1. introduction to biology and bioinformatics · introduction to biology and bioinformatics...

1. INTRODUCTION TO BIOLOGY AND BIOINFORMATICS

BIOINFORMATICS COURSE

MTAT.03.239

11.09.2013

2 "Introduction to Bioinformatics"

Bioinformatics Course

Is a characteristic that distinguishes objects that have signaling and self-sustaining processes (i.e. living organism) to those that do not have it

Is a state of living characterized by capacity for metabolism, growth, reaction to stimuli, and reproduction

A diversity of life forms are found on Earth, eg. plants, animals, fungi, protists, archaea and bacteria

LIFE



WHAT IS BIOLOGY ?



http://www.tagxedo.com/app.html



BIOLOGY Is a study of life and living organisms

It brings together the structure, function, growth, origin, distribution, adaptation, interactions, taxonomy and evolution of living organism

AEROBIOLOGY, AGRICULTURE, ANATOMY, ASTROBIOLOGY, BIOCHEMISTRY, BIOENGINEERING, BIOINFORMATICS,

BIOMATHEMATICSOR, MATHEMATICAL BIOLOGY, BIOMECHANICS, BIOMEDICAL RESEARCH, BIOPHYSICS, BIOTECHNOLOGY, BUILDING BIOLOGY, BOTANY, CELLBIOLOGY, CONSERVATION BIOLOGY, CRYOBIOLOGY, DEVELOPMENTAL BIOLOGY, ECOLOGY, EMBRYOLOGY, ENTOMOLOGY, ENVIRONMENTAL BIOLOGY, EPIDEMIOLOGY, ETHOLOGY, EVOLUTIONARY BIOLOGY, GENETICS, HERPETOLOGY, HISTOLOGY, ICHTHYOLOGY, INTEGRATIVE BIOLOGY, LIMNOLOGY, MAMMALOGY, MARINE BIOLOGY, MICROBIOLOGY, MOLECULAR BIOLOGY, MYCOLOGY, NEUROBIOLOGY, OCEANOGRAPHY, ONCOLOGY, ORNITHOLOGY, POPULATION BIOLOGY, POPULATION ECOLOGY, POPULATION GENETICS, PALEONTOLOGY, PATHOBIOLOGY OR PATHOLOGY, PARASITOLOGY, PHARMACOLOGY, PHYSIOLOGY, PHYTOPATHOLOGY, PSYCHOBIOLOGY, SOCIOBIOLOGY, STRUCTURAL BIOLOGY, VIROLOGY

Is a study of life and living organisms

It brings together the structure, function, growth, origin, distribution, adaptation, interactions, taxonomy and evolution of living organism

AEROBIOLOGY, AGRICULTURE, ANATOMY, ASTROBIOLOGY, BIOCHEMISTRY, BIOENGINEERING, BIOINFORMATICS,

BIOMATHEMATICSOR, MATHEMATICAL BIOLOGY, BIOMECHANICS, BIOMEDICAL RESEARCH, BIOPHYSICS, BIOTECHNOLOGY, BUILDING BIOLOGY, BOTANY, CELLBIOLOGY, CONSERVATION BIOLOGY, CRYOBIOLOGY, DEVELOPMENTAL BIOLOGY, ECOLOGY, EMBRYOLOGY, ENTOMOLOGY, ENVIRONMENTAL BIOLOGY, EPIDEMIOLOGY, ETHOLOGY, EVOLUTIONARY BIOLOGY, GENETICS, HERPETOLOGY, HISTOLOGY, ICHTHYOLOGY, INTEGRATIVE BIOLOGY, LIMNOLOGY, MAMMALOGY, MARINE BIOLOGY, MICROBIOLOGY, MOLECULAR BIOLOGY, MYCOLOGY, NEUROBIOLOGY, OCEANOGRAPHY, ONCOLOGY, ORNITHOLOGY, POPULATION BIOLOGY, POPULATION ECOLOGY, POPULATION GENETICS, PALEONTOLOGY, PATHOBIOLOGY OR PATHOLOGY, PARASITOLOGY, PHARMACOLOGY, PHYSIOLOGY, PHYTOPATHOLOGY, PSYCHOBIOLOGY, SOCIOBIOLOGY, STRUCTURAL BIOLOGY, VIROLOGY



BIOLOGY COMPRISES AREAS OF STUDY THAT FOCUS ON LIFE AT A VARIETY OF LEVELS AND FROM A DIVERSITY OF PERSPECTIVES

BIOLOGY



Domain - Eukaryota Kingdom - Animalia Phylum - Chordata Vertebrata (Subphylum) Class - Mammalia Order - Primates Anthropoidea (Suborder) Hominoidea (Superfamily) Family - Hominidae Genus - Homo Species - sapiens

