Introduction to Bioinformatics

Transcription

1 Introduction to Bioinformatics

2 Contents Cell biology Organisms and cells Building blocks of cells How genes encode proteins? Bioinformatics What is bioinformatics? Practical applications Tools and databases 2

3 Cell Biology

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5 Lineage tree of life on earth 5

6 Lineage tree of life on earth Prokaryotes Bacteria Archaebacteria Eukaryotes Plants Animals Fungi 6

7 Prokaryotic cells Single cell organisms Consists of cytosol bounded by the plasma membrane Possesses a cell wall Gram-negative bacteria have a thin cell wall and an outer membrane Gram-positive bacteria have a thick cell wall and no outer membrane DNA is condensed to the cell center and lacks a defined nucleus Ribosomes are found in the DNA-free region Relatively simplified internal organization Some can grow in extreme conditions (temperature, ph, salt concentration) 7

8 Prokaryotic cells 8

9 Eukaryotic cells Single cell (unicellular fungi and protozoans) or multicellular organisms (plants and animals) Both plant cells and fungi possess a cell wall, however are of different compositions Surrounded by a plasma membrane, like the prokaryotes Contains a defined nucleus Structurally more complex: organelles, cytoskeleton Organelles are enclosed compartments separated from the cytoplasm, defined by internal membranes Cytoskeletons are structural proteins giving cell strength and rigidity; can be connected to organelles and provide tracks for organelle movements 9

10 Eukaryotic cells 10

11 Lineage tree of life on earth 11

12 Animal cell structure 12

13 Plant cell structure 13

14 Building blocks of cells Macromolecules Nucleic acids (e.g. DNA, RNA) Proteins (e.g. collagen) Sugars (e.g. glucose, glycogen) Lipids (e.g. cholesterol) Other molecules Water Ions 14

15 Central dogma Genetic information flow: DNA mrna Protein 15

16 Deoxyribonucleic acid (DNA) Contains genetic information arranged in units termed genes In an organism, all cells contain the same DNA content Basic subunits adenine (A) guanine (G) cytosine (C) thymine (T) 16

17 Native DNA is a double helix of complementary antiparallel chains 17

18 DNA is packaged into chromosomes 18

19 The total DNA in the chromosomes of an organism is its genome 19

20 Ribonucleic acid (RNA) Contains genetic information as messenger RNAs (mrna) In an organism, cells contain different types of mrnas Basic subunits adenine (A) guanine (G) cytosine (C) uracil (U) 20

21 Protein Contains genetic information as amino acid sequence Basic subunits are 20 amino acids A protein s amino acid sequence determines its 3D structure, which in turn determines the function of that protein Question: What are essential amino acids? Amino acids that cannot be synthesized by the body cells, therefore have to be included in the diet. Soy bean and corn are rich in essential amino acids 21

22 The genetic code is a triplet code 22

23 How genes encode proteins? Example: Gene X ATG GCT TGT TTA CGA ATT TAG mrna AUG GCU UGU UUA CGA AUU TAG Protein Met Ala Cys Leu Arg Ile * M A C L R I * 23

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25 Bioinformatics

26 What is Bioinformatics? Background Massive explosion in the amount of biological information available due to huge advances in the fields of molecular biology and genomics. What is bioinformatics? Bioinformatics is the application of computer technology to the management, interpretation and analysis of biological data. An interdisciplinary research area that is the interface between the biological and computational sciences. Goals To uncover the wealth of biological information hidden in the mass of data. To provide improvements in research fields such as human health, agriculture, the environment, energy and biotechnology. 26

27 Data generation Large scale sequencing projects Genome sequencing Examples: microbial or human genome sequencing Determine the DNA sequence of an organism Discover genes in the genome using bioinformatics tools EST (Expressed Sequence Tag) sequencing Examples: a specific tissue or cell type from a given organism Determine the mrna sequences found in specific tissue or cell type Determine genes expressed in specific tissue or cell type 27

28 DNA sequencing 28

29 Genome sizes E. coli Arabidopsis Rice Maize Human Genome size (Mb) ,500 3,000 Repetitive DNA - 10% 40% 80% 80% Estimated gene count 4,000 27,000 40,000 45,000 35,000 29

30 Genome sequencing strategies Whole genome shotgun sequencing For genome of relatively small sizes (e.g. bacteria) Break up the genome into small DNA fragments Rely on computer algorithms to assemble the fragments Examples: microbial genomes, Drosophila, Human (Celera) Hierarchical sequencing For genome of large sizes (e.g. human, maize) Break genome into many long pieces Map each long piece onto the chromosome (physical mapping) Select and sequence pieces with minimal overlaps Examples: Rice, Human 30

31 Whole Genome Shotgun Genome cut many times at random 1. Cut genomic DNA cut into pieces 2. Sequence random fragments 3. Put sequence together into one piece relying on computer algorithms 31

