Slide 1. Slide 2. Slide 3. BIOINFORMATIKA doc.dr.gregor Anderluh Oddelek za biologijo, Biotehniška fakulteta, Ljubljana.

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1 Slide 1 BIOINFORMATIKA doc.dr.gregor Anderluh Oddelek za biologijo, Biotehniška fakulteta, Ljubljana gregor.anderluh@bf.uni-lj.si Slide 2 Slide 3 Vihinen M (2001) Biomol. Eng. 18:

2 Slide 4 BIOKEMIJA, MOL. BIOLOGIJA IN VARSTVO OKOLJA biokemijski procesi, encimi OSNOVNI CELIČNI GRADNIKI DNA, beljakovine, zgradba beljakovin, zgradba DNA, razvoj molekularne biologije (PRE-GENOMIKA) high-throughput biologija, določanje nukleotidnega zaporedja DNA genoma (GENOMIKA) BIOINFORMATIKA razvoj računalništva, pomoč pri delu biokemika, podatkovne zbirke (proteini, DNA, 3D strukture), programi POST-GENOMIKA strukturna genomika, funkcionalna genomika, transkriptom, proteom, interaktom, metabolom, integrirane podatkovne zbirke, specializirani strežniki Slide 5 Slide 6

3 Slide 7 Slide 8 KONKRETEN PRIMER Sprememba amoniaka v dušik (denitrifikacija) V nekaj korakih 1. Nitrosomonas (bakterija) spremeni NH 4+ in NH 3 v NO 2-2. Nitrobacter winogradskyi spremeni NO 2- v NO 3 - nitritna oksidoreduktaza NO - 2 NO O 2 3. NO 3- se nato spremeni v O 2 in N 2 N. europaea Uporablja amoniak kot vir energije Lahko razgrajuje tudi nekatere halogenirane organske spojine, npr. trikloretilen, benzen in vinil klorid Slide 9

4 Slide 10 Toksična spojina Netoksična spojina Mikroorganizem (bakterija, alga, gliva...) Encim (protein, beljakovina) Okoljska biotehnologija, Proteinsko inženirstvo Slide 11 The central dogma states that once information has passed into protein it cannot get out again. The transfer of information form nucleic acid to nucleic acid, or from nucleic acid to protein, may be possible, but transfer from protein to protein, or from protein to nucleic acid, is impossible. Information means here the precise determination of sequence, either of basis in the nucleic acid or of amino acid residues in the protein. Francis Crick, 1958 Slide 12 DNA Osnovni gradniki so NUKLEOTIDI Adenin Gvanin Citozin Timidin >gi gb CF CF tac36g08.y1 Hydra EST -IV Hydra magnipapillata cdna 5' similar to TR:Q9Y1U9 Q9Y1U9 EQUINATOXIN IV PRECURSOR. ;, mrna sequence AACTAGCAAAGCAGACGCTGGAGGAGGCGCTGGAATAGCAATTTTAGGAGTATTAGCAAAAGTCGGCGTA GAAGCTGCGTTACAGCAAATTGATAATATTTGGAAAGGAGATGTAGTGAGGTATTGGAAATGCGCTGTAG AAAACAGATCCGATAAAACACTTTATGCTTACGGAACAACTACGGAATCGGGAAGTATGGGTACAGTTTT TGCCGATATTCCCCCTGGAAGCACAGGAATTTTTGTGTGGGAAAAATCTAGAGGAGCTGCAACTGGAGCA AGTGGTGTAGTTCATTATCGTTATGGAGACAAGATACTTAATTTAATGGCATCCATTCCATATGATTGGA ACTTGTATCAATCTTGGGCTAATGCACGAGTTTCGAATGAAAAGGAAAGCTTTTACAACTTGTATAACGG GTTAAATGGTGCGAAACCTGCTACAAGAGGAGGAAACTGGGGCGACGTTGATGGTGCAAAATTTTTTCTT ACTGAAAAAAGTCACGCAGAGTTTAAAGTTATTTTTTCTGGTTAACCAAATGTTGTCAAAAAAATTGTTC TTTTTCTGTAAA Protein Osnovni gradniki so AMINOKISLINE

