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WHAT IS BIOINFORMATICS? Daniel Svozil, Laborato informatiky a chemie svozild@vscht.cz http://ich.vscht.cz/~svozil

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Canceled lecture Wed, 4. 3. 2015, lecture is canceled

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Studijn materily http://ich.vscht.cz/~svozil/teaching.html http://ich.vscht.cz/~svozil/teaching.html

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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

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edX www.edx.org Data Analysis for Genomics

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studuj.bioinformatiku.cz

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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

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Extraction of biological knowledge from data DataKnowledge convert data to knowledge generate new hypotheses design new experiments Experimental From public databases

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Omes Genome Transcriptome Proteome Reactome Tissue architectures Cell interactions Sigaling Metabolome Cell Organism 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

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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

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Omics Biological knowledge Medical knowledge Improved health Genomics Transcriptomics Proteomics Metabolomics Interactomics includes Sequencing Microarrays LC/MS NMR Two hybrid measured by these data are High-throughput High-noise To reduce noise Advanced pre-processing techniques Reliable high- throughput information Techniques to analyze high-dimensional data and knowledge bases source: Bios 560R Introduction to Bioinformatics, userwww.service.emory.edu/~tyu8/560R/560R_1.pptx

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Key reasearch in bioinformatics sequence bioinformatics structural bioinformatics systems biology analysis of biological pathways to gain e.g. the understanding of disease processes

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21 st century complex systems Designing (forward-engineering) Understanding (reverse-engineering) Fixing Why is it so complex? Can we make a sense of this complexity? How is it robust? http://yilab.bio.uci.edu/ICSB2007_Tutorial_AM1.htm

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CELL BIOLOGY Daniel Svozil

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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

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Prokaryotes vs. Eukaryotes bacteria 1 bacteria = 1 cell lower organisms Escherichia coli (E. coli) plasma membrane nucleus organelles

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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

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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

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Cell cycle Division of the cell in two exact copies.

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Genetics for Dummies, Tara Robinson homologous chromosomes homologous chromosomes copied

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http://www.bothbrainsandbeauty.com/wp-content/uploads/2009/11/chromosomes.jpg

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Karyotype Genetics for Dummies, Tara Robinson

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Mitosis 2n2n 4n4n 2n2n2n2n diploid (2n) mother cell identical diploid (2n) daughter cells division DNA synthesis

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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)

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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

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DNA The Basis of Life

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DNA Biomacromolecule Consists of repeating units DNA in organism does not usually exist in one piece chromosomes

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Deconstructing DNA http://www.umass.edu/molvis/tutorials/dna/ bases, deoxyribose sugar, phosphate nucleotide Bases are flat stacking pYrimidines C, T puRines A, G

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O3 O5 C3 C5 base sugar Nucleoside

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Nucleotide nucleosides are interconnected by phospohodiester bond nucleotide monophosphate nucleoside

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Bases complement each other. Chargaffs rules amount of G = C amount of A = T

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DNA conformations B-DNA A-DNA Z-DNA B A Z

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Biological role of different DNAs B-DNA canonical DNA predominant A-DNA Conditions of lower humidity, common in crystallographic experiments. However, theyre 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.

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Different sets of DNA nuclear DNA cells 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

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Structure of DNA in the eukaryotic cell DNA in human chromosomes: 3.2 10 9 bp. As were diploid: 6.4 10 9 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

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Chromatin nucleosome

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Nucleosome

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Central dogma of molecular biology Wikipedia

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Molecular Cell Biology, Harvey Lodish