Computational Biology, Part 1 Introduction Robert F. Murphy Copyright 1996, 2000, 2001. All rights held.
Slide 2Course Introduction What these courses are about What I expect What you can expect
Slide 3What these courses are about review of routes in which PCs are utilized to take care of issues in science managed learning of illustrative or often utilized projects (03-510) administered learning of programming systems and calculations chose from these utilizations
Slide 4I expect understudies will have essential information of science and science (at the level of Modern Biology/Chemistry) and readiness to take in more understudies will have fundamental nature with utilization of PCs (e.g., at the level of Computing Skills Workshop) and excitement to increase new aptitudes (03-510) understudies make them programme understanding and ability to work to enhance heterogeneous class - I plan to incorporate refreshers on each new point understudies will make inquiries in class and through email
Slide 5You can expect Three noteworthy course segments Sequence Analysis (13 classes) Biological Modeling (11 classes) Biological Imaging (4 classes) Class sessions: addresses/exhibitions/works out/tests Homework assignments 4 homework assignments for 03-311 (80% of review) 8 homework assignments for 03-310 (70% of review) 10 homework assignments for 03-510 (70% of review) Test March 1 (20% for 03-311, 10% for others) Final (20% of review for 03-310, 03-510) Communication on class matters by means of email rundown
Slide 6Textbooks for first 50% obviously For 03-310/311 understudies "Required course book" is Baxevanis & Ouellette For 03-510 understudies "Suggested" course reading is Durbin et al. Extra recommended book Computational Molecular Biology, Peter Clote & Rolf Backofen (ISBN 0-471-87252-0) Chap. 1 is a great prologue to Molec. Biol. for non-Biology majors
Slide 7Specific hotspots for CMU computational science classes Web page ( http://www.bio.cmu.edu/Courses/03310 or 03311 or 03510 ) Lecture Notes (as PowerPoint records) Homework Assignments (as Word documents) Additional materials as required FTP server ( www.bio.cmu.edu ) Files required for homework assignments CompBiol extend volume on AFS/afs/andrew.cmu.edu/usr/murphy/CompBiol
Slide 8Additional classes for 03-510 We will have one extra class meeting for each week for 03-510 for the main portion of the semester just Purpose is to cover some more propelled material and programming assignments
Slide 9Other pertinent courses Second half small scale course " 47-863: Topics in Operations Research: Computational Biology " will be instructed by Dr. R. Ravi Tuesday-Thursday 1:30-2:50 beginning 3/13 Recommended for 03-510 understudies Fall 2001 course on cutting edge points in computational sub-atomic science will be instructed by Dr. Dannie Durand Prerequisite: 03-310/311/510
Slide 10Information stream A noteworthy assignment in computational sub-atomic science is to "interpret" data contained in organic successions Since the nucleotide arrangement of a genome contains all data important to deliver a useful creature, we ought to in principle have the capacity to copy this deciphering utilizing PCs
Slide 11Review of fundamental natural chemistry Central Dogma: DNA makes RNA makes protein Sequence decides structure decides work
Slide 12Structure macromolecular structure partitioned into essential structure (1D grouping) optional structure (nearby 2D & 3D) tertiary structure (worldwide 3D) DNA made out of four nucleotides or "bases": A,C,G,T RNA made out of four likewise: A,C,G,U (T translated as U) proteins are made out of amino acids
Slide 13DNA properties - base organization Some properties of long, actually occuring DNA particles can be anticipated precisely given just the base sythesis , typically communicated as either %GC (the percent of every base match that are G:C), or GC (the mole portion of all bases that are either G or C) %GC = 100* GC
Slide 14DNA properties - liquefying temperature and light thickness Two such properties are T m , the dissolving temperature , characterized as the temperature at which half of the DNA is single-stranded and half is twofold stranded T m ( o C) = 69.3 + 41 GC (for 0.15 M NaCl) 0 , the light thickness , characterized as the thickness of an answer in which a DNA atom will feel no net constrain when centrifuged (the thickness at the point in a thickness slope at which the DNA quits moving, or "groups") 0 (g cm - 3 ) = 1.660 + 0.098 GC (for CsCl)
