WHAT IS
BIOINFORMATICS?
Daniel Svozil, Laboratoř informatiky a chemie
svozild@vscht.cz
http://ich.vscht.cz/~svozil
Canceled lecture
• Wed, 9. 3. 2016, lecture is canceled
Studijní materiály
• http://ich.vscht.cz/~svozil/teaching.html
Coursera
• MOOC
• www.coursera.org
• Bioinformatic Methods I, II
• Bioinformatics: Life Sciences on Your Computer
• Bioinformatics Algorithms 1, 2
• Algorithms, Biology, and Programming for Beginners
• Computational Molecular Evolution
edX
• www.edx.org
• Data Analysis for Genomics
studuj.bioinformatiku.cz
Definition
• NCBI
• Bioinformatics is the field of science in which biology, computer
science, and information technology merge into a single discipline.
The ultimate goal of the field is to enable the discovery of new
biological insights and to create a global perspective from which
unifying principles in biology can be discerned.
• Wikipedia.org
• The application of information technology and statistics to the field
of molecular biology.
• The creation and advancement of databases, algorithms,
computational and statistical techniques, and theory to solve formal
and practical problems arising from the management, analysis and
interpretation of biological data.
http://www.ncbi.nlm.nih.gov/About/primer/bioinformatics.html
Extraction of biological knowledge from data
convert data to knowledge
generate new hypotheses
Experimental
Data
Knowledge
From public
databases
design new experiments
Omes
genome – DNA sequence in an organism
transcriptome – mRNA of an entire organism
proteome – all proteins in an organism
metabolome – all metabolites in an organism
interactome – all molecular interactions in an organism
Organism
Cell
Tissue architectures
Genome
Transcriptome
Proteome
Metabolome
Reactome
Cell interactions
Sigaling
……
Omes and Omics
• Genomics
• Primarily sequences (DNA and RNA)
• Databanks and search algorithms
• Supports studies of molecular evolution
• Proteomics
• Sequences (Protein) and structures
• Mass spectrometry, X-ray crystallography
• Databanks, knowledge bases, visualization
• Functional Genomics (transcriptomics)
• Microarray data
• Databanks, analysis tools, controlled terminologies
• Systems Biology (metabolomics)
• Metabolites and interacting systems (interactomics)
• Graphs, visualization, modeling, networks of entities
“Omics”
includes
Advanced
pre-processing
techniques
Reliable highthroughput
information
Genomics
Transcriptomics
Proteomics
Metabolomics
Interactomics
……
measured by
To reduce noise High-throughput
High-noise
Techniques to analyze
high-dimensional data
and knowledge bases
Sequencing
Microarrays
LC/MS
NMR
Two hybrid
……
these data are
Biological knowledge
Medical knowledge
Improved health
source: Bios 560R Introduction to Bioinformatics, userwww.service.emory.edu/~tyu8/560R/560R_1.pptx
Key reasearch in bioinformatics
• sequence bioinformatics
• structural bioinformatics
• systems biology
• analysis of biological pathways to gain e.g. the understanding of
disease processes
21st century – complex systems
• Designing (forward-engineering)
• Why is it so complex?
• Understanding (reverse-engineering)
• Can we make a sense of this
• Fixing
complexity?
• How is it robust?
http://yilab.bio.uci.edu/ICSB2007_Tutorial_AM1.htm
CELL BIOLOGY
Daniel Svozil
Molecular biology
• Though all aspects of biology can be studied at the
molecular level, molecular biology is usually restricted to
the molecules of genes/gene products/heredity –
molecular genetics
• Experiments in molecular biology are done using model
organisms
• Two classes of organism
• Prokaryotes
• Eukaryotes
Prokaryotes vs. Eukaryotes
• plasma membrane
• nucleus
• organelles
bacteria
• 1 bacteria = 1 cell
• lower organisms
• Escherichia coli (E. coli)
Cells in eukaryotes
• body (somatic) cells
• differentiated into special cell types (brain cells, liver cells …)
• produce by simple cell division – mitosis
• sex cells (gametes)
• egg, sperm
• used for sexual reproduction (only eukaryotes)
• meiosis – reduction of the amount of genetic material
Eukaryotic chromosomes
• Threadlike DNA, carries genes
• Each organism has specific number of chromosomes
• Sex chromosomes (determine gender – XX (female), XY
(male)), autosomal chromosomes
• 46 in human, 2 sex, 44 autosomal
• Come in pairs (two in a pair have the same shape and
same set of genes (but different alleles)), homologs,
diploid
Cell cycle
• Division of the cell in two exact copies.
