1

Introduction to Bioinformatics

2

What is Bioinformatics?

3

NIH – definitions

What is Bioinformatics? - Research, development, and application of computational tools and approaches for expanding the use of biological, medical, behavioral, and health data, including the means to acquire, store, organize, archive, analyze, or visualize such data.

What is Computational Biology? - The development and application of analytical and theoretical methods, mathematical modeling and computational simulation techniques to the study of biological, behavioral, and social data.

on molecular

4

NSF – introductionLarge databases that can be accessed and analyzed with sophisticated tools have become central to biological research and education. The information content in the genomes of organisms, in the molecular dynamics of proteins, and in population dynamics, to name but a few areas, is enormous. Biologists are increasingly finding that the management of complex data sets is becoming a bottleneck for scientific advances. Therefore, bioinformatics is rapidly become a key technology in all fields of biology.

5

NSF – mission statementThe present bottlenecks in bioinformatics include the education of biologists in the use of advanced computing tools, the recruitment of computer scientists into this evolving field, the limited availability of developed databases of biological information, and the need for more efficient and intelligent search engines for complex databases.

6

NSF – mission statementThe present bottlenecks in bioinformatics include the education of the education of biologists in the use of advanced computing toolsbiologists in the use of advanced computing tools, the recruitment of computer scientists into this evolving field, the limited availability of developed databases of biological information, and the need for more efficient and intelligent search engines for complex databases.

7

Molecular Bioinformatics

Molecular Bioinformatics involves the use of computational tools to discover new information in complex data sets (from the one-dimensional information of DNA through the two-dimensional information of RNA and the three-dimensional information of proteins, to the four-dimensional information of evolving living systems).

Bioinformatics (Oxford English Dictionary):

The branch of science concerned with information and information flow in biological systems, esp. the use of computational methods in genetics and genomics.

8

Biologists collect molecular data: DNA & Protein sequences,gene expression, etc.

Computer scientists (+Mathematicians, Statisticians, etc.)Develop tools, softwares, algorithms to store and analyze the data.

BioinformaticiansStudy biological questions by analyzing molecular data

The field of science in which biology, computer science and information technology merge into a single discipline

9

Some biological background….

A biologist

10

The hereditary information of all living organisms, with the exception of some viruses, is carried by deoxyribonucleic acid (DNA) molecules.

2 purines:2 purines: 2 pyrimidines:2 pyrimidines:

adenine (A)adenine (A) cytosine (C)cytosine (C)guanine (G)guanine (G) thymine (T)thymine (T)

two ringstwo rings one ringone ring11

Eukaryotes may have up to 3 subcellular genomes: 1. Nuclear2. Mitochondrial 3. Plastid

Bacteria have either circular or linear genomes and may also carry plasmids

The entire complement of genetic material carried by an individual is called the genome.

Human chromosomes

Circular genome12

Central dogma: DNA makes RNA makes Protein

Modified dogma: DNA makes DNA and RNA, RNA makes DNA, RNA an Protein

13

Amino acids - The protein building blocks

14

15

Any region of the DNA sequence can, in principle, code for six different amino acid sequences, because any one of three different reading frames can be used to interpret each of the two strands.

16

Protein folding

A human Hemoglobin:

17

How does it all looks like on a computer monitor?

18

A cDNA sequence

>gi|14456711|ref|NM_000558.3| Homo sapiens hemoglobin, alpha 1 (HBA1), mRNAACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC

19

A cDNA sequence (reading frame)

A protein sequence

>gi|14456711|ref|NM_000558.3| Homo sapiens hemoglobin, alpha 1 (HBA1), mRNA

ACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACC

GTTAAGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC

>gi|4504347|ref|NP_000549.1| alpha 1 globin [Homo sapiens]

MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR

20

ACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGCACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGCACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGCGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGCACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCG...

And, a whole genome…

21

E. coli 4.6 x 106 nucleotides

– Approx. 4,000 genes

Yeast 15 x 106 nucleotides

– Approx. 6,000 genes

Human 3 x 109 nucleotides

– Approx. 30,000 genes

Smallest human chromosome 50 x 106 nucleotides

How big are whole genomes?

