Post on 16-Aug-2020
1
Introduction to Bioinformatics
Dr. rer. nat. Jing Gong
Cancer Research center
Medicine School of Shandong University
2011.9.14
Introduction to Bioinformatics
2
Chapter 1
Introduction
Introduction to Bioinformatics
3
About me• Dr. rer. nat. Jing Gong• Bachelor Degree in Marine Biology at the China
Ocean University (former Qingdao Ocean University)
• Bachelor, Master & Doctoral Degree in Bioinformatics at the Ludwig MaximiliansUniversität München, Germany
• Affiliation: Cancer Research Center of SDU• Tel: 0531-88380202• Email: gongjing@sdu.edu.cn• Office: Dianjing Building, Rm.106, Baotuquan
Campus
Introduction to Bioinformatics
4
About this course• Schedule: 2011/9/14 - 2011/10/12, Mi. 14:00 - 18:00• Locus: 8#, first floor, west, Computer Pool • Homepage: http://1.51.212.243/bioinfo.html
• Table of Contents
Chapter 1 : Introduction Chapter 2 : Databases
Chapter 5 : Tree
Chapter 3 : Alignment Chapter 4 : Structure
My name is Lampy.
Introduction to Bioinformatics
5
Literatures:1. Bioinformatics - An Introduction, 2nd Edition, Jeremy Ramsden, 2009, Springer. 2. Bioinformatics For Dummies, 2nd Edition, Jean-Michel Claverie, Cedric Notredame, 2007, Wiley.
Introduction to Bioinformatics
6
Information Page Vocabulary ListInformation Page
Chapter 1, 2011/9/14
Dr. rer. nat. Jing GongAffiliation: Cancer Research Center of SDUTel: 0531-88380202Email: gongjing@sdu.edu.cnOffice: Dianjing Building, Rm.106, BaotuquanCampus
Schedule: 2011/9/14 - 2011/10/12, Mi. 14:00 - 18:00Place: 8#, first floor, west, Computer Pool
Course Homepage: http://1.51.212.243/bioinfo.html
Pubmed: http://www.ncbi.nlm.nih.gov/entrez/
ExPASy: http://expasy.org/
NCBI: http://www.ncbi.nlm.nih.gov/
PRI: http://pir.georgetown.edu
FASTA
FASTA (prounced FAST-Aye) stands forFAST-ALL, reflecting the fact that it canbe used for a fast protein ……
BLAST
Basic Local Alignment Search Tool. A sequence comparison algorithm optimized for speed used to search sequence dtabases ……
Alignment
The result of a comparison of two or more gene or protein sequences in order to determine their degree of base or amino acid…….
FASTA
FASTA (读作FAST-Aye) 代表FAST-ALL, 反映的实施是他能够用于快速的蛋白质比对或者快组的核苷比对。该程序……
BLAST
基本局部比对搜索工具。以速度优化算法为核心,搜索序列数
据库得到 佳局部比对结果。用替代矩阵和查新序列……
比对
两个甚至更多的基因或者蛋白质序列进行比较的结果,用以计算他们碱基或者氨基酸的相似度。序列比对用来决定两个甚至…….
Vocabulary
Chapter 1, 2011/9/14
Introduction to Bioinformatics
7
What is Bioinformatics?
biochemistry
biometrics
biophysics biohazards
biomathematics
bioterrorism
biopotato bioinformatics
Introduction to Bioinformatics
8
What is Bioinformatics? Interdisciplinary
a biology/medical researchers, just like you
a professional in the pharmaceutical industry
a policeman worrying about DNA testing
a computer scientist developing bio-databases
a consumer concerned about GMOs (Genetically Modified Organisms)
… …
Introduction to Bioinformatics
9
What is Bioinformatics?Definition:Bioinformatics – the science of collecting and analyzing complex biological data such as genetic codes. [Oxford Dictionary]
Bioinformatics – the computational branch of molecular biology. [Bioinformatics for Dummies]
Bioinformatics – the application of computer science and information technology to the field of biology and medicine. [Wikipedia]
Bioinformatics – the science of how information is generated, transmitted, received, and interpreted in biological systems, i.e. the application of information science to biology. [Bioinformatics-An Introduction]
A formel definition ?
