Bioinformatics. Lecturer: Antinisca Di Marco Tutor: Francesco Gallo

Transcription

1 Bioinformatics Lecturer: Antinisca Di Marco Tutor: Francesco Gallo E mails: nome.cognome@univaq.it For appointment Di Marco: Tuersday :30 p.m. Friday 10:00-11:00 a.m. please ask appointment via

2 Topics Syllabus Biological definitions and concepts (DNA, RNA, microrna, Central dogma, mutations, ) Main biological on-line DB. Data extraction from such systems. Alignment algorithms and substitution matrix. Suffix Tree. Phylogenetic analysis. Algorithms to build Phylogenetic trees. Test and accuracy. Computation models for biological systems modeling. Petri Nets and Hidden Markov Model Technologies and languages: Python, Bio-Python e NEO4J Laboratory

3 Material Some chapter on two books; On line DB manuals (item 1-2 del Syllabus) Selected scienfitic papers (item 5-6 del Syllabus )

4 Exam Project: pratical project to develop together with Biotecnologists that uses the concepts introduced in the course. Oral exam: it includes the project discussion and the presentation of a scientific paper selected from the lecturer. Mid-term exam

5 Lectures Time Thursday 11:00-13:00, Friday 11:00 13:00

6 Course Web Page

7 Introduction to Bioinformatics

8 Bioinformatics Bioinformatics is a multi-disciplinary research field having the objective of understanding biology fenoms and mechanisms. Involved disciplines: biology, biochimics, informatics e statistics. It devises and develops Systems to collect and retrieve biology data. Mathematical and statistical techniques and metods for biology data analysis Computational techniques for the management and analysis of biological data.

9 Bioinformatics In particular, we focus on molecular mechanisms (molecular biology) that constist the basis of the life. We focus on the genetic material evolution (molecular evolution). We study the evolutionary process of DNA, RNA and proteines. Information trasmission -> error -> DNA sequence mutation Single individual mutation. Mutation fixed on the whole population or on a part of it.

10 Bioinfomatics Typically, in bioinformatics the study and the analysis of biological data is comparative and made on nucleotide or molecular sequences. Analysis philogenetics has the objective of study the history of evolution. By building the phylogenetic tree that specifies the most probably history of evolution among species.

11 Bioinformatics

12 Different studies Bioinformatics BioInformatics Algorithms for the management and analysis of biological data (mainly molecular and DNA) e.g., sequences analysis and philogenetics analysis) SYSTEM BIOLOGY Computational (formal) models to describe and analyse biology phenomes to predict specific aspects of the modelled phenoms. Computer graphics techniques to graphically represent behaviors of biology phenome or to identify specific situations (diagnosis). Biomedical applications

13 Molecular Biology Basics

14 Cell Cells are considered the basic units of life in part because they come in discrete and easily recognizable packages It is composed by a set of molecules separated from the context by membranes. It has a metabolism. It reproduces it-self Eukaryotic and prokariotics Virus: no cellular organisms

15 Eukariotic Cells Organisms composed by one or more cells that have a well-differentiated nucleus that contains the majority of cellular DNA, enclosed in a porous envelope formed by two membranes. The DNA is therefore retained in a compartment separated from the rest of the contents of the cell, namely cytoplasm, in which takes place most of the reactions of cell metabolism.

16 Prokaryotic Cell The prokaryotic cells are cells lacking a well-defined nucleus and bounded by the cell membrane. Prokaryotic cells, differently from the eukaryotic ones, do not possess organelles, except for ribosomes, and have a very simple internal structure. Not having the nucleus the DNA is scattered in the cytoplasm. The cellular genome is more simple and is constituted by a single circular DNA molecule, in addition to any autonomous replicons. It absents the nuclear membrane. The cytoplasm containing DNA and ribosomes.

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18 Bio-molecules Macromolecules: DNA RNA Proteins saccharides lipids These molecules define the structural and functional characteristics of cells. Mainly Energetic metabolism Metabolites (small molecules)

19 DNA The deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic information necessary to the biosynthesis of RNA and protein (essential molecules for the development and proper functioning of most living organisms). From a chemical standpoint, DNA is an organic polymer consisting of nucleotide sequences: A adenine, T thymine, guanine G, cytosine C. The process of genetic translation (protein synthesis) is possible only in the presence of an intermediate RNA molecule, which is generated by the process known as transcription.

20 RNA Polymers composed of nucleotide sequences: A adenine, U uracil, guanine G, cytosine C Single-stranded (RNA) The RNA molecules are synthesized through a process known as DNA transcription, where a strand of DNA is copied into the corresponding strand of RNA. There are three common types of RNA in all cellular organisms: mrna (messenger RNA) that contains the information for the synthesis of proteins; rrna (ribosomal RNA), which enters into the structure of the ribosome; trna (transfer RNA) needed for translation in the ribosomes.

21 Proteins The proteins are large biological molecules formed by one or more amino-acid chains - Polymers consisting of amino acids (20 different) The polypeptide chain is the primary structure of the protein Protein function: metabolism, energy, transcription, protein synthesis, transportation, communication, cell cycle,...

22 Central Dogma DNA RNA Protein

23 Central Dogma Transcription and translation are the two main processes linking gene to protein Genes provide the instructions for making specific proteins. The bridge between DNA and protein synthesis is RNA. RNA is chemically similar to DNA, except that it contains ribose as its sugar and substitutes the nitrogenous base uracil for thymine. An RNA molecules almost always consists of a single strand.

24 DNA RNA Protein DNA is TRANSCRIBED to messenger RNA (mrna) mrna carries the message to tranfer RNA (trna) trna is TRANSLATED to an amino acid chain, which makes up proteins

25 In DNA or RNA, the four nucleotide monomers act like the letters of the alphabet to communicate information. The specific sequence of hundreds or thousands of nucleotides in each gene carries the information for the primary structure of a protein (the linear order of the 20 possible amino acids) To get from DNA, written in one chemical language, protein, written in another, requires two major stages, transcription and translation.

26 During transcription, a DNA strand provides a template for the synthesis of a complementary RNA strand. This process is used to synthesize any type of RNA from a DNA template. Transcription of a gene produces a messenger RNA (mrna) molecule. mrna carries the message from the nucleus to the ribosomes During translation, the information contained in the order of nucleotides in mrna is used to determine the aminoacid sequence of a polypeptide. Translation occurs at ribosomes.

27 To summarize, genes program protein synthesis via genetic messenger RNA. The molecular chain of command in a cell is DNA RNA protein. This is referred to as the Central Dogma of Biology

28 Mutazioni: alterazioni dell'informazione codificata nel DNA Sostituzioni: cambiamento di una singola base Inserzioni: aggiunte di nucleotidi Delezioni: rimozioni di nucleotidi

29 Mutazioni in sequenze codificanti Sostituzioni sinonime: non modificano l'amino acido di senso: cambiano un amino acido in uno diverso non-senso: cambiano un amino acido in un codone di stop Inserzioni/Delezioni Con cornice di lettura mantenuta (multipli di tre) Frameshift

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32 Evoluzione nel tempo