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NCBI data, sliding window programs and dot plots. Sept. 25, 2012 - PowerPoint PPT Presentation
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NCBI data, sliding window programs and dot plots
Sept. 25, 2012
Learning objectives-Become familiar with OMIM and PubMed. Understand the difference between a research article and review article. Understand the concept of sliding window programs. Understand difference between identity, similarity and homology. Appreciate that proteins can be modular
Workshop-Learn how to use OMIM and obtain DNA and proteins sequences associated with diseases. Perform sliding window to compute %(G+C) as a function of position in sequence.
Homework due Tuesday, Oct. 2nd.
Primary public domain bioinformatics servers
Public DomainBioinformatics
Facilities
European BioinformaticsInstitute (EBI)
United Kingdom
National CenterFor Biotechnology
Information (NCBI)United States
GenomeNet
(KEGG & DDBJ)Japan
DatabasesAnalysis
ToolsDatabases
AnalysisTools
DatabasesAnalysis
Tools
NCBI ENTREZ
A platform that provides access to and links to databases with biological information
ENTREZPubMed
GenBank Proteindatabases
Genomes PopSet Taxonomy OMIMMedLine
NCBI ENTREZ
GenBank
Proteindatabases
Genomes
PopSet
Taxonomy
OMIM
MedLine Literature Database
Database of DNA sequences that have been collected toanalyze the evolutionary relatedness of a population.
Database of human genes and genetic disorders
Database of all publicly available DNA sequences
Database of amino acid sequences from Uniprot, Protein ResearchFoundation, PDB.
Database of genomes from organisms and viruses
Database of names of organisms with sequences in GenBank.
Literature DatabasesMedline/PubmedOMIMCSULA LibraryBookshelf (from NCBI)Melvyl (Books at UC Libraries)Other molecular life science databases Science Direct Pub Med Central Free Medical Journals LinkOut Journals Wiley InterScience
OMIM-Online Mendelian Inheritance in Man
A catalog of human genes linked to diseasesVictor A. McKusick at Johns Hopkins UniversityA good place to start when you want to research a certain disease or biological moleculeThis database is cross-referenced to PubMed and other NCBI-based databases
Sliding window
A sliding window-gathers information about properties of nucleotides or amino acids.
GCATATGCGCATATCCCGTCAATACCA
GCATATGCGCATATCCCGTCAATACCA
GCATATGCGCATATCCCGTCAATACCA
4
5
6
A simple example is to calculate the %(G+C) content within a window. Then move the window one nucleotide and repeat the calculation.
Sliding window
If the window is too small it is difficult to detect the trendof the measurement. If too large you could miss meaningfuldata.
Large window size
Small window size
%(G+C)
%(G+C)
Sequence number
Sequence number
Sliding window
Adapted from Zhao et al, BMC Genomics. 2007 Nov 7;8:403.
Amino acid characteristics
Amino Acid Hydrop. VALUEA 1.8C 2.5D -3.5E -3.5F 2.8G -0.4H -3.2I 4.5K -3.9L 3.8M 1.9N -3.5P -1.6Q -3.5R -4.5S -0.8T -0.7V 4.2W -0.9Y -1.3
Four levels of protein structure
1) Primary
2) Secondary
3) Tertiary
4) Quaternary
Linear sequence- AGHIPLLQ
Initial folding patterns-AGHIPLLQ TTT
Complex folding patterns-
Interactions between polypeptides
Kyte-Doolittle Hydropathy
– A sliding window software program [J. Mol. Biol. 157:105-132 (1982)].
The seven known membrane-spanning regions are numbered 1-7 in red on the plot. Note that this particular software program averaged the hydropathy values in the window (http://www.vivo.colostate.edu/molkit/hydropathy/index.html). The original program by Kyte and Doolittle summed the hydropathy values.
Dot Plot with window = 1
Window = 1
Note that 25% ofthe table will befilled due to randomchance. 1 in 4 chanceat each position
A T G C C T A G
A
T
G
C
C
T
A
G
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Dot Plot with window = 3
Window = 3The larger the windowthe more noise canbe filtered
What is thepercent chance thatyou will receive a match randomly? Onein (four)3
chance.(¼)3 * 100 = 1.56%
{
A T G C C T A G G A
T G C C T A G
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Do workshop #2
Answer questions 1-3
Evolutionary Basis of Sequence Alignment
1. Identity: Quantity that describes how muchtwo sequences are alike in the strictest terms.2. Similarity: Quantity that relates how much two amino acid sequences are alike.3. Homology: A conclusion drawn from datasuggesting that two genes share a commonevolutionary history.
Purpose of finding differences and similarities of amino acids in two proteins.
Infer structural information
Infer functional information
Infer evolutionary relationships
Modular nature of proteins
Proteins possess local regions of similarity.
Proteins can be thought of as assemblies of modular domains.
Two proteins that are similar in certain regions
Tissue plasminogen activator (PLAT)Coagulation factor 12 (F12).
Baxevanis and Ouellette, Bioinformatics, Wiley-Interscience, New York, 2001
The Dotter Program
• Program consists of three components:
•Sliding window
•A table that gives a score for each amino acid match
•A graph that converts the score to a dot of certain density (the higher the dot density the higher the score)
Dot plot of sequence alignment highlighting Kringle domain alignments. Adapted from Baxevanis, Ouellette: Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, 2nd Edition.
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