LIVING SYSTEMS



HUMANS Lineage (full): root; cellular organisms; Eukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia; Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi; Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini; Hominoidea; Hominidae; Homininae; Homo; Homo sapiens

http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=9606



SPECIES

Defined as a group of living organisms consisting of similar individuals capable of exchanging genes or interbreeding

http://www.nature.com/news/2011/110823/full/news.2011.498.html



NO. OF SPECIES

http://www.iucnredlist.org/documents/summarystatistics/2010_1RL_Stats_Table_1.pdf

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LEVELS OF ORGANISATION

http://www.nature.com/scitable/topicpage/biological-complexity-and-integrative-levels-of-organization-468

15

LEVELS OF ORGANISATION




BIOLOGICAL QUESTIONS

How are all life-forms related? What was the first cell like? How do species adapt to their environment? Which part of our genome is evolving the fastest? Are we descendents of Neanderthals? What genes are responsible for major human disease? Why do we need new flu vaccines every day?

Introduction to Computational Biology, Nello Christiani and Matthew W. Hahn



BIOINFORMATICS ?



COMPUTER SCIENCE [CS]

STUDIES COMPUTABLE PROCESSES AND STRUCTURES ( WITH THE AID OF COMPUTERS )



BIOINFORMATICS AND COMPUTATIONAL BIOLOGY

The boundaries between the two diciplines are not well defined and can be distinguished by the problems they solve

BIOINFORMATICS – is the application of statistics and computer science to the field of molecular biology

COMPUTATIONAL BIOLOGY – actual process of analyzing and interpreting data



DEFINITION OF BIOINFORMATICS

The term bioinformatics was coined in 1978 Bioinformatics is the application of information technology and computer science to the field of molecular biology The science of using / developing computer software and algorithms to record, analyze and merge biologically related data Using computer technology to manage large amounts of biological data Bioinformatics involves the use of techniques including applied mathematics, informatics, statistics, computer science, artificial intelligence, chemistry, and biochemistry to solve biological problems usually on the molecular level http://www.google.com/search?q=define%3ABioinformatics



DEFINITION OF BIOINFORMATICS

The collection, organization, storage, analysis, and integration of large amounts of biological data using networks of computers and databases Bioinformatics involves the integration of computers, software tools, and databases in an effort to address biological questions In summary, the use of computer science to solve biological problems

http://www.google.com/search?q=define%3ABioinformatics

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BIOINFORMATIC FOCUS


ORGANISM

ORGAN

TISSUE CELL

MOLECULES

23

BIOINFORMATIC FOCUS


ORGANISM

ORGAN

TISSUE CELL

MOLECULES

ANALYSIS AND INTERPRETATION OF VARIOUS TYPES OF BIOLOGICAL DATA INCLUDING: NUCLEOTIDE AND AMINO ACID SEQUENCES, PROTEIN DOMAINS, AND PROTEIN STRUCTURES.

Development of new algorithms and statistics with which to assess biological information, such as relationships among members of large data sets.

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BIOINFORMATIC FOCUS

http://www.nature.com/msb/journal/v3/n1/images/msb4100163-f4b.jpg

"Introduction to Bioinformatics" Bioinformatics Course

25

BIOINFORMATIC FOCUS

http://www.jofwidata.com/images/database-design-development.jpg http://wolfson.huji.ac.il/expression/detective.jpg

Development and implementation of tools that enable efficient access and management of different types of information, such as various databases, integrated mapping information


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UNITS OF INFORMATION IN BIOINFORMATICS

DNA Sequence Pathways

RNA Structure Interactions

Protein Evolution Mutations


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UNITS OF INFORMATION IN COMPUTER SCIENCE

File Storage capacity by Bits and Bytes

Bit Byte Kilobyte Megabyte Gigabyte

bit 1 8 1024*8=

8,192 1024*8192=

8,388,608 1024*8388608= 8,589,934,592

byte 8 1 1024 1024*1024=

1,048,576 1024*1048576= 1,073,741,824

Kilobyte 8,192 1024 1 KB 1024 1,048,576

Megabyte 8,388,608 1,048,576 1024 1 MB 1024

Gigabyte 8,589,934,592 1,073,741,824 1,048,576 1024 1 GB

Terabyte 8,796,093,022,208

1TB 1,099,511,627,776 1,073,741,824 1,048,576 1024

Petabyte

9,007,199,254,740,990

1,125,899,906,842,620

1,099,511,627,776

1,073,741,824 1,048,576

1024 TB 1 PB


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File Storage capacity by Bits and Bytes