5 Slide 13 Slide 14 Slide 15 The proteins are among the most complicated and enigmatic substances in Nature and appear to be particularly closely related to all that we call Life. Presentation speech, Nobel prize for Chemistry 1958

6 Slide 16 >SLIT_DROME (P24014): MAAPSRTTLMPPPFRLQLRLLILPILLLLRHDAVHAEPYSGGFGSSAVS SGGLGSVGIHIPGGGVGVITEARCPRVCSCTGLNVDCSHRGLTSVPRKI SADVERLELQGNNLTVIYETDFQRLTKLRMLQLTDNQIHTIERNSFQDL VSLERLDISNNVITTVGRRVFKGAQSLRSLQLDNNQITCLDEHAFKGLV ELEILTLNNNNLTSLPHNIFGGLGRLRALRLSDNPFACDCHLSWLSRFL RSATRLAPYTRCQSPSQLKGQNVADLHDQEFKCSGLTEHAPMECGAENS CPHPCRCADGIVDCREKSLTSVPVTLPDDTTDVRLEQNFITELPPKSFS SFRRLRRIDLSNNNISRIAHDALSGLKQLTTLVLYGNKIKDLPSGVFKG LGSLRLLLLNANEISCIRKDAFRDLHSLSLLSLYDNNIQSLANGTFDAM KSMKTVHLAKNPFICDCNLRWLADYLHKNPIETSGARCESPKRMHRRRI ESLREEKFKCSWGELRMKLSGECRMDSDCPAMCHCEGTTVDCTGRRLKE IPRDIPLHTTELLLNDNELGRISSDGLFGRLPHLVKLELKRNQLTGIEP NAFEGASHIQELQLGENKIKEISNKMFLGLHQLKTLNLYDNQISCVMPG SFEHLNSLTSLNLASNPFNCNCHLAWFAECVRKKSLNGGAARCGAPSKV RDVQIKDLPHSEFKCSSENSEGCLGDGYCPPSCTCTGTVVACSRNQLKE IPRGIPAETSELYLESNEIEQIHYERIRHLRSLTRLDLSNNQITILSNY TFANLTKLSTLIISYNKLQCLQRHALSGLNNLRVVSLHGNRISMLPEGS FEDLKSLTHIALGSNPLYCDCGLKWFSDWIKLDYVEPGIARCAEPEQMK DKLILSTPSSSFVCRGRVRNDILAKCNACFEQPCQNQAQCVALPQREYQ CLCQPGYHGKHCEFMIDACYGNPCRNNATCTVLEEGRFSCQCAPGYTGA RCETNIDDCLGEIKCQNNATCIDGVESYKCECQPGFSGEFCDTKIQFCS PEFNPCANGAKCMDHFTHYSCDCQAGFHGTNCTDNIDDCQNHMCQNGGT CVDGINDYQCRCPDDYTGKYCEGHNMISMMYPQTSPCQNHECKHGVCFQ PNAQGSDYLCRCHPGYTGKWCEYLTSISFVHNNSFVELEPLRTRPEANV TIVFSSAEQNGILMYDGQDAHLAVELFNGRIRVSYDVGNHPVSTMYSFE MVADGKYHAVELLAIKKNFTLRVDRGLARSIINEGSNDYLKLTTPMFLG GLPVDPAQQAYKNWQIRNLTSFKGCMKEVWINHKLVDFGNAQRQQKITP GCALLEGEQQEEEDDEQDFMDETPHIKEEPVDPCLENKCRRGSRCVPNS NARDGYQCKCKHGQRGRYCDQGEGSTEPPTVTAASTCRKEQVREYYTEN DCRSRQPLKYAKCVGGCGNQCCAAKIVRRRKVRMVCSNNRKYIKNLDIV RKCGCTKKCY Slide Struktura α-heliksa in β-ploskev Pauling and Corey (1951) Proc. Natl. Acad. Sci. USA 27, ; Proc. Natl. Acad. Sci. USA 37, Slide 18 The Nobel Prize in Chemistry 1954 Linus Carl Pauling "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances " Pauling has tried this method in his studies of the structure of proteins with which he has been occupied during recent years. To make a direct determination of the structure of a protein by X-ray methods is out of the question for the present, owing to the enormous number of atoms in the molecule. A molecule of the coloured blood constituent hemoglobin, which is a protein, contains for example more than 8,000 atoms. On this basis Pauling deduced some possible structures of the fundamental units in proteins, and the problem was then to examine whether these could explain the X-ray data obtained. It has thus become apparent that one of these structures, the so-called alpha-helix, probably exists in several proteins.

