Genomics for Librarians

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Genomics for Librarians
Stuart M. Brown, Ph.D. Director, Research
Computing, NYU School of Medicine
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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 Human Genome Project
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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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A review of some basic genetics
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DNA

• 4 bases (G, C, T, A)
• base pairs
• G--C
• T--A
• genes
• non-coding regions

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Decoding Genes
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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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Genomics

• What is Genomics?
• An operational definition
• The application of high throughput automated
  technologies to molecular biology.
• A philosophical definition
• A wholistic or systems approach to the study of
  information flow within a cell.

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Genomics make LOTS of data!

• Investigators need complex databases just to
  manage their own experiments
• Biologists need to know how to do data mining to
  answer even simple questions in these huge data
  sets
• Librarians understand the challenges of storage
  and searching of large amounts of data

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New Biology New Librarians?

• How do Genomics and Bioinformatics overlap or
  interact with Library Science?
• The NCBI (Natl. Center for Biotechnology
  Information), the home of GenBank, is part of
  the National Library of Medicine
• We store and organize genes like Journal articles
  - accession number, annotation, etc.
• A big part of bioinformatics involves keyword
  searches and SQL queries in relational databases

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Bioinformatics is Not Library Science

• We are NOT cataloging a set of known information
• Programming and complex algorithms - pattern
  matching, string matching, biostatistics
• Data mining and multi-dimensional visualization
  tools
• Uncertainty of the data and constant revision of
  the known
• Genes are guesses based on complex algorithms,
  not books on the shelf

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Raw Genome Data
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BLAST Similarity Search

• gbBE588357.1BE588357 194087 BARC 5BOV Bos
  taurus cDNA 5'.
• Length 369
• Score 272 bits (137), Expect 4e-71
• Identities 258/297 (86), Gaps 1/297 (0)
• Strand Plus / Plus
• 
  
• Query 17 aggatccaacgtcgctccagctgctcttgacgactccac
  agataccccgaagccatggca 76
• 
  
• Sbjct 1 aggatccaacgtcgctgcggctacccttaaccact-cgc
  agaccccccgcagccatggcc 59
• 
  
• Query 77 agcaagggcttgcaggacctgaagcaacaggtggagggg
  accgcccaggaagccgtgtca 136
• 
  
• Sbjct 60 agcaagggcttgcaggacctgaagaagcaagtggagggg
  gcggcccaggaagcggtgaca 119
• 
  
• Query 137 gcggccggagcggcagctcagcaagtggtggaccaggcc
  acagaggcggggcagaaagcc 196

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Multiple Alignment
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Protein domains (Pattern analysis)
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Clustering (Phylogenetics)
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UCSC
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The Challenge of New Data Types (Genomics)

• 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
• Regulatory Networks

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Biological Information
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Microarray Technology
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Spot your own Chip (plans available for free
from Pat Browns website)
Robot spotter
Ordinary glass microscope slide
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cDNA spotted microarrays
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Goal of Microarray experiments

• Microarrays are a very good way of identifying a
  bunch of genes involved in a disease process
• Differences between cancer and normal tissue
• Tuberculosis infected vs resistant lung cells
• Mapping out a pathway
• Co-regulated genes
• Finding function for unknown genes
• Involved these processes

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Proteomics

• Identify all of the proteins in an organism
• Potentially many more than genes due to
  alternative splicing and post-translational
  modifications
• Quantitate in different cell types and in
  response to metabolic/environmental factors
• Protein-protein interactions

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Yeast ProteomeJeong H, Mason SP, A.-L
BarabasiNature 411 (2001) 40-41
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Human Genetic Variation

• Every human has essentially the same set of genes
• But there are different forms of each gene --
  known as alleles
• blue vs. brown eyes
• genetic diseases such as cystic fibrosis or
  Huntingtons disease are caused by dysfunctional
  alleles

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• Alleles are created by mutations in the DNA
  sequence of one person - which are passed on to
  their descendants

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High-Throughput Genotyping
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Relate genes to Organisms

• Diseases
• OMIM Human Genetic Disease
• Metabolic and regulatory pathways
• KEGG
• Cancer Genome Project

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Human Alleles

• The OMIM (Online Mendelian Inheritance in Man)
  database at the NCBI tracks all human mutations
  with known phenotypes.
• It contains a total of about 2,000 genetic
  diseases and another 11,000 genetic loci with
  known phenotypes - but not necessarily known gene
  sequences
• It is designed for use by physicians
• can search by disease name
• contains summaries from clinical studies

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Training "computer savvy" scientists

• Know the right tool for the job
• Get the job done with tools available
• Network connection is the lifeline of the
  scientist
• Jobs change, computers change, projects change,
  scientists need to be adaptable

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Why teach genomics in undergraduate (or Medical)
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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Long Term Implications

• A "periodic table for biology" will lead to an
  explosion of research and discoveries - we will
  finally have the tools to start making systematic
  analyses of biological processes (quantitative
  biology).
• Understanding the genome will lead to the
  ability to change it - to modify the
  characteristics of organisms and people in a wide
  variety of ways

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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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www.GenomicsHelp.com