22

What do we actually do with bioinformatics?

23

Sequence assembly

(next generation sequencing)

24

Genome annotation

25

Molecular evolution

Smith et al. (2009) Nature 459, 1122-1125

Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic

26

Analysis of gene expression

Gene expression profile of relapsing versus non-relapsing Wilms tumors. A set of 39 genes discriminates between the two classes of tumors.

(http://www.biozentrum2.uni-wuerzburg.de/, Prof. Gessler)27

Analysis of regulation

Toledo and Bardot (2009) Nature 460, 466-467

28

Protein structure predictionProtein docking

29

Luscombe, Greenbaum, Gerstein (2001)

30

31

From DNA to Genome

Watson and Crick DNA model

Sanger sequences insulin protein

Sanger dideoxy DNA sequencing

PCR (Polymerase Chain Reaction)

1955

1960

1965

1970

1975

1980

1985

ARPANET (early Internet)

PDB (Protein Data Bank)

Sequence alignment

GenBank database

Dayhoff’s Atlas

32

1995

1990

2000

SWISS-PROT database

NCBI

World Wide Web

BLAST

FASTA

EBI

Human Genome Initiative

First human genome draft

First bacterial genome

Yeast genome

33

The first protein sequence reported was that of bovine insulin in 1956, consisting of 51 residues.

Origin of bioinformatics and biological databases:

Nearly a decade later, the first nucleic acid sequence was reported, that of yeast tRNAalanine with 77 bases.

34

In 1965, Dayhoff gathered all the available sequence data to create the first bioinformatic database (Atlas of Protein Sequence and Structure).

The Protein DataBank followed in 1972 with a collection of ten X-ray crystallographic protein structures. The SWISSPROT protein sequence database began in 1987.

35

Nucleotides

36

as of August 2011:

Eukaryotes 37

Prokaryotes 1708

Total 1745

Complete Genomes

37

What can we do with sequences and other type of molecular information?

38

Annotation

Open reading frames

Functional sites

Structure, function

39

CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG

CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA

CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC

AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA

AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA

TAT GGA CAA TTG GTT TCT TCT CTG AAT ......

.............. TGAAAAACGTA

40

CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG

CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA

CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC

AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA

AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA

TAT GGA CAA TTG GTT TCT TCT CTG

AAT .................................

.............. TGAAAAACGTA

TF binding sitepromoter

Ribosome binding Site

ORF = Open Reading FrameCDS = Coding Sequence

Transcription

Start Site

41

Comparativegenomics

Comparing ORFs

Identifying orthologs

Inferences on structure and function

Comparing functional sites

Inferences on regulatorynetworks

42

Similarity profiles

Researchers can learned a great deal about the structure and function of human genes by examining their counterparts in model organisms.

43

Xenopus MALWMQCLP-LVLVLLFSTPNTEALANQHLBos MALWTRLRPLLALLALWPPPPARAFVNQHL **** : * *.*: *:..* :. *:****

Xenopus CGSHLVEALYLVCGDRGFFYYPKIKRDIEQBos CGSHLVEALYLVCGERGFFYTPKARREVEG ***************:***** ** :*::*

Xenopus AQVNGPQDNELDG-MQFQPQEYQKMKRGIVBos PQVG---ALELAGGPGAGGLEGPPQKRGIV .**. ** * * *****

Xenopus EQCCHSTCSLFQLENYCNBos EQCCASVCSLYQLENYCN **** *.***:*******

Alignment preproinsulin

44

45

Ultraconserved Elements in the Human Genome Gill Bejerano, Michael Pheasant, Igor Makunin, Stuart Stephen, W. James Kent, John S. Mattick, & David Haussler (Science 2004. 304:1321-1325)There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development.

There are 156 intergenic, untranscribed, ultraconserved segments

46

Junk is real!

Junk:Junk:Supporting evidenceSupporting evidence

47

Functionalgenomics

Genome-wide profiling of:• mRNA levels• Protein levels

Co-expression of genesand/or proteins

Identifying protein-protein interactions

Networks of interactions

48

Understanding the function of genes and other Understanding the function of genes and other parts of the genomeparts of the genome

49

Structural genomics

Assign structure to all proteins encoded in a genome

Biological databases

50

Database or databank?