7 Slide Prvo amino kislinsko zaporedje proteina (insulin) Sanger, F., Thompson, E.O.P. and Kitai, R. (1955) Biochem. J. 59, 509 Slide 20 The Nobel Prize in Chemistry 1958 Frederick Sanger "for his work on the structure of proteins, especially that of insulin" Doctor Frederick Sanger. It sometimes happens that an important scientific discovery is made so to say "overnight" - if the time is ripe and the necessary background is there. Yours is not of that kind. The first successful determination of the structure of a protein is the result of many years of persistent and zealous work, in which the final solution of the problem has been approached step by step. You knew when you began to look into the structure of the insulin molecule 15 years ago that the problem was a formidable one. Slide 21 The Nobel Prize in Chemistry 1962 Max Ferdinand Perutz But even if the path was now open for a direct structure determination of haemoglobin and myoglobin, there was still an enormous amount of data to be processed. Myoglobin, the smaller of the two molecules, contains about 2,600 atoms, and the positions of most of these are now known. But for this purpose, Kendrew had to examine 110 crystals and measure the intensities of about 250,000 X-ray reflections. The calculations would not have been practicable if he had not had access to a very large electronic computer. The haemoglobin molecule is four times as large, and its structure is known less thoroughly. In both cases, however, Kendrew and Perutz are currently collecting and processing an even greater number of reflections in order to obtain a more detailed picture. John Cowdery Kendrew "for their studies of the structures of globular proteins"

8 Slide 22 Slide Slide 24 The Nobel Prize in Physiology or Medicine 1962 Francis Harry Compton Crick James Dewey Watson Maurice Hugh Frederick Wilkins "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material" Today no one can really ascertain the consequences of this new exact knowledge of the mechanisms of heredity. We can foresee new possibilities to conquer disease and to gain better knowledge of the interaction of heredity and environment and a greater understanding for the mechanisms of the origin of life. In whatever direction we look we see new vistas. We can, through the discovery by Crick, Watson and Wilkins, to quote John Kendrew, see «the first glimpses of a new world».

9 Slide 25 Slide 26 The Nobel Prize in Physiology or Medicine 1968 Robert W. Holley Har Gobind Khorana Marshall W. Nirenberg "for their interpretation of the genetic code and its function in protein synthesis" Dr. Holley, Dr. Khorana, Dr. Nirenberg. At the end of his Nobel lecture, Edward Tatum in 1958 looked into his crystal ball and tried to predict some of the future developments in molecular biology. He suggested among other things that the solution of the genetic code might come during the lifetime of at least some of the members of his audience. This appeared to be a bold prophecy at that time. In reality it took less than three years before the first letters of the code were deciphered and, because of the ingenuity of you three, the nature of the code and much of its function in protein synthesis were known within less than eight years. Together you have written the most exciting chapter in modern biology. Slide 27

10 Slide 28 The Nobel Prize in Chemistry 1980 Walter Gilbert Frederick Sanger "for their contributions concerning the determination of base sequences in nucleic acids" Sanger is responsible for the first complete determination of the sequence of a DNA molecule. He has established the sequence of the 5375 building blocks in DNA from a bacterial virus called phi-x174. Sequence investigations with the methods of Gilbert and Sanger together with the recombinant-dna technique make excellent tools for continued investigations of the structure and function of the genetic material. Slide Avtomatizacija določanja nukleotidnih zaporedij in uporaba fluorescentnih barvil Leroy Hood in Mike Hunkapiller Slide 30