Introduction to Bioinformatics
10
History of BioinformaticsIn 1809, French biologist Jean Baptiste Lamarck published “PhilosophieZoologique”. Lamarck stressed two main themes in his biological work:
1. The environment gives rise to changes in animals, i.e. changes through use and disuse.
2. Life was structured in an orderly manner and that many different parts of all bodies make it possible for the organic movements of animals.
“blind as a mole” “show your teeth” “birds have no teeth?” Jean Baptiste Lamarck (1744-1829)
Introduction to Bioinformatics
11
In 1859, English naturalist Charles Darwin published “On the Origin of Species by Means of Natural Selection, or the Preservation of FavouredRaces in the Struggle for Life”.
Charles Darwin (1809-1882)
History of Bioinformatics
Introduction to Bioinformatics
12
Gregor J. Mendel (1822-1884)
In 1866, Austrian scientist GregorMendel demonstrated that the inheritance of certain traits in pea plants follows particular patterns, now referred to as the laws of “Mendelian Inheritance”.
History of Bioinformatics
Introduction to Bioinformatics
13
Friedrich Miescher(1844-1895)
History of BioinformaticsIn 1869, Swiss physician and biologist Friedrich Miescher isolated DNA from the white blood cells at Felix Hoppe-Seyler's laboratory at the University of Tübingen, Germany.
Nuclei Nuclein Nucleic acid DNA
Introduction to Bioinformatics
14
Thomas Hunt Morgan, American geneticist, famous for his experimental research with the fruit fly by which he established the chromosome theory of heredity. He showed that genes are linked in a series on chromosomes and are responsible for identifiable, hereditary traits. Morgan’s work played a key role in establishing the field of genetics. He received the Nobel Prize for Physiology or Medicine in 1933.
Thomas H. Morgen(1866-1945)
nobel prize 1933
History of Bioinformatics
Introduction to Bioinformatics
15
In 1944, American physician and medical researcher Oswald Avery and his co-workers Colin MacLeod and Maclyn McCarty demonstrated that DNA is the material of which genes and chromosomes are made.
In his experiment he destroyed the lipids, ribonucleic acids, carbohydrates, and proteins. Transformation still occurred after this. Next he destroyed the deoxyribonucleic acid. Transformation did not occur.
Oswald Avery Colin MacLeod Maclyn McCarty(1877-1955) (1909-1972) (1911-2005)
History of Bioinformatics
Introduction to Bioinformatics
16
In 1950, American biochemist Erwin Chargaff noticed a pattern in the amounts of the four bases: adenine (A) , thymine (T) , cytosine (C) , guanine (G). He discovered that the amounts of adenine (A) and thymine (T) in DNA were roughly the same, as were the amounts ofcytosine (C) and guanine (G). This later became known as Chargaff's rule.
Erwin Chargaff (1905-2002)
History of Bioinformatics
%A = %T and %G = %C
Introduction to Bioinformatics
17
In 1953, James D. Watson and Francis Cricksuggested the first correct double-helix model of DNA structure in the journal Nature. Their double-helix model of DNA was based on a single X-ray diffraction image taken by Rosalind Franklin andMaurice Wilkins in 1952.
Rosalind Franklin(1920-1958)
James Waston(1928-)
nobel prize 1962
Francis Crick (1916-2004)
nobel prize 1962
Maurice Wilkins (1916-2004)
nobel prize 1962
History of Bioinformatics
Introduction to Bioinformatics
18
The sequence of 77 nucleotides of a yeast alanine tRNA was found by an American biochemist Robert W. Holley in 1965. Holley was awarded the 1968 Nobel Prize in Physiology or Medicine for describing the structure of this tRNA, linking DNA and protein synthesis.
History of Bioinformatics
Robert W. Holley (1922-1993)
nobel prize 1968
Introduction to Bioinformatics
19
Frederick Sanger (1918-)
nobel prize 1980
In 1977, Frederick Sanger and Colleagues introduced the “dideoxy” chain-termination method for sequencing DNA molecules, also known as the “Sanger method”. Hence, in 1980, he shared Nobel Prize in chemistry with Walter Gilbert.
Walter Gilbert(1932-)
nobel prize 1980
History of Bioinformatics
The key principle of the Sanger method was the use of dideoxynucleotide triphosphates (ddNTPs), as DNA chain terminators.
Introduction to Bioinformatics
20
Read protein sequence directly in the DNA sequence!
