Exam Molecular Bioinformatics X3 (1MB330) - 1 March, Page 1 of 6. Skriv svar på varje uppgift på separata blad. Lycka till!!

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1 Exam Molecular Bioinformatics X (MB) - March, - Page of Skriv svar på varje uppgift på separata blad. Lycka till!! Write the answers to each of the questions on separate sheets of paper. ood luck!! ) Sequence alignment Δ Δ T T T Denna matris har räknats fram genom dynamisk programmering. Poängen är + för överensstämmelse och för olika baser. Poängen för luckor (gaps) är - för bildning av ny lucka och ( ) x längd för lucklängd. (Totalt lucklängd för varje lucka). a) Rita upp den sekvensinpassning som räknats fram! p b) Redogör för hur de fyra skuggade elementen i matrisen räknats fram! p

2 Exam Molecular Bioinformatics X (MB) - March, - Page of ) Sequence comparison a) Vid sekvensinpassning av proteiner används substitutionsmatriser som t.ex. BLOSUM. Vilken typ av information är denna matris baserad på? p b) Du har en okänd sekvens och vill söka efter homologer i sekvensdatabaser med PSI-Blast. Varför kan denna metod hitta mer avlägsna släktingar än normal Blast? p ) Hidden Markov models a) onstruct a HMM based on the short amino acid alignment below and estimate all transition and emission probabilities based on the maximum likelihood method. p - - W F R - - W I - - D W V S W L * * * b) In how many ways can the sequence s = ' W ' be generated by this model? p c) What would happen to the sensitivity and selectivity of the model if the background pseudocount method were to be used instead? p

3 Exam Molecular Bioinformatics X (MB) - March, - Page of ) Sequence, structure and function a) Which database would you use to find out the identity of a protein with a database identifier such as bd or exr? What kind of data do you expect to find there? p b) What is the twilight zone (in relation to sequence alignment)? p c) What is a Ramachandran plot? How are Ramachandran plots used in structure validation? p d) Which three characteristics of helical integral membrane proteins can be used to recognise them and to predict their topology based on sequence information alone? p e) You are a respected bioinformatician and you are given the D structure of one of the structural genomics targets (it has no sequence similarity to any well-annotated proteins) by a colleague who is a structural biologist. He would like to know if this structure has been seen before. How would you go about to answer his question? (Be careful, because the results will be published and you don't want to claim a new fold for this structure and be proven wrong three months later by another scientist!) Explain the how, why and what of your approach to your colleague. p f) iven is the following information about two proteins: - The first has E.. number... and TH number... - The second has E.. number... and TH number... What can you tell about their structure and function based only on a comparison of these numbers? an you tell something about their evolutionary relationship (if any)? p

4 Exam Molecular Bioinformatics X (MB) - March, - Page of ) Structure-based drug design a) Vad kan en farmakofor användas till? p b) Nämn tre egenskaper hos en annars potent fosfatashämmare som kan utgöra hinder för att den skall kunna bli ett läkemedel. p ) Structure prediction Det finns olika metoder för veckningsigenkänning (fold recognition). Vad försöker man åstadkomma med dessa metoder? Beskriv kortfattat principerna för de olika huvudtyperna av sådana metoder! p ) Fylogeni a) Är parsimonikriteriet konsistent (motivera)? p b) Det finns flera potentiella felkällor vid fylogenianalyser; en av dessa försöker man få en uppfattning om med hjälp av bootstrap. Frågan är, hur genomförs (i princip) och tolkas en bootstrapanalys i fylogenisammanhang, och vad är det för typ av fel som man försöker skatta? p

5 Exam Molecular Bioinformatics X (MB) - March, - Page of 8) Rough sets molecular biologist is working on the androgen receptor. The aim is to find relationships between patient properties and androgen binding. The selected properties are Sex, External Phenotype (normal/ambiguous external genitalia) and Disease (Partial/Mild/omplete ndrogen Insensitivity Syndrome abbreviated correspondingly PIS, MIS and IS). The decision attribute is the strength of binding between androgen and the androgen receptor. Please do the following rough set computations p : a) Find equivalence classes in the universe defined by the table below. b) Does the decision class form a rough set? If so, why? c) ompute the Boolean discernibility function that expresses how all the decision classes can be discerned from each other, and state its prime implicants. How do you interpret these? d) onsider the following decision rule: If Sex () => ndrogen Binding () ompute the accuracy and coverage of this rule. Is this rule a good rule? Patient Sex External Phenotype Disease ndrogen Binding (Kd) mb PIS B mb MIS Normal IS D Normal IS E Normal IS F mb PIS mb MIS H mb PIS (The ndrogen Receptor ene Mutations Database,

6 Exam Molecular Bioinformatics X (MB) - March, - Page of 9) Microarrays You are the group leader of a breast cancer project. You have access to a large databank containing tissue from tumours from a large number of patients. The objective is to analyze the gene expression specific to breast cancer using microarrays. Please indicate all the steps in the analysis from the design of the experiment to the analysis of the resulting data. Specify which considerations you have to take in each step. p