11 Slide 31 Genomics is the study of an organism's genome and the use of the genes. It deals with the systematic use of genome information, associated with other data, to provide answers in biology, medicine, and industry. Genomics has the potential of offering new therapeutic methods for the treatment of some diseases, as well as new diagnostic methods. Other applications are in the food and agriculture sectors. The major tools and methods related to genomics are bioinformatics, genetic analysis, measurement of gene expression, and determination of gene function. In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). This includes both the genes and the non-coding sequences. The term was first coined, in 1920, by Hans Winkler, Professor of Botany at the University of Hamburg. Wikipedia 1986 revija GENOMICS (Roderick Thomas) Slide 32 Bakteriofag φx174 Mycoplasma genitalium Hemophilus influenzae M. tuberculosis Escherichia coli Saccharomyces cerevisiae Caenorhabditis elegans Drosophila melanogaster Arabidopsis thaliana Človek Število baznih parov Število genov Določen evkariontskih, 243 evbakterijskih, 24 arhebakterijskih KEGG: Kyoto Encyclopedia of Genes and Genomes Slide 33

12 Slide ABI PRISM 3700 DNA Analyzers, Applied Biosystems 800 povezanih Compaq Alpha-based 64-bit postaj, vsaka sposobna več kot 250 bilijonov primerjav zaporedij na uro. Slide 35 BIOINFORMATIKA Vmesnik med biologijo in računalništvom. Matematične, statistične in računalniške metode za reševanje bioloških problemov z uporabo DNA in proteinskih zaporedij in povezane informacije. Organiziranje, analiza in distribucija biološke informacije pri opisovanju in reševanju bioloških problemov. Zbiranje, organiziranje, shranjevanje in iskanje biološke informacije v podatkovnih zbirkah. NI ISKANJE ČLANKOV IN BRSKANJE ZA REVIJAMI!!! Slide 36 RAZVOJ RAČUNALNIŠTVA DO KONCA 90. LET 1969 ARPANET, povezava računalnikov na Stanfordu in UCLA UNIX 1974 povezava omrežij računalnikov v internet, protokol TCP (Transmission Control Protocol) 1975 Microsoft Corporation bitni procesorji 1981 Prvi osebni računalnik na tržišču (IBM), DOS 1983 Zgoščenka (CD ROM) 1984 Macintosh (Apple) 1985 Microsoft Windows 1991 Protokoli, ki omogočijo WWW (CERN) 1993 Pentium 32 bitni procesor 1995 Windows 1995

13 Slide 37 Količina Leto Ninety-nine percent of people don t have an inkling about how fast this revolution is coming. Steve Fodor, president of Affimetrix Slide 38 POPLAVA PODATKOV!!!! GenBank nukleotidna zaporedja baz v zaporedjih- tradicionalne zbirke baz v zaporedjih- WGS zbirka iz več kot organizmov UniProt proteinska zaporedja vpisov, ki predstavljajo aminokislin iz zaporedij iz 9495 organizmov PDB- Protein Data Bank 3D strukture makromolekul struktur (1514 nukleinskih kislin, proteinov, ostalo sladkorji, kompleksi...) Slide 39 >gi sp P02023 HBB_HUMAN HEMOGLOBIN BETA CHAIN MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMG NPVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVL AHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