Central dogma of molecular biology was first articulated by Francis Crick in 1958 and re-stated in a Nature paper published in 1970. Francis Crick
(1916-2004)
History of Bioinformatics
Introduction to Bioinformatics
21
Marshall Warren Nirenberg shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" and describing how it operates in protein synthesis.
Marshall Warren Nirenberg
(1927-2010)nobel prize 1968
Har GobindKhorana (1922-)nobel prize 1968
Robert W. Holley (1922-1993)
nobel prize 1968
History of Bioinformatics
Robert W. Holley (1922-1993)
nobel prize 1968
Robert W. Holley (1922-1993)
nobel prize 1968
Introduction to Bioinformatics
22
Introduction to BioinformaticsEnglish Courses for Graduate Students
Amino acids are the building blocks of protein.
Amino acids are made of carbon, hydrogen, oxygen, nitrogen, and sulfur atoms.
A protein = C1200H2400O600N300S100
Protein is a nutrient needed by the human body for growth and maintenance.
History of Bioinformatics
23V
Y
W
T
S
P
F
M
K
L
I
H
G
E
Q
C
D
N
R
A
1-letter
ValineVal20
TyrosineTyr19
TrytophanTrp18
ThreonineThr17
SerineSer16
ProlinePro15
PhenylalaninePhe14
MethionineMet13
LysineLys12
LeucineLeu11
IsoleucineIle10
HistindineHis9
GlycineGly8
Glutamic acidGlu7
GlutamineGln6
CysteineCys5
Aspartic acidAsp4
AsparagineAsn3
ArginineArg2
AlanineAla1
Nmae3-letter# A given type of protein always contains the same number of total amino acids in the same proportion.
Amino acids are linked together as a chain. The first amino acid sequence of a protein, Insulin, was determined in 1951 by Dr. Sanger.insulin = MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN
insulin = (30 glycines + 44 alanines + 5 tyrosines + 14 glutamines + . . .)
Frederick Sanger (1918-)nobel prize 1958
Introduction to BioinformaticsEnglish Courses for Graduate Students
Amino acids are linked together as a chain. The first amino acid sequence of a protein, Insulin, was determined in 1951 by Dr. Sanger.insulin = MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN
Frederick Sanger (1918-)nobel prize 1958
History of Bioinformatics
24
Protein Sequence: MAVLD
The first 3D structure of a protein was determined in 1958 by Drs. Kendrewand Perutz, using the complicated technique of X-ray crystallography. Max Ferdinand
Perutz (1914-2002) nobel prize 1962
John CowderyKendrew (1917-1997)
nobel prize 1962
What Bioinformatics Can Do for You?Analyzing Protein Sequences
Introduction to BioinformaticsEnglish Courses for Graduate Students
25
In 1956, Symposium on Information Theory in Biology (Gatlinburg, USA).
In 1979, GenBank was established at Los Alamos National Laboratory (USA).
In 1982, nucleotide sequence database of European Molecular Biology Laboratory (EMBL) was created (Europe).
In 1986, DNA Data Bank of Japan (DDBJ) began data bank activities at NIG (Japan).
in the early 1990s, International Nucleotide Sequence Database Collaboration (INSDC) was founded in cooperation of Genebank/EMBL/DDBJ.
In 1987, a Chinese-American scientist LIN Hua-an first created the word “bioinformatics”. At the very beginning, he created the word “compbio”, then “bioinformatique”, and then “bio-informatics”. But at that time, the email title did not support the hyphen symbol, thus “bioinformatics” was born.
Since at least the late 1980s, the term “bioinformatics” has been primary used in genomics and genetics, particularly in those areas of genomics involving large-scale DNA sequencing.
Introduction to BioinformaticsEnglish Courses for Graduate Students
History of Bioinformatics
26
Introduction to BioinformaticsEnglish Courses for Graduate Students
History of Bioinformatics
27
Publicly funded project: Privately funded project
James D. Watson & Francis Collins President Clinton (2000) Craig Venter
1990 began, $3-billion 1998 began, $300-million
patented
feely available
2000 90%
2001 99%
2003 finished
2000 90%
2001 99%
2003 finished
Introduction to BioinformaticsEnglish Courses for Graduate Students
History of Bioinformatics
28
Introduction to BioinformaticsEnglish Courses for Graduate Students
History of Bioinformatics
29
AB SOLiDTM
4.0 SystemX 27
Illumina HiSeq 2000X 137
Beijing
Shanghai
Shenzhen
Introduction to BioinformaticsEnglish Courses for Graduate Students
History of Bioinformatics
30
What Bioinformatics Can Do for You?