Initially

• Databank (in UK)• Database (in the USA)

Solution

• The abbreviation db

51

What is a Database?

A structured collection of data held in computer storage; esp. one

that incorporates software to make it accessible in a variety of ways;

transf., any large collection of information.

database management: the organization and manipulation of data in

a database.

database management system (DBMS): a software package that

provides all the functions required for database management.

database system: a database together with a database

management system.

Oxford Dictionary52

What is a database?• A collection of data

– structured – searchable (index) -> table of contents

– updated periodically (release) -> new edition

– cross-referenced (hyperlinks) -> links with other db

• Includes also associated tools (software) necessary for access, updating, information insertion, information deletion….

• Data storage management: flat files, relational databases…

53

Database: a « flat file » example

Accession number: 1

First Name: Amos

Last Name: Bairoch

Course: Pottery 2000; Pottery 2001;

//

Accession number: 2

First Name: Dan

Last name: Graur

Course: Pottery 2000, Pottery 2001; Ballet 2001, Ballet 2002

//

Accession number 3:

First Name: John

Last name: Travolta

Course: Ballet 2001; Ballet 2002;

//

• Easy to manage: all the entries are visible at the same time !

Flat-file database («  flat file, 3 entries  »):

54

Database: a « relational » example

Teacher Accession number

Education

Amos 1 Biochemistry

Dan 2 Genetics

John 3 Scientology

Course Year Involved teachers

Advanced Pottery

2000; 2001 1; 2

Ballet for Fat People

2001; 2002 2; 3

Relational database (« table file »):

55

Why biological databases?• Exponential growth in biological data.

• Data (genomic sequences, 3D structures, 2D gel analysis, MS analysis, Microarrays….) are no longer published in a conventional manner, but directly submitted to databases.

• Essential tools for biological research. The only way to publish massive amounts of data without using all the paper in the world.

56

Distribution of sequences

• Books, articles 1968 -> 1985• Computer tapes 1982 -> 1992• Floppy disks 1984 -> 1990• CD-ROM 1989 ->• FTP 1989 ->• On-line services 1982 -> 1994• WWW 1993 ->• DVD 2001 ->

57

Some statistics• More than 1000 different ‘biological’ databases

• Variable size: <100Kb to >20Gb– DNA: > 20 Gb

– Protein: 1 Gb

– 3D structure: 5 Gb

– Other: smaller

• Update frequency: daily to annually to seldom to forget about it.

• Usually accessible through the web (some free, some not)

58

Some databases in the field of molecular biology…

AATDB, AceDb, ACUTS, ADB, AFDB, AGIS, AMSdb, ARR, AsDb, BBDB, BCGD, Beanref, Biolmage,

BioMagResBank, BIOMDB, BLOCKS, BovGBASE,BOVMAP, BSORF, BTKbase, CANSITE, CarbBank,

CARBHYD, CATH, CAZY, CCDC, CD4OLbase, CGAP,ChickGBASE, Colibri, COPE, CottonDB, CSNDB, CUTG,

CyanoBase, dbCFC, dbEST, dbSTS, DDBJ, DGP, DictyDb,Picty_cDB, DIP, DOGS, DOMO, DPD, DPlnteract, ECDC,ECGC, EC02DBASE, EcoCyc, EcoGene, EMBL, EMD db,

ENZYME, EPD, EpoDB, ESTHER, FlyBase, FlyView,GCRDB, GDB, GENATLAS, Genbank, GeneCards,

Genline, GenLink, GENOTK, GenProtEC, GIFTS,GPCRDB, GRAP, GRBase, gRNAsdb, GRR, GSDB,

HAEMB, HAMSTERS, HEART-2DPAGE, HEXAdb, HGMD,HIDB, HIDC, HlVdb, HotMolecBase, HOVERGEN, HPDB,HSC-2DPAGE, ICN, ICTVDB, IL2RGbase, IMGT, Kabat,