14 Slide 40 SRPASTOCELIČNA ANEMIJA MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPVK AHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEF TPPVQAAYQKVVAGVANALAHKYH HbB HbS CCT GAG GAG P E E CCT GTG GAG P V E Slide 41 ORTOLOGI rezultat speciacije PARALOGI rezultat podvojitve genov po speciaciji HOMOLOGI Slide MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSH-----G-SAQVKGHGKKVADALTNAVAHVDDMPNA ALPHA1 80 ALPHA2 -MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSH-----G-SAQVKGHGKKVADALTNAVAHVDDMPNA 80 THETA -MALSAEDRALVRALWKKLGSNVGVYTTEALERTFLAFPATKTYFSHLDLSP-----G-SSQVRAHGQKVADALSLAVERLDDLPHA 80 GAMMA MGHFTEEDKATITSLWGKVN--VEDAGGETLGRLLVVYPWTQRFFDSFGNLSSASAIMGNPKVKAHGKKVLTSLGDAIKHLDDLKGT 85 BETA MVHLTPEEKSAVTALWGKVN--VDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGT 85 EPSILON MVHFTAEEKAAVTSLWSKMN--VEEAGGEALGRLLVVYPWTQRFFDSFGNLSSPSAILGNPKVKAHGKKVLTSFGDAIKNMDNLKPA 85 DELTA MVHLTPEEKTAVNALWGKVN--VDAVGGEALGRLLVVYPWTQRFFESFGDLSSPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGT 85 MYOGLOBIN -MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMKASEDLKKHGATVLTALGGILKKKGHHEAE LSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR ALPHA1 142 ALPHA2 LSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR THETA LSALSHLHACQLRVDPASFQLLGHCLLVTLARHYPGDFSPALQASLDKFLSHVISALVSEYR GAMMA FAQLSELHCDKLHVDPENFKLLGNVLVTVLAIHFGKEFTPEVQASWQKMVTGVASALSSRYH BETA FATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH EPSILON FAKLSELHCDKLHVDPENFKLLGNVMVIILATHFGKEFTPEVQAAWQKLVSAVAIALAHKYH DELTA FSQLSELHCDKLHVDPENFRLLGNVLVCVLARNFGKEFTPQMQAAYQKVVAGVANALAHKYH MYOGLOBIN IKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154

15 Slide MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNP- Človek 59 Šimpanz MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPK 60 Zajec MVHLSSEEKSAVTALWGKVNVEEVGGEALGRLLVVYPWTQRFFESFGDLSSANAVMNNPK 60 Zlata ribica -VEWTDAERSAIIGLWGKLNPDELGPQALARCLIVYPWTQRYFATFGNLSSPAAIMGNPK 59 Lastovka -VQWTAEEKQLITGLWGKVNVAECGGEALARLLIVYPWTQRFFASFGNLSSPTAVLGNPK 59 Krokodil -ASFDPHEKQLIGDLWHKVDVAHCGGEALSRMLIVYPWKRRYFENFGDISNAQAIMHNEK VKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFG Človek 119 Šimpanz VKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFG 120 Zajec VKAHGKKVLAAFSEGLSHLDNLKGTFAKLSELHCDKLHVDPENFRLLGNVLVIVLSHHFG 120 Zlata ribica VAAHGRTVMGGLERAIKNMDNIKATYAPLSVMHSEKLHVDPDNFRLLADCITVCAAMKFG 119 Lastovka VQAHGKKVLTSFGEAVKNLDSIKNTFSQLSELHCDKLHVDPENFRLLGDILVVVLAAHFG 119 Krokodil VQAHGKKVLASFGEAVCHLDGIRAHFANLSKLHCEKLHVDPENFKLLGDIIIIVLAAHYP KEFTPPVQAAYQKVVAGVANALAHKYH Človek 146 Šimpanz -KEFTPPVQAAYQKVVAGVANALAHKYH 147 Zajec -KEFTPQVQAAYQKVVAGVANALAHKYH 147 Zlata ribica PSGFNADVQEAWQKFLSVVVSALCRQYH 147 Lastovka -KDFTPDCQAAWQKLVRVVAHALARKYH 146 Krokodil -KDFGLECHAAYQKLVRQVAAALAAEYH 146 Slide 44 Slide 45 primarna zgradba sekundarna zgradba terciarna, kvartarna zgradba nukleotidno zaporedje proteinsko zaporedje motiv domena ATGGTGCACCTGAC TCCTGAGGAGAAG... MVHLTPEEK... M-[VIL]-H-[VIL]- -[ST]-P-E2-K... Podatkovna zbirka primarna GeneBank, EMBL, DDBJ primarna Swiss-Prot, PIR, MIPS sekundarna Prosite, Profiles, Pfam, BLOCKS strukturna PDB, SCOP, CATH