Analyzing DNAs
Analyzing RNAs
Analyzing Proteins
Others: Pathway, Bioimaging, etc.
Introduction to BioinformaticsEnglish Courses for Graduate Students
31
1. Read the DNA sequence:ATGGAAGTATTTAAAGCGCCACCTATTGGGATATAAG
2. Decompose it into successive triplets:ATG GAA GTA TTT AAA GCG CCA CCT ATT GGG ATA TAA G . . .
3. Translate each triplet into the corresponding amino acid:M E V F K A P P I G I STOP
What Bioinformatics Can Do for You?Analyzing DNAs
Introduction to BioinformaticsEnglish Courses for Graduate Students
32
ATGGAAGTATTTAA……
MEVFKAP…
DNA
Protein
Database
Introduction to BioinformaticsEnglish Courses for Graduate Students
What Bioinformatics Can Do for You?Analyzing DNAs
33
What Bioinformatics Can Do for You?Analyzing RNAs
In the context of bioinformatics, there are only two important differences between RNA and DNA:
RNA differs from DNA by one nucleotide.
RNA comes as a single strand.
Introduction to BioinformaticsEnglish Courses for Graduate Students
34
Even though RNA molecules consist of single strands of nucleotides, theirnatural urge for pairing with complementary sequences is still there.
Hairpin shapes are the basic elements of RNA secondary structure; they’re made up of loops (the unpaired C-U) and stems (the paired regions).
All transfer RNAs (tRNAs) assemble themselves into a shape like a cloverleaf.
What Bioinformatics Can Do for You?Analyzing RNAs
Introduction to BioinformaticsEnglish Courses for Graduate Students
35
What Bioinformatics Can Do for You?Analyzing ProteinsProtein Structure Determination:
Experimental Methods
Computational MethodsDe novo method, Homology Modeling, Threading, and ensemble method.
X-ray Crystallography Nuclear Magnetic Resonance (NMR)
Introduction to BioinformaticsEnglish Courses for Graduate Students
The first 3D structure of a protein was determined in 1958 using X-ray crystallography.
36
Maestro
Structure
SequenceVMD
Function
Pymol
What Bioinformatics Can Do for You?Analyzing Proteins
Introduction to BioinformaticsEnglish Courses for Graduate Students
37
What Bioinformatics Can Do for You?Analyzing Protein Sequences
Drug Design:
• Virtual Screen
• DockingVirtual screening involves the rapid in silico assessment of large libraries of chemical structures in order to identify those structures which are most likely to bind to a drug target, typically a protein receptor or enzyme.
Introduction to BioinformaticsEnglish Courses for Graduate Students
38
What Bioinformatics Can Do for You?Analyzing Protein Sequences
Molecular dynamics (MD) is a computer simulation of physical movements of atoms and molecules.
Super-computer
500-aa protein, 1 ns (10-9 s), 120 Cores :5 hours
Introduction to BioinformaticsEnglish Courses for Graduate Students
39
Introduction to BioinformaticsEnglish Courses for Graduate Students
What Bioinformatics Can Do for You?Analyzing Protein Sequences
Bavaria Supercomputing Centre• Linux Cluster: 2007, 753 notes, 5646 cores,
43 Tera Float/s
• HLRB II: 2007, 9728 cores, 62 Tera Float/s
• SuperMUC: 2012, 140000 cores, 3 Peta Float/s
天河一号: 2.5 Peta Float/s, No.1 in the world
Linux Cluster HLRB II SuperMUC
40
What Bioinformatics Can Do for You?Others: Pathway, Bioimaging, etc.
Introduction to BioinformaticsEnglish Courses for Graduate Students
CT
magnetic resonance
statistic graph
41
How Most People Use Bioinformatics?
Making a Multiple Protein Sequence Alignment with ClustalW
Becoming an Instant Expert with PubMed
Retrieving Protein Sequences
Retrieving DNA Sequences
Using BLAST to Compare Your Protein Sequence
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a 3D protein structure
42
How Most People Use Bioinformatics?
Gene Sequence
Specialistin
Bioinformatics
Great! It’s dUTPase.
But, what’s dUTPase.
Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
43
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMedhttp://www.ncbi.nlm.nih.gov/entrez/
Introduction to BioinformaticsEnglish Courses for Graduate Students
dUTPase
44
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
45
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
46
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
47
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
48
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
49
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Author Name
Introduction to BioinformaticsEnglish Courses for Graduate Students
50
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Author Name + Topic
Introduction to BioinformaticsEnglish Courses for Graduate Students
51
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
52
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
53
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
1
2
3
Introduction to BioinformaticsEnglish Courses for Graduate Students
54
How Most People Use Bioinformatics?Pubmed ID
PublicationDate
Title
Page
Abstracts
Laboratory address
authors
Internal structure of a database record:
The information is spread out over separate sections, called fields.
Introduction to BioinformaticsEnglish Courses for Graduate Students
55
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Search “Down” in field “Author [AU]”
Search “Down” in field “Title [TI]”
Search “Down” in field “Laboratory address [AD]”
Search “Down”everywhere
Introduction to BioinformaticsEnglish Courses for Graduate Students
56
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Beijing
Using fields to find experts near you :
Tel : 86 - 10 - 6275-5002 Fax : 86 - 10 - 6276-2292 New Life Science Building, Peking University, Summer Palace Road No. 5, Beijing, P. R. China 100871
1
2
3
BeijingBeijing
Introduction to BioinformaticsEnglish Courses for Graduate Students
57
How Most People Use Bioinformatics?
Searching PubMedusing limits
Introduction to BioinformaticsEnglish Courses for Graduate Students
Becoming an Instant Expert with PubMedhttp://www.ncbi.nlm.nih.gov/entrez/
dUTPase
58
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Searching PubMedusing limits
Introduction to BioinformaticsEnglish Courses for Graduate Students
59
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
Introduction to BioinformaticsEnglish Courses for Graduate Students
60
How Most People Use Bioinformatics?Becoming an Instant Expert with PubMed
A few more tips about PubMed : How to get the most out of your query:
• quoted queries (for example, “down syndrome”)• logical connectors: AND, OR, NOT (for example,
dUTPase[TI] OR pyrophosphatase[TI] NOT Smith[AU])• initials to proper names (for example, “Abergel C”)• PubMed Identifier (the number in the PMID field)• deselection of the Limit box when starting a new search.• Related Articles link
How to get the most out of your query:• Names ranking beyond the 10th place in author’s list for older papers (before 1995). • Papers recorded before 1965. • Abstracts for most references recorded before 1976.
Introduction to BioinformaticsEnglish Courses for Graduate Students
61
How Most People Use Bioinformatics?
acquire some preliminary information about a particular function that you’re interested in — dUTPase.
find out more about it by retrieving a few examples of protein sequencesthat perform this function in E. coli.
Retrieving Protein Sequences http://expasy.org/
ExPASy
Introduction to BioinformaticsEnglish Courses for Graduate Students
62
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Prof. Amos Bairoch
dUTPase coli
Introduction to BioinformaticsEnglish Courses for Graduate Students
63
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
64
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
65
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
66
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
67
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
1 2 3
Introduction to BioinformaticsEnglish Courses for Graduate Students
68
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
69
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
1 2 3
Introduction to BioinformaticsEnglish Courses for Graduate Students
70
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
71
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
72
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
73
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Tab
Excel
FASTA
Introduction to BioinformaticsEnglish Courses for Graduate Students
74
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
75
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
Introduction to BioinformaticsEnglish Courses for Graduate Students
76
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
“Cross-references”point to data collections other than UniProtKB.
Introduction to BioinformaticsEnglish Courses for Graduate Students
77
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
“sequences” provides you with the actual amino acid sequence of the protein.
Save this sequence on your Desktop as “P06968.fasta”.
right click
Introduction to BioinformaticsEnglish Courses for Graduate Students
78
How Most People Use Bioinformatics?Retrieving Protein Sequences http://expasy.org/
What is FASTA? (has anything to do with PASTA?)
FASTA is the name of a popular sequence alignment and database scanning program created by W.R. Pearson and D.J. Lipman in 1988. Its legacy is the FASTA format which is now ubiquitous in bioinformatics.