32 Hierarchical Sequencing Chr 1, region 1 Chr 1, region 5 Genome 1. Genomic DNA cut into pieces 2. Assign chromosomal location for each DNA fragment 3. Sequence fragments originated from known location 4. Stitch together fragments from each chromosomal location 32

33 Genome facts The order of the nucleotide bases contains the instructions for making an organism. There are 4 types of nucleotide base: A- adenine, T- thymine, C- cytosine, G- guanine. Every three bases codes for an amino acid. There are 20 different amino acids that combined in different ways make different proteins. 33

34 Human genome facts The human genome is composed of more than 3 billion nucleotide bases. Almost all nucleotide bases (99.9%) are exactly the same in all people. Our DNA is 98% identical to chimpanzees. Less than 2% of the genome codes for proteins. The vast majority of the DNA in the genome (>97%) has no known function. The functions remain unknown for over 50% of discovered genes. Chromosome 1 has the most genes (2,968) and chromosome Y has the least (231). If unwound and tied together, the strands of DNA in one cell would stretch 6 feet. The total number of human genes is estimated to be between 30,000-40,

35 A piece of DNA sequence CTCTAGCTATCTTGGTCTCCTACACAGCCTATGCACATGAGCCCATGCCTCTCCTCTCCTTGCGCCTGCA TAGAGAGGTGGTATGATCACCTGGAAAGTTTTTAACTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTT ACAAGCCTAGACCTTATGCATGGTCGGACGGACACATCTGATCATAGGACATATGAGTAGGCCACACTCC TCCTGCCCCTCTCTCGTAGAGATCAACACACACTGCTCTTAGTGCCAGGACCTAGAGAGGGGAGCGTGGA GAGGGCATCAGGGGGCCTTGGAGTCCCATCAGTAAAGCACATGTTTCCTTTCTGTGATTCCTCAAGCCCC ATGGACTTACCGCTTTACCAACAACTGCAGCTAAGCCCGTCTTCCCCAAAGACGGACCAATCCAGCAGCT TCTACTGCTACCCATGCTCCCCTCCCTTCGCCGCCGCCGACGCCAGCTTTCCCCTCAGCTACCAGATCGG TAGTGCCGCGGCCGCCGACGCCACCCCTCCACAAGCCGTGATCAACTCGCCGGACCTGCCGGTGCAGGCG CTGATGGACCACGCGCCGGCGCCGGCTACAGAGCTGGGCGCCTGCGCCAGTGGTGCAGAAGGATCCGGCG CCAGCCTCGACAGGGCGGCTGCCGCGGCGAGGAAAGACCGGCACAGCAAGATATGCACCGCCGGCGGGAT GAGGGACCGCCGGATGCGGCTCTCCCTTGACGTCGCGCGCAAATTCTTCGCGCTGCAGGACATGCTTGGC TTCGACAAGGCAAGCAAGACGGTACAGTGGCTCCTCAACACGTCCAAGTCCGCCATCCAGGAGATCATGG CCGACGACGCGTCTTCGGAGTGCGTGGAGGACGGCTCCAGCAGCCTCTCCGTCGACGGCAAGCACAACCC GGCAGAGCAGCTGGGAGGAGGAGGAGATCAGAAGCCCAAGGGTAATTGCCGCGGCGAGGGGAAGAAGCCG GCCAAGGCAAGTAAAGCGGCGGCCACCCCGAAGCCGCCAAGAAAATCGGCCAATAACGCACACCAGGTCC CCGACAAGGAGACGAGGGCGAAAGCGAGGGAGAGGGCGAGGGAGCGGACCAAGGAGAAGCACCGGATGCG CTGGGTAAAGCTTGCTTCAGCAATTGACGTGGAGGCGGCGGCTGCCTCGGGGCCGAGCGACAGGCCGAGC TCGAACAATTTGAGCCACCACTCATCGTTGTCCATGAACATGCCGTGTGCTGCCGCTGAATTGGAGGAGA GGGAGAGGTGTTCATCAGCTCTCAGCAATAGATCAGCAGGTAGGATGCAAGAAATCACAGGGGCGAGCGA CGTGGTCCTGGGCTTTGGCAACGGAGGAGGAGGATACGGCGACGGCGGCGGCAACTACTACTGCCAAGAG CAATGGGAACTCGGTGGAGTCGTCTTTCAGCAGAACTCACGCTTCTACTGAACACTACGGGCGCACTAGG TACTAGAACTACTCTTTCGACTTACATCTATCTCCTTTCCCTCAACGTGAGCTTCTCAATAATTTGCTGT CTTAATCTATGCGTGTGTTTCTCTTTCTAGACTTCGTAATTGGCTGTGTGACGATGAACT 35