KDNA, KEGG, Klotho, LGIC, MAD, MaizeDb, MDB,Medline, Mendel, MEROPS, MGDB, MGI, MHCPEP5

Micado, MitoDat, MITOMAP, MJDB, MmtDB, Mol-R-Us,MPDB, MRR, MutBase, MycDB, NDB, NRSub, 0-lycBase,OMIA, OMIM, OPD, ORDB, OWL, PAHdb, PatBase, PDB,

PDD, Pfam, PhosphoBase, PigBASE, PIR, PKR, PMD,PPDB, PRESAGE, PRINTS, ProDom, Prolysis, PROSITE,

PROTOMAP, RatMAP, RDP, REBASE, RGP, SBASE,SCOP, SeqAnaiRef, SGD, SGP, SheepMap, Soybase,SPAD, SRNA db, SRPDB, STACK, StyGene,Sub2D,

SubtiList, SWISS-2DPAGE, SWISS-3DIMAGE, SWISS-MODEL Repository, SWISS-PROT, TelDB, TGN, tmRDB,

TOPS, TRANSFAC, TRR, UniGene, URNADB, V BASE,VDRR, VectorDB, WDCM, WIT, WormPep, YEPD, YPD,

YPM, etc .................. !!!!59

Categories of databases for Life Sciences

• Sequences (DNA, protein)• Genomics• Mutation/polymorphism• Protein domain/family• Proteomics (2D gel, Mass Spectrometry)• 3D structure• Metabolic networks• Regulatory networks• Bibliography• Expression (Microarrays,…)

• Specialized60

61

NCBI:http://www.ncbi.nlm.nih.gov

EBI:http://www.ebi.ac.uk/

DDBJ:http://www.ddbj.nig.ac.jp/

62

Bookshelf: A collection of searchable biomedical books linked to PubMed.

PubMed: Allows searching by author names, journal titles, and a new Preview/Index option. PubMed database provides access to over 12 million MEDLINE citations back to the mid-1960's. It includes History and Clipboard options which may enhance your search session.

PubMed Central: The U.S. National Library of Medicine digital archive of life science journal literature.

OMIM: Online Mendelian Inheritance in Man is a database of human genes and genetic disorders (also OMIA).

Literature Databases:

PubMed (Medline)

• MEDLINE covers the fields of medicine, nursing, dentistry,

veterinary medicine, public health, and preclinical sciences

• Contains citations from approximately 5,200 worldwide journals in

37 languages; 60 languages for older journals.

• Contains over 20 million citations since 1948

• Contains links to biological db and to some journals

• New records are

added to

PreMEDLINE daily!

65

• Alerting services– http://www.pubcrawler.ie/– http://www.biomail.org

A search by subject: “mitochondrion evolution”

68

Type in a Query term

• Enter your search words in the

query box and hit the “Go” button

http://www.ncbi.nlm.nih.gov/entrez/query/static/help/helpdoc.html#Searching

69

The Syntax …1. Boolean operators: AND, OR, NOT must be entered in

UPPERCASE (e.g., promoters OR response elements). The default is AND.

2. Entrez processes all Boolean operators in a left-to-right sequence. The order in which Entrez processes a search statement can be changed by enclosing individual concepts in parentheses. The terms inside the parentheses are processed first. For example, the search statement: g1p3 OR (response AND element AND promoter).

3. Quotation marks: The term inside the quotation marks is read as one phrase (e.g. “public health” is different than public health, which will also include articles on public latrines and their effect on health workers).

4. Asterisk: Extends the search to all terms that start with the letters before the asterisk. For example, dia* will include such terms as diaphragm, dial, and diameter.

70

Refine the Query• Often a search finds too many (or too few) sequences, so you

can go back and try again with more (or fewer) keywords in your query

• The “History” feature allows you to combine any of your past queries.

• The “Limits” feature allows you to limit a query to specific organisms, sequences submitted during a specific period of time, etc.

• [Many other features are designed to search for literature in MEDLINE]

71

You can search for a text term in sequence annotations or in MEDLINE abstracts, and find all articles, DNA, and protein sequences that mention that term.

Then from any article or sequence, you can move to "related articles" or "related sequences".