The sequence in FASTA format :
>P06968 My_Sequence_NameARCGTCRGCKINTANDRGCKINTANDCKINTANDARCGTCRGCKINTANDRGCKINTAND
The line starting with > (the definition line) contains a unique identifier followed by an optionalshort definition. The lines that follow it contain the DNA or protein sequence (in one-lettercode) until the next > symbol indicates the beginning of a new sequence.
Introduction to BioinformaticsEnglish Courses for Graduate Students
79
How Most People Use Bioinformatics?
acquire some preliminary information about a particular function that you’re interested in — dUTPase.
find out more about it by retrieving a few examples of protein sequencesthat perform this function in E. coli.ExPASy
retrieve DNA sequence relevant to dUTPase protein of E. coli.
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieving DNA Sequences
80
How Most People Use Bioinformatics?Retrieving DNA Sequences http://expasy.org/
P06968
Introduction to BioinformaticsEnglish Courses for Graduate Students
81
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieving DNA Sequences http://expasy.org/
82
How Most People Use Bioinformatics?Retrieving DNA Sequences
Introduction to BioinformaticsEnglish Courses for Graduate Students
83
How Most People Use Bioinformatics?Retrieving DNA Sequences
Introduction to BioinformaticsEnglish Courses for Graduate Students
84
How Most People Use Bioinformatics?Retrieving DNA Sequences
Introduction to BioinformaticsEnglish Courses for Graduate Students
85
How Most People Use Bioinformatics?Retrieving DNA Sequences
……
1. Summary Section
2. Reference Section
Introduction to BioinformaticsEnglish Courses for Graduate Students
From UniprotKB: P06968 jump to
86
How Most People Use Bioinformatics?Retrieving DNA Sequences
……
3. Features Section• promoter elements• ribosome binding
sites (RBS)• protein coding
segments (CDS)……
4. Sequence Section
Range of UTPaseORF (CDS)
ORF translation
Introduction to BioinformaticsEnglish Courses for Graduate Students
87
How Most People Use Bioinformatics?Retrieving DNA Sequences
……
1. Summary Section
2. Reference Section
Introduction to BioinformaticsEnglish Courses for Graduate Students
88
How Most People Use Bioinformatics?Retrieving DNA Sequences
……
1. Summary Section
2. Reference Section
Introduction to BioinformaticsEnglish Courses for Graduate Students
89
How Most People Use Bioinformatics?
acquire some preliminary information about a particular function that you’re interested in — dUTPase.
find out more about it by retrieving a few examples of protein sequencesthat perform this function in E. coli.
Using BLAST to Compare Sequence
ExPASy
perform a BLAST search
Introduction to BioinformaticsEnglish Courses for Graduate Students
retrieve DNA sequence relevant to dUTPase protein of E. coli.
90
How Most People Use Bioinformatics?Using BLAST to Compare Sequence
What is BLAST?
BLAST (Basic Local Alignment Search Tool) – A sequencecomparison algorithm optimized for speed used to search sequence databases for optimal local alignments to a query.
BLASTn – BLASTn will search a DNA sequence against a DNA databank.
BLASTp – BLASTp will compare a protein sequence against the protein database of your choice.
BLASTx – BLASTx will translate a nucleic acid sequence in all six reading frames and compare all these against the protein database of your choice.
BLAST? – BLAST? ……
Introduction to BioinformaticsEnglish Courses for Graduate Students
91
How Most People Use Bioinformatics?Using BLAST to Compare Sequence http://www.ncbi.nlm.nih.gov/
Introduction to BioinformaticsEnglish Courses for Graduate Students
92
How Most People Use Bioinformatics?Using BLAST to Compare Sequence http://www.ncbi.nlm.nih.gov/
Introduction to BioinformaticsEnglish Courses for Graduate Students
93
How Most People Use Bioinformatics?Using BLAST to Compare Sequence http://www.ncbi.nlm.nih.gov/
Open “P06968.fasta” at your Desktop, and paste the sequence here.
Give a name here.
1
2
3
http://1.51.212.243/P06968.fasta
Introduction to BioinformaticsEnglish Courses for Graduate Students
94
How Most People Use Bioinformatics?Using BLAST to Compare Sequence http://www.ncbi.nlm.nih.gov/
Introduction to BioinformaticsEnglish Courses for Graduate Students
95
How Most People Use Bioinformatics?Using BLAST to Compare Sequence http://www.ncbi.nlm.nih.gov/
Introduction to BioinformaticsEnglish Courses for Graduate Students
96
How Most People Use Bioinformatics?