Bit Byte Kilobyte Megabyte Gigabyte

Petabyte

9,007,199,254,740,990

1,125,899,906,842,620

1,099,511,627,776

1,073,741,824 1,048,576

1024 TB 1 BO

Exabyte

9,223,372,036,854,780,000

1,152,921,504,606,850,000

1,125,899,906,842,620

1,099,511,627,776

1,073,741,824

1,048,576 TB 1024 PB 1 EB

Zettabyte

9,444,732,965,739,290,000,000

1,180,591,620,717,410,000,000

1,152,921,504,606,850,000

1,125,899,906,842,620

1,099,511,627,776

1,073,741,824 TB 1,048,576 PB 1024 EB 1 ZB

Yottabyte

9,671,406,556,917,030,000,000,000

1,208,925,819,614,630,000,000,00

0

1,180,591,620,717,410,000,000 KB

1,152,921,504,606,850,000 MB

1,125,899,906,842,620 GB

1,099,511,627,776 TB 1,073,741,824 PB 1,048,576 EB 1024 ZB 1 YB


UNITS OF INFORMATION IN COMPUTER SCIENCE

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CELL SIZES


http://learn.genetics.utah.edu/content/begin/cells/scale/

http://learn.genetics.utah.edu/content/begin/cells/scale/

30

HUMAN CELL

http://bhavanajagat.files.wordpress.com/2012/02/cell-structure-and-functions.jpg

31

EXAMPLES OF BIOLOGICAL DATA


GENOME – DNA TRANSCRIPTOME – RNA PROTEOME – Proteins

The biological information contained in a genome is encoded in deoxyribonucleic acid (DNA) or, for many types of virus, in ribonucleic acid (RNA)

32

NAME THE NUMBERS


1

3

4 5

2

NUCLEUS DNA GENES CHROMOSOME CELL

33



34

CENTRAL DOGMA OF MOLECULAR BIOLOGY

http://compbio.pbworks.com/f/central_dogma.jpg

DNA is transcribed into RNA and RNA is translated into proteins

35

CENTRAL DOGMA OF MOLECULAR BIOLOGY

http://www.uic.edu/classes/bios/bios100/lectures/centraldogma.jpg

36




The biological information contained in a genome is encoded in deoxyribonucleic acid (DNA) or, for many types of virus, in ribonucleic acid (RNA)

37

GENOME


Is the entirety of an organism’s hereditary information

The genome includes both the genes and non-coding sequences of DNA/RNA

In 1995, Haemophilus influenzae or was the first genome of a living organism to be sequenced in July 1995

1 830 140 base pairs of DNA in single circular chromosome that contains 1740 protein-coding gene, 58 transfer RNA genes and 18 other RNA genes

http://www.sciencemag.org/content/269/5223/local/front-matter.pdf http://en.wikipedia.org/wiki/File:Haemophilus_influenzae_01.jpg

38

WHOLE GENOMES


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GENOME SIZES


Introduction to Computational Biology, Nello Christiani and Matthew W. Hahn

40

GENOME SIZES


Japanese flower Paris japonica 130 billion base pairs – 50 times the human genome

41

COMPLETELY SEQUENCED GENOMES


42

HUMAN GENOME


Human body

• 1014 cells

• (100 trillion)

One cell

• 23 pairs of chromosomes

DNA

• ≈21,000 to 23,000 genes

RNA

• 3 billion pairs of DNA bases

Protein

• ≈100 000 different proteins

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Relative proportions (%) of bases in DNA


CURRENT SCIENCE, VOL. 85, NO. 11, 10 DECEMBER 2003

44

DNA

DNA with high GC-content is more stable than DNA with low GC-content, 3 hydrogen bonds


45

DNA vs RNA

DNA – deoxyribonucleic acid Sugar is deoxyribose DNA is a polymer of deoxyribonucleotides Bases are adenine (A), guanine (G), cytosine (C) and thymine (T)