•Relationships between sequences are computed with BLAST

•Relationships between articles are computed with "MESH" terms (shared keywords)

•Relationships between DNA and protein sequences rely on accession numbers

•Relationships between sequences and MEDLINE articles rely on both shared keywords and the mention of accession numbers in the articles.

Related Items

72

73

74

A search by authors: “Esser” [au] AND “martin” [au]

A search by title word: “Wolbachia pipientis” [ti]

77

Database Search Strategies

• General search principles - not limited to sequence (or to biology).

• Start with broad keywords and narrow the search using more specific terms.

• Try variants of spelling, numbers, etc.

• Search many databases.

• Be persistent!!

78

Searching PubMed

• Structureless searches– Automatic term mapping

• Structured searches– Tags, e.g. [au], [ta], [dp], [ti]– Boolean operators, e.g. AND, OR, NOT, ()

• Additional features– Subsets, limits– Clipboard, history

79

Start working:

Search PubMed

1. cuban cigars

2. cuban OR cigars

3. “cuban cigars”

4. cuba* cigar*

5. (cuba* cigar*) NOT smok*

6. Fidel Castro

7. “fidel castro”

8. #6 NOT #7

80

“Details” and “History” in PubMed

81

“Details” and “History” in PubMed

82

The OMIM (Online Mendelian Inheritance in Man)

– Genes and genetic disorders– Edited by team at Johns Hopkins– Updated daily

83

MIM Number Prefixes

* gene with known sequence+ gene with known sequence and

phenotype# phenotype description, molecular

basis known% mendelian phenotype or locus,

molecular basis unknownno prefix other, mainly phenotypes with

suspected mendelian basis

84

Searching OMIM

• Search Fields– Name of trait, e.g., hypertension– Cytogenetic location, e.g., 1p31.6– Inheritance, e.g., autosomal dominant– Gene, e.g., coagulation factor VIII

85

OMIM search tags

All Fields [ALL]Allelic Variant [AV] or [VAR]Chromosome [CH] or [CHR]Clinical Synopsis [CS] or [CLIN]Gene Map [GM] or [MAP]Gene Name [GN] or [GENE]Reference [RE] or [REF]

86

87

Start working:

Search OMIM

How many types of hemophilia are there?

For how many is the affected gene known?

What are the genes involved in hemophilia A?

What are the mutations in hemophilia A?

88

Online Literature databases

1. How to use the UH online Library?

2. Online glossaries

3. Google Scholar

4. Google Books

5. Web of Science

89

How to use the online UH Library? http://info.lib.uh.edu/

90

91

Online Glossaries

Bioinformatics :http://www.geocities.com/bioinformaticsweb/glossary.htmlhttp://big.mcw.edu/

Genomics: http://www.geocities.com/bioinformaticsweb/genomicglossary.html

Molecular Evolution: http://workshop.molecularevolution.org/resources/glossary/

Biology dictionary: http://www.biology-online.org/dictionary/satellite_cells

Other glossaries, e.g., the list of phobias:http://www.phobialist.com/class.html

92

4. Google Scholarhttp://www.scholar.google.com/

93

Enables you to search specifically for scholarly literature, including peer-reviewed papers, theses, books, preprints, abstracts and technical reports from all broad areas of research.

What is Google Scholar?

94

Use Google Scholar to find articles from a wide variety of academic publishers, professional societies, preprint repositories and universities, as well as scholarly articles available across the web.

95

Google Scholar orders your search results by how relevant they are to your query, so the most useful references should appear at the top of the page

This relevance ranking takes into account the: full text of each article. the article's author, the publication in which the article appeared and how often it has been cited in scholarly literature.

96

What other DATA can we retrieve from the record?

97

98

99

5. Google Book Search

100

101

Start working:

Search Google Books

How many times is the tail of the giraffe mentioned in On the Origin of Species by Mr. Darwin?

102

6. Web of sciencehttp://http://apps.webofknowledge.com.ezproxy.lib.uh.edu/WOS_GeneralSearch_input.do?product=WOS&search_mode=GeneralSearch&SID=4FB7LbbLgDMhG9fDiLh&preferencesSaved=

103

104