summer Internship-Computational Biology

• QualificationsTo be eligible for a
  Computational Biology Summer Scientific
  Internship students will have completed their
  undergraduate Sophomore year (by June 2009)
• Be majoring in a biological, chemistry or
  computer science program.
• Candidates would have completed at least one
  programming course before the start of the
  internship.
• All interns must have current authorization to
  work for any employer within the United States.
• Experience with MatLab, SQL, C and/or PERL
  experience is desired.

http//jobview.monster.com/getjob.aspx?JobID78206
043JobTitleSummerInternship-ComputationalBiolo
gyqcomputationalbiologycyuslid316re0pg1
dv1AVSDM2008-12-18143a203a00seq2fseo1i
sjs1re1000
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Bioinformatics Assembly Analyst

• Responsibilities
• assembling genome sequence data using a variety
  of tools and parameters and performing the
  experiments needed to evaluate sequencing
  strategies
• using existing software and databases to analyze
  genomic data and correlating assemblies and
  sequences with a variety of genetic and physical
  maps and other biological information
• identifying problems and serving as point of
  contact for various groups to propose and
  implement solutions
• proposing and implementing upgrades to existing
  tools and processes to enhance analysis
  techniques and quality of results
• developing and implementing scripts to
  manipulate, format, parse, analyze, and display
  genome sequence data and developing new
  strategies for analysis and presentation of
  results.
• Requirements
• a bachelor's degree in biology or related field
• at least three years of experience in DNA
  sequencing and sequence analysis.
• Must possess solid knowledge of sequencing
  software and public sequencing databases.
• Knowledge of bioinformatics tools helpful.

• http//sh.webhire.com/servlet/av/jd?ai631ji2285
  147snI

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Bioinformatics Analyst

• Responsibilities
• The Bioinformatics Analyst will process sequence
  data and apply quality control measures for
  generating high quality raw sequence and
  assembled data from next generation sequencing
  technologies.?
• Will perform whole genome alignments using
  existing alignment tools, including BLAST, mummer
  and patternhunter Perform mapping and
  post-mapping analysis with short reads using
  third-party and internally developed tools.?
• Responsible for receiving, processing and
  managing sequence data.?
• Evaluate new methodologies and tools and improve
  data processing and quality control protocols.?
• Develop suitable metrics for reporting the
  completeness and quality of the sequence
  delivered to the customers.? 
• Requirements
• B.?S.? in biology, computer science,
  bioinformatics or related field, or equivalent
  combination of education and experience
• A minimum of 2 years experience in genomics and
  bioinformatics-related work.?
• Proficiency in Unix and experience in one or more
  of these programming languages -perl, SQL, jython
  and java is required.?
• Familiar with the use of commonly-used sequence
  analysis tools and genomic databases
• Willing to multi-task and respond to new
  challenges as required.?
• Excellent communication skills.?
• Hands-on experience in a research or production
  environment

http//jobview.monster.com/getjob.aspx?JobID78527
133JobTitleBioinformaticsAnalystbrd1qbioinf
ormaticscyuslid316re130AVSDM2009-01-0912
3a563a00pg1seq11fseo1isjs1re1000
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Business Systems Analyst

• Responsibilities
• The ideal candidate should be a highly motivated
  team player with a strong understanding of
  informatics solutions to biology and chemistry,
  especially in the area of data visualization/?stat
  istical analysis and with proven record of
  building/?integrating effective tools for
  scientists to help them in their daily work.?
• Actively work with scientists/?computational
  biologists in a disease area to understand their
  needs
• Define proper data analysis solution(s) to meet
  their scientific needs
• Perform rapid prototyping to refine the
  requirements with proper documentation
• Work with internal and external software teams,
  where appropriate to design/?implement proper
  solutions to meet scientists' needs
• Work either as a team member or lead a team to
  deliver data analysis platforms to
  scientists/?computational biologists
• Work effectively with different NITAS groups to
  ensure a globally consistent implementation
  scheme.?
• Requirements
• Bachelor's degree in computer science, Biology,
  Bioinformatics or comparable qualification
• At least 3-5 years hands-on experience on data
  analysis in a drug discovery, scientific or
  biotech environment
• Strong communications and interpersonal skills
• Proven capabilities interacting with scientists
  and being customer service oriented
• Ability to work independently and/?or as part of
  a team
• Familiarity with scientific LIMS such as
  ActivityBase, and data visualization/?analysis
  tools such as Spotfire
• Solid understanding of relational databases and
  familiarity with Oracle and/?or SQL server
• Good understanding in fundamentals of software
  engineering.?

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Summary

• Wide variety of jobs
• Biology, especially molecular biology and
  genetics
• Some statistics
• Computer skills
• UNIX
• Bioinformatics Tools
• Database (SQL)
• Some Programming
• Web
• Bioinformatics can be a rewarding career path

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National Resource for Biomedical Supercomputing