homologous
chromosomes
homologous
chromosomes copied
Genetics for Dummies, Tara Robinson
http://www.bothbrainsandbeauty.com/wp-content/uploads/2009/11/chromosomes.jpg
Karyotype
Genetics for Dummies, Tara Robinson
Mitosis
2n
diploid (2n) mother cell
DNA synthesis
4n
division
2n
2n
identical diploid (2n) daughter cells
Sexual reproduction
• Egg gets fertilized by sperm. Zygote is cretaed.
• Zygote is diploid (divides by mitosis), thus the gametes
must be haploid!
• In organism with diploid
cells, how do you get
haploid?
• Meiosis (another type of
cell division)
Meiosis
• The result of meiosis is a haploid cell.
• From one parent diploid cell you get four haploid cells. In
addition, homologous chromosomes go through
recombination.
http://www.britannica.com
DNA – The
Basis of Life
DNA
• Biomacromolecule
• Consists of repeating units
• DNA in organism does not usually exist in one piece
• chromosomes
Deconstructing DNA
• http://www.umass.edu/molvis/tutorials/dna/
• bases, deoxyribose sugar, phosphate – nucleotide
• Bases are flat → stacking
• pYrimidines – C, T
• puRines – A, G
Nucleoside
base
O5‘
C5‘
sugar
C3‘
O3‘
Nucleotide
• nucleosides are interconnected by phospohodiester bond
• nucleotide monophosphate
nucleoside
Bases complement each
other.
Chargaffs’ rules
• amount of G = C
• amount of A = T
DNA conformations
A
B
Z
B-DNA
A-DNA
Z-DNA
Biological role of different DNAs
• B-DNA
• canonical DNA
• predominant
• A-DNA
• Conditions of lower humidity, common in crystallographic
experiments. However, they’re artificial.
• In vivo – local conformations induced e.g. by interaction with
proteins.
• Z-DNA
• No definite biological significance found up to now.
• It is commonly believed to provide torsional strain relief
(supercoiling) while DNA transcription occurs.
• The potential to form a Z-DNA structure also correlates with regions
of active transcription.
Different sets of DNA
• nuclear DNA
• cell’s nucleus
• majority of functions cell carries out
• sequencing the genome – scientists mean nuclear DNA
• mitochondrial DNA
• mtDNA
• circular, in human very short (17 kbp) with 37 genes (controling
cellular metabolism)
• all mtDNA comes from mom, no recombination - Mitochondrial Eve
• chloroplast DNA
• cpDNA
• circular and fairly large (120 – 160 kbp), with only 120 genes
• inheritance is either maternal, or paternal
Structure of DNA in the eukaryotic cell
• DNA in human chromosomes: 3.2  109 bp. As we’re diploid:
•
•
•
•
•
•
6.4  109 bp.
0.33 nm per bp  2.1 m in each nucleus, size of the
nucleus: 5-10 m across
DNA is highly compacted. Combination DNA + proteins.
During interphase, when cells are not dividing, the genetic
material exists as a nucleoprotein complex called
chromatin, which is dispersed through much of the nucleus.
Further folding and compaction of chromatin during mitosis
produces the visible metaphase chromosomes.
euchromatin – extended
heterochromatin – condensed
Chromatin
nucleosome
Nucleosome
Central dogma of molecular biology
Wikipedia
Molecular Cell Biology, Harvey Lodish