RNA –ribonucleic acid Sugar is ribose RNA is a polymer of ribonucleotides Bases are adenine (A), guanine (G), cytosine (C) and uracil (U)

http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/Images3/dna_rna1.gif

46

DNA SEQUENCE


Raw DNA sequence Coding or non-coding Parses into genes 4 nucleotide bases ATGC

>ENST00000539570 cdna:known chromosome:GRCh37:15:63889592:63893885:1 gene:ENSG00000259662 gene_biotype:protein_coding transcript_biotype:protein_coding ATGTGGCCACTGCTCACCATGCACATAACCCAGCTCAACCGGGAGTGCCTGCTGCACCTCTTCTCCTTCCTAGACAAGGACAGCAGGAAGAGCCTTGCCAGGACCTGCTCCCAGCTCCACGACGTGTTTGAGGACCCCGCACTCTGGTCCCTGCTGCACTTCCGTTCCCTCACTGAACTCCAGAAGGACAACTTCCTCCTGGGCCCGGCACTCCGCAGCCTCTCCATCTGCTGGCACTCCAGCCGCGTGCAGGTGTGCAGCATTGAGGACTGGCTCAAGAGTGCCTTCCAGAGAAGCATCTGCAGCCGGCACGAGAGCCTGGTCAATGATTTCCTCCTCCGGGTGTGCGACAGGCTTTCTGCTGTGCGCTCCCCACGGAGGCGGGAGGCGCCTGCACCGTCCTCGGGGACTCCGATCGCCGTTGGACCGAAATCACCTCGGTGGGGAGGACCTGACCACTCGGAGTTCGCCGACTTGCGCTCGGGGGTGACGGGGGCCAGGGCTGCCGCGCGCAGGGGTCTGGGGAGCCTCCGGGCGGAGCGACCCAGCGAGACCCCGCCGGCTCCCGGAGTGTCCTGGGGACCGCCACCTCCAGGAGCCCCGGTGGTGATCTCGGTGAAGCAGGAGGAGGGGAAGCAGGGGCGCACGGGCAGAAGGAGCCACCGAGCCGCTCCTCCTTGCGGTTTTGCCCGCACGCGCGTCTGCCCGCCCACCTTTCCTGGGGCGGATGCGTTCCCGCAGTGA

47

A GENE


http://www.down-syndrome.org/updates/2054/updates-2054-figure1-400w.png

48

GENE EXPRESSION REGULATORS


http://www.nature.com/scitable/topicpage/gene-expression-14121669






49

GENE EXPRESSION REGULATORS - EPIGENETICS


http://scienceblogs.com/pharyngula/2008/07/22/epigenetics/

50



GENOME – DNA TRANSCRIPTOME – RNA PROTEOME – Proteins Transcriptome is a set of all RNA molecules including mRNA, rRNA, tRNA, and non-coding RNA produced in one or a population of cells

http://www.bio.miami.edu/~cmallery/150/gene/c7.17.7b.transcription.jpg

51

TRANSCRIPTION


http://www.youtube.com/watch?v=ztPkv7wc3yU

http://www.youtube.com/watch?v=ztPkv7wc3yU

52

TRANSCRIPTION


http://www.bio.miami.edu/~cmallery/150/gene/c7.17.7b.transcription.jpg

53

ALTERNATIVE SPLICING

http://www.nature.com/scitable/content/a-schematic-representation-of-alternative-splicing-95777


54

TYPES OF RNA


http://csls-text.c.u-tokyo.ac.jp/images/fig/fig03_4.gif

mRNA – messenger RNA:

encodes amino acid sequences of a polypeptide

tRNA – transfer RNA: brings

amino acids to ribosomes during translation

rRNA – ribosomal RNA: with

ribosome proteins makes up the ribosomes, the organelles that translate the mRNA

snRNA – small nuclear

RNA: forms complexes with proteins that are used in RNA processing in eukaryotes

55

TYPES OF RNA


http://finchtalk.geospiza.com/2009_05_01_archive.html

56




The proteome is the entire set of proteins expressed by a genome, cell, tissue or organism.

http://artavanis-tsakonas.med.harvard.edu/research_images/figure_harsha_proteome.jpg

57

FROM TRANSCRIPTION TO TRANSLATION


http://www1.cs.columbia.edu/~cleslie/cs4761/microarray/central-dogma.png

58

TRANSLATION


http://0.tqn.com/d/chemistry/1/0/G/m/mrnatranslation.jpg

59

TRANSLATION INITIATION


http://bioap.wikispaces.com/Ch+17+Collaboration

60

TRANSLATION TERMINATION


http://kvhs.nbed.nb.ca/gallant/biology/translation_termination.html

61

UNIVERSAL GENETIC CODE


http://www.biogem.org/codon.jpg

62

AMINO ACIDS

63

PROTEIN

Proteins consists of long chains of amino acid sequences 20 letter alphabet (IUPAC nomenclature)