16 Slide 46 KEGG: Kyoto Encyclopedia of Genes and Genomes Release 20.1, December 2001 (plus daily updates) Kyoto Encyclopedia of Genes and Genomes (KEGG) is an effort to computerize current knowledge of molecular and cellular biology in terms of the information pathways that consist of interacting molecules or genes and to provide links from the gene catalogs produced by genome sequencing projects. The KEGG project is undertaken in the Bioinformatics Center, Institute for Chemical Research, Kyoto University with supports from the Ministry of Education, Culture, Sports, Science and Technology and the Japan Society for the Promotion of Science. Slide 47 NCBI- The National Center for Biotechnology Information 1988 Kot del National Library of Medicine Namen: razvoj novih informacijskih tehnologij, ki pomagajo razumeti molekularne in genetske procese 1992 Upravljanje z GenBank Entrez Brskalnik za iskanje po bioloških podatkovnih zbirkah, ki jih ureja NCBI (proteinska zaporedja, nukleotidna zaporedja, gensko mapiranje, OMIM, 3D strukture iz PDB, PubMed) Slide 48

17 Slide 49 BIBLIOGRAFSKE PODATKOVNE ZBIRKE NCBI- tekstovne podatkovne zbirke PubMed OMIM BOOK-SHELF PubMed Central PubMed Na NCBI. Prosto dostopna podatkovna zbirka. Vsebuje citate iz MEDLINE in še dodatno informacijo (nekatere druge revije, ki jih v MEDLINE ni) MEDLINE: vsebuje bibliografsko informacijo 4300 revij iz 70 držav; vsebuje preko 11 mio citatov od 1960 naprej. (OLDMEDLINE ) PubMed Journal Browser- informacija o revijah, iz katerih so članki v PubMed; JournalLinkOutProvider- povezave na spletne strani založnikov, ki imajo revije na spletu; MeSH browser (Medical Subject Heading)- pojmi, ki jih PubMed uporablja za indeksiranje člankov Slide 50 OMIM On-line Mendelian Inheritance in Man Katalog človeških genov in bolezni s katerimi so povezani. (=fenotipski dodatek človeškemu genomu) Ureja dr. Victor A McKusick, John Hopkins University Tekstovna informacija in reference, povezave na podatkovne zbirke znotraj NCBI in ostale. Skupaj opisov ( ) Iskanje s ključnimi besedami Slide 51 ExPASy Expert Protein Analysis System Swiss Institute of bioinformatics (SIB) The ExPASy (Expert Protein Analysis System) proteomics server from the Swiss Institute of Bioinformatics (SIB) is dedicated to molecular biology with an emphasis on data relevant to proteins. Avgust 1993 Appel R.D., Bairoch A., Hochstrasser D.F. A new generation of information retrieval tools for biologists: the example of the ExPASy WWW server. Trends Biochem. Sci. 19: (1994). Podatkovne zbirke: SwissProt TrEMBL PROSITE SWISS 2D-PAGE Programi: Orodja za proteomiko Melanie (analiza 2D gelov) Biochemical Pathways

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19 Slide 55 Slide 56 Slide 57