Slide 15DNA structure - confinement maps Restriction compounds cut DNA at particular successions. A confinement guide is a graphical depiction of the request and lengths of pieces that would be created by the assimilation of a DNA atom with at least one limitation catalysts
Slide 16Restriction guide of a roundabout plasmid with one chemical AccII pGEM4 AccII
Slide 17Restriction guide of all compounds that cut just once AcsI ApoI EcoRI Ecl136II EcoICRI SacI SstI Acc65I Asp718I AvaI SspBI BsrGI Bsp1407I BcoI Cfr9I Eco88I KpnI PspAI XmaI SmaI BamHI BstI XbaI SalI AccI HincII HindII PstI Sse8387I BspMI BbuI PaeI HindIII SphI PvuII SapI NheI NaeI NgoMI NgoAIV SgrAI AflIII Eco47III Aor51HI DsaI BsmFI EcoNI pGEM4 AlwNI AatII SspI XmnI Asp700I AhdI AspEI Eam1105I EclHKI ScaI Eco255I BpmI GsuI BglI XorII PvuI BspCI AviII FspI
Slide 18Transcription interpretation is refined by RNA polymerase RNA polymerase ties to promoters have unmistakable districts "- 35" and "- 10" productivity of translation controlled by official and movement rates translation begin and stop influenced by tertiary structure administrative arrangements can be certain or negative
Slide 19RNA preparing eukaryotic qualities are hindered by introns these are "spliced" out to yield mRNA grafting done by spliceosome joining destinations are very worsen however not all are utilized
Slide 20Translation transformation from RNA to protein is by codon : 3 bases = 1 amino corrosive interpretation done by ribosome interpretation effectiveness controlled by mRNA duplicate number (turnover) and ribosome restricting proficiency interpretation influenced by mRNA tertiary structure
Slide 21Protein limitation pioneer groupings can indicate cell area (e.g., embed crosswise over films) pioneer successions normally evacuated by proteolytic cleavage
Slide 22Postranslational handling peptides crease after interpretation - might be helped or unassisted preparing chemicals perceive particular locales (amino corrosive groupings) protein signs can include auxiliary and tertiary structure, not simply essential structure
Slide 23Goals of Sequence Analysis Assigned Reading: Baxevanis & Ouellette, Chapter 10
Slide 24Goals of Sequence Analysis Management of arrangement data Assembly of grouping sections into finish units (proteins, qualities, chromosomes)
Slide 25Goals of Sequence Analysis Confirmation and forecast of limitation catalyst destinations (for nuc.acids) can help grouping assurance in ranges of instability by allowing testing of particular bases can allow choice of suitable catalysts for succession checking can allow determination of fitting compounds for subcloning or era of tests
Slide 26Goals of Sequence Analysis Finding open perusing outlines (ORFs) for cDNAs or genomic DNA from living beings without introns Finding protein coding areas in DNAs utilizing codon use tables not all ORFs are made into proteins repetition in hereditary code is not completely reflected in the tRNAs made by a specific creature (codon inclination) can use to distinguish "real" coding districts (pseudo-qualities "drift" in their codon utilization) can utilize communicated arrangement labels (ESTs)
Slide 27Goals of Sequence Analysis Finding and utilizing agreement groupings Examples promoters interpretation start destinations interpretation end destinations polyadenylation destinations ribosome restricting destinations protein highlights utilize sets of successions recognized (by different means) as related utilize sets of successions recognized by arrangement correlation
Slide 28Goals of Sequence Analysis Comparison and arrangement of successions contrast grouping with database - objective: find related groupings (SIMILARITY) contrast arrangement with arrangement - objective: find coordinating spaces (ALIGNMENT) contrast database with database - objective: assess hereditary separation (EVOLUTION) either: decide accord successions examinations can be pairwise or various strand
Slide 29Goals of Sequence Analysis Translation to protein grouping and expectation of protein properties - utilize measured penchants of specific amino acids or amino corrosive extends Predict sub-atomic weight Predict isoelectric point (pI) Predict termination coefficient Prediction of optional and tertiary structure RNA - utilize base blending energies protein - utilize affinities
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