IUPAC amino acid code

Three letter code

Amino acid

A Ala Alanine

C Cys Cysteine

D Asp Aspartic Acid

E Glu Glutamic Acid

F Phe Phenylalanine

G Gly Glycine

H His Histidine

I Ile Isoleucine

K Lys Lysine

L Leu Leucine

IUPAC amino acid code

Three letter code

Amino acid

M Met Methionine

N Asn Asparagine

P Pro Proline

Q Gln Glutamine

R Arg Arginine

S Ser Serine

T Thr Threonine

V Val Valine

W Trp Tryptophan

Y Tyr Tyrosine


64

PROTEIN SEQUENCE

>sp|P48431|SOX2_HUMAN Transcription factor SOX-2 OS=Homo sapiens GN=SOX2 PE=1 SV=1 MYNMMETELKPPGPQQTSGGGGGNSTAAAAGGNQKNSPDRVKRPMNAFMVWSRGQRRKMA QENPKMHNSEISKRLGAEWKLLSETEKRPFIDEAKRLRALHMKEHPDYKYRPRRKTKTLM KKDKYTLPGGLLAPGGNSMASGVGVGAGLGAGVNQRMDSYAHMNGWSNGSYSMMQDQLGY PQHPGLNAHGAAQMQPMHRYDVSALQYNSMTSSQTYMNGSPTYSMSYSQQGTPGMALGSM GSVVKSEASSSPPVVTSSSHSRAPCQAGDLRDMISMYLPGAEVPEPAAPSRLHMSQHYQS GPVPGTAINGTLPLSHM


65

PROTEIN SIZE

http://www.quora.com/Protein-nutrition-1/Whats-the-average-size-of-a-human-protein-in-kDa

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1150220/

67

PROTEIN STRUCTURE

http://upload.wikimedia.org/wikipedia/commons/thumb/0/05/Protein_structure.png/1024px-Protein_structure.png

68

PROTEIN DOMAINS

69

PROTEIN SEQUENCE

>sp|P48431|SOX2_HUMAN Transcription factor SOX-2 OS=Homo sapiens GN=SOX2 PE=1 SV=1 MYNMMETELKPPGPQQTSGGGGGNSTAAAAGGNQKNSPDRVKRPMNAFMVWSRGQRRKMA QENPKMHNSEISKRLGAEWKLLSETEKRPFIDEAKRLRALHMKEHPDYKYRPRRKTKTLM KKDKYTLPGGLLAPGGNSMASGVGVGAGLGAGVNQRMDSYAHMNGWSNGSYSMMQDQLGY PQHPGLNAHGAAQMQPMHRYDVSALQYNSMTSSQTYMNGSPTYSMSYSQQGTPGMALGSM GSVVKSEASSSPPVVTSSSHSRAPCQAGDLRDMISMYLPGAEVPEPAAPSRLHMSQHYQS GPVPGTAINGTLPLSHM

Proteins are divided into domains

DNA BINDING DOMAIN

http://www.uniprot.org/

70

GENE TRANSCRIPTION, TRANSLATION AND PROTEIN SYNTHESIS

http://compbio.pbworks.com/f/central_dogma.jpg

71

CENTRAL DOGMA

72

BIOINFORMATIC APPLICATIONS


The integrative approaches are useful and applied in Agricultural Higher yield in crops or fruits Disease or drought resistance crops

Medical To understand processes in healthy and disease individuals Genetic diseases

Pharmaceutical To find or develop new and better drugs Gene based drugs Structure based drug designing

73

BIOINFORMATIC QUESTIONS 1


To identify an unknown gene of interest

Sequence matching

Is there a match to known sequence in the database

Which protein family does it match to

How to identify more family members

I have an similar structure, how to identify its potential ligands

How to identify if my gene/protein is found present also in other species

How can I identify genes that are inherited together in a specific region

74



I have to constructed a artificial gene, how do I design the primers, how to check if I have the right sequence?

To know structure of an poorly expressed RNA sequence

To identify the structure and function of a protein sequence

To cluster protein sequences into families of related sequences and develop models

To generate phylogenetic trees to identify the evolutionary relationships using similar proteins/DNA

To identify which other proteins interacts with sequence of interest.

75



Find genes that have similar expression in specific conditions

Find transcription factors that regulate specific genes

Vizualise different gene and protein networks

Describe the regulation of genes

1. introduction to biology and bioinformatics · introduction to biology and bioinformatics...

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