E-value (form 0 to 1) close to 1 is a warning that the conclusion you might draw from the alignments is NOTreliable.
Introduction to BioinformaticsEnglish Courses for Graduate Students
97
How Most People Use Bioinformatics?
to see the alignment between your query sequence and the matching sequence of the protein that corresponds to this score.
to see the corresponding database entry.
Introduction to BioinformaticsEnglish Courses for Graduate Students
98
How Most People Use Bioinformatics?Using BLAST to Compare Sequence http://www.ncbi.nlm.nih.gov/
Introduction to BioinformaticsEnglish Courses for Graduate Students
99
How Most People Use Bioinformatics?Using BLAST to Compare Sequence http://www.ncbi.nlm.nih.gov/
Introduction to BioinformaticsEnglish Courses for Graduate Students
What is Alignment?
Alignment is the result of a comparison of two or more gene or protein sequences in order to determine their degree of base or amino acid similarity.
Pairwise Alignment
Multiple Alignment
100
How Most People Use Bioinformatics?
acquire some preliminary information about a particular function that you’re interested in — dUTPase.
find out more about it by retrieving a few examples of protein sequencesthat perform this function in E. coli.
Making a Multiple Sequence Alignment
ExPASy
perform a BLAST search
Introduction to BioinformaticsEnglish Courses for Graduate Students
retrieve DNA sequence relevant to dUTPase protein of E. coli.
perform a multiple
alignment
101
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment
Multiple alignments are used to :
• Identify sequence positions where specific amino acids really matter for the structural integrity or the function of a given protein
• Define specific sequence signatures for protein families• Classify sequences and build evolutionary trees
Introduction to BioinformaticsEnglish Courses for Graduate Students
102
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Introduction to BioinformaticsEnglish Courses for Graduate Students
103
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Introduction to BioinformaticsEnglish Courses for Graduate Students
104
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
http://1.51.212.243/multi.fasta
Get sequences under :http://1.51.212.243/multi.fasta
Select all
Copy
Introduction to BioinformaticsEnglish Courses for Graduate Students
105
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Paste
Introduction to BioinformaticsEnglish Courses for Graduate Students
106
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Introduction to BioinformaticsEnglish Courses for Graduate Students
107
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Introduction to BioinformaticsEnglish Courses for Graduate Students
* identical
: similar
. related
different
108
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Introduction to BioinformaticsEnglish Courses for Graduate Students
109
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Introduction to BioinformaticsEnglish Courses for Graduate Students
Conserved region
110
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Introduction to BioinformaticsEnglish Courses for Graduate Students
111
How Most People Use Bioinformatics?Making a Multiple Sequence Alignment http://pir.georgetown.edu
Introduction to BioinformaticsEnglish Courses for Graduate Students
112
How Most People Use Bioinformatics?
acquire some preliminary information about a particular function that you’re interested in — dUTPase.
find out more about it by retrieving a few examples of protein sequencesthat perform this function in E. coli.
Retrieve a protein structure
ExPASy
perform a BLAST search
perform a multiple
alignment
Introduction to BioinformaticsEnglish Courses for Graduate Students
retrieve DNA sequence relevant to dUTPase protein of E. coli.
retrieve a protein structure
113
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure dUTPase
protein sequence
DNA sequence
3D structure
114
How Most People Use Bioinformatics?
Beijing
Using fields to find experts near you :
Tel : 86 - 10 - 6275-5002 Fax : 86 - 10 - 6276-2292 New Life Science Building, Peking University, Summer Palace Road No. 5, Beijing, P. R. China 100871
BeijingBeijing
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure
115
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure
Su XD dUTPase
116
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure
117
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure
118
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure
119
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure Press leftbutton
120
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure Pressing left button
Action
Right-Click Jmol Menu
Left Click Select/DeselectResidue
Shift + Left Clickdrag mouse up or down / roll mouse middle button
Zoom
Left Click and Drag Rotate View
121
How Most People Use Bioinformatics?
Introduction to BioinformaticsEnglish Courses for Graduate Students
Retrieve a protein structure
122
How Most People Use Bioinformatics?Retrieve a protein structure
Introduction to BioinformaticsEnglish Courses for Graduate Students
Backbone by chain
123
Introduction to BioinformaticsEnglish Courses for Graduate Students