36 A piece of DNA sequence - carrying a gene unit CTCTAGCTATCTTGGTCTCCTACACAGCCTATGCACATGAGCCCATGCCTCTCCTCTCCTTGCGCCTGCA TAGAGAGGTGGTATGATCACCTGGAAAGTTTTTAACTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTT ACAAGCCTAGACCTTATGCATGGTCGGACGGACACATCTGATCATAGGACATATGAGTAGGCCACACTCC TCCTGCCCCTCTCTCGTAGAGATCAACACACACTGCTCTTAGTGCCAGGACCTAGAGAGGGGAGCGTGGA GAGGGCATCAGGGGGCCTTGGAGTCCCATCAGTAAAGCACATGTTTCCTTTCTGTGATTCCTCAAGCCCC ATGGACTTACCGCTTTACCAACAACTGCAGCTAAGCCCGTCTTCCCCAAAGACGGACCAATCCAGCAGCT TCTACTGCTACCCATGCTCCCCTCCCTTCGCCGCCGCCGACGCCAGCTTTCCCCTCAGCTACCAGATCGG TAGTGCCGCGGCCGCCGACGCCACCCCTCCACAAGCCGTGATCAACTCGCCGGACCTGCCGGTGCAGGCG CTGATGGACCACGCGCCGGCGCCGGCTACAGAGCTGGGCGCCTGCGCCAGTGGTGCAGAAGGATCCGGCG CCAGCCTCGACAGGGCGGCTGCCGCGGCGAGGAAAGACCGGCACAGCAAGATATGCACCGCCGGCGGGAT GAGGGACCGCCGGATGCGGCTCTCCCTTGACGTCGCGCGCAAATTCTTCGCGCTGCAGGACATGCTTGGC TTCGACAAGGCAAGCAAGACGGTACAGTGGCTCCTCAACACGTCCAAGTCCGCCATCCAGGAGATCATGG CCGACGACGCGTCTTCGGAGTGCGTGGAGGACGGCTCCAGCAGCCTCTCCGTCGACGGCAAGCACAACCC GGCAGAGCAGCTGGGAGGAGGAGGAGATCAGAAGCCCAAGGGTAATTGCCGCGGCGAGGGGAAGAAGCCG GCCAAGGCAAGTAAAGCGGCGGCCACCCCGAAGCCGCCAAGAAAATCGGCCAATAACGCACACCAGGTCC CCGACAAGGAGACGAGGGCGAAAGCGAGGGAGAGGGCGAGGGAGCGGACCAAGGAGAAGCACCGGATGCG CTGGGTAAAGCTTGCTTCAGCAATTGACGTGGAGGCGGCGGCTGCCTCGGGGCCGAGCGACAGGCCGAGC TCGAACAATTTGAGCCACCACTCATCGTTGTCCATGAACATGCCGTGTGCTGCCGCTGAATTGGAGGAGA GGGAGAGGTGTTCATCAGCTCTCAGCAATAGATCAGCAGGTAGGATGCAAGAAATCACAGGGGCGAGCGA CGTGGTCCTGGGCTTTGGCAACGGAGGAGGAGGATACGGCGACGGCGGCGGCAACTACTACTGCCAAGAG CAATGGGAACTCGGTGGAGTCGTCTTTCAGCAGAACTCACGCTTCTACTGAACACTACGGGCGCACTAGG TACTAGAACTACTCTTTCGACTTACATCTATCTCCTTTCCCTCAACGTGAGCTTCTCAATAATTTGCTGT CTTAATCTATGCGTGTGTTTCTCTTTCTAGACTTCGTAATTGGCTGTGTGACGATGAACT 36

37 Data analysis (tools) Sequence properties Length, base composition, GC content, etc. Sequence assembly Put sequence together based on similarity Gene prediction Find gene units in a given DNA sequence Repeat finding Find repeated units in a given DNA sequence Sequence similarity search Find other similar sequences based on DNA or protein sequences Protein function analysis Predict protein function based on known functional units found in protein sequence (domains) 37

38 Data storage (databases) Databases Research articles What is the latest research with regard to genes involved in horse coat color? Taxonomy How many plant or animal genomes have been sequenced? Nucleotide What is the nucleotide sequence of the maize domestication gene teosinte branched 1 (tb1)? Protein What is the protein sequence of the maize domestication gene tb1? Genome Where are the human diabetes genes located in the human genome? Which chromosome? 38

39 Long term goals Agriculture Improve insect resistance Improve nutritional quality Improve drought resistant and/or environmental adaptability Animals Improve production and nutrition of farm animals Molecular medicine Preventative medicine Gene therapy Microbial genome Waste cleanup Climate change Alternative energy sources Biotechnology Antibiotic resistance Forensic analysis of microbes Metagenomics 39