20 Slide 58 OBLIKA ZAPISA Računalnik vs človek GBFF ASN.1 FASTA(Pearson) najbolj enostaven zapis >P00695 MKALIVLGLVLLSVTVQGKVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYNTRATNYNAGDRS TDYGIFQINSRYWCNDGKTPGAVNACHLSCSALLQDNIADAVACAKRVVRDPQGIRAWVAWRNRCQNRD VRQYVQGCGV >gi ref NP_ lysozyme precursor [Homo sapiens] MKALIVLGLVLLSVTVQGKVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYNTRATNYNAGDRS TDYGIFQINSRYWCNDGKTPGAVNACHLSCSALLQDNIADAVACAKRVVRDPQGIRAWVAWRNRCQNRD VRQYVQGCGV >gi ref NM_ Homo sapiens lysozyme (renal amyloidosis) (LYZ), mrna CTAGCACTCTGACCTAGCAGTCAACATGAAGGCTCTCATTGTTCTGGGGCTTGTCCTCCTTTCTGTTACG GTCCAGGGCAAGGTCTTTGAAAGGTGTGAGTTGGCCAGAACTCTGAAAAGATTGGGAATGGATGGCTACA GGGGAATCAGCCTAGCAAACTGGATGTGTTTGGCCAAATGGGAGAGTGGTTACAACACACGAGCTACAAA CTACAATGCTGGAGACAGAAGCACTGATTATGGGATATTTCAGATCAATAGCCGCTACTGGTGTAATGAT GGCAAAACCCCAGGAGCAGTTAATGCCTGTCATTTATCCTGCAGTGCTTTGCTGCAAGATAACATCGCTG Slide 59 Slide 60

21 Slide 61 Slide 62 Slide 63 Score = 90.9 bits (224), Expect = 1e-18 Identities =55/144 (38%), Positives =84/144 (58%),Gaps =7/144(4%) Beta 4 LTPEEKSAVTALWGKV--NVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPVK 61 L+ E+++ V ALW K+ NV EAL R + +P T+ +F DLS + V+ Theta 3 LSAEDRALVRALWKKLGSNVGVYTTEALERTFLAFPATKTYFSHL-DLSPGSS----QVR 57 Beta 62 AHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKE 121 AHG+KV A S + LD+L + LS LH +L VDP +F+LLG+ L+ LA H+ + Theta 58 AHGQKVADALSLAVERLDDLPHALSALSHLHACQLRVDPASFQLLGHCLLVTLARHYPGD 117 Beta 122 FTPPVQAAYQKVVAGVANALAHKY 145 F+P +QA+ K ++ V +AL +Y Theta 118 FSPALQASLDKFLSHVISALVSEY 141

22 Slide 64 Vihinen M (2001) Biomol. Eng. 18: FUNKCIONALNA GENOMIKA TRANSKRIPTOMIKA PROTEOMIKA INTERAKTOMIKA METABOLOMIKA Slide 65 TRANSKRIPTOM 1991 EST- expressed sequence tags (Venter JC et al. (1991) Science 252: ) Craig J Venter TIGR The Institute for Genomic Research dbest Slide Affimetrix proizvede prve DNA čipe

23 Slide 67 SLIKA TRANSFORMACIJA 1 MATRIKA TRANSFORMACIJA 2 BIOLOŠKI POJAV Slide 68 Slide 69

24 Slide 70 Environmental genome shotgun sequencing of the Sargasso Sea. Venter, J.C. et al Science 304: milijona zaporedij, ki so predstavljala več kot 1.2 milijona novih genov z računalniško analizo so uspeli sestaviti 12 kompletnih bakterijskih genomov. iz podatkov ocenjujejo, da je v vzorcu Sargaškega morja vsaj 1800 bakterijskih vrst in preko povsem novih genov. od teh je pet vrst zastopanih v večjem številu. Slide 71 Katalog vseh genov na zemeljski obli? ersion1/html/main.htm Sargasso samples generated over 1 billion bp of ocean genomes and 1.3 million new genes Sampling from 300 additional sites can provide hundreds of billions of base pairs of DNA sequence and up to 1 billion new genes that will permit cost effective analysis of ocean microbial diversity and environmental impact One time cost for DNA sequencing and database $50-70 Million ($15 million in hand) Slide 72 VIRI Spletna stran o bioinformatiki Literatura Popoln seznam na zgornjih spletnih straneh Attwood TK, Parry-Smith DJ (1999) Introduction to Bioinformatics. Prentice Hall, Harlow, United Kingdom gregor.anderluh@bf.uni-lj.si