AFRICAN INSTITUTE FOR MATHEMATICAL SCIENCES(AIMS)

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AFRICAN INSTITUTE FOR MATHEMATICAL SCIENCES(AIMS)

• REVIEW COURSE ON BIOINFORMATICS
• 17 MARCH 4 APRIL, 2008
• LECTURER DELE OLUWADE

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EPILOGUE/CONCLUSION

• In the past 2 weeks or so, we have been
  discussing some of the major topics in the
  emergent field of Bioinformatics.
• Some of the basic definitions in the field have
  been included in the various lecture modules,
  exercises, tutorial questions and assignments.

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• This week, a synthetic summary of the discussions
  in the past 2 weeks shall be presented.
• It is hoped that some of the general and
  particular open problems in the field would
  attract the interest of the class, with a view to
  making substantial contribution to this field
  which touches on human health.

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OUTLINE OF THIS PRESENTATION

• In this lecture module, the following, among
  others would be discussed
• (A) Overview of the Chemical Composition of
  Humans
• (B) Practical illustration of the discussion in
  this course
• (C) Some Fundamental Problems of Bioinformatics
• (D) Relevant Mathematical Computational Tools

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A. CHEMICAL COMPOSITION OF HUMANS

• To say that Bioinfomatics is a wide field is an
  understatement.
• This is not unexpected considering the fact that
  Bioinformatics, as an interdisciplinary
  field,runs across at least 4 fields of study,
  including Biology,Computer Science,Mathematics
  and Statistics.

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• The human genome contains about 3 billion base
  pairs.
• These pairs are arranged into 23 pairs of
  chromosomes.
• A small subset of the long sequence creates the
  c. 20,000 human genes
• Most of these genes code for the proteins which
  determine a persons biochemical makeup
  physical characteristics.

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• The remaining genes, about 98- are noncoding DNA
• In certain sections of the human genome,these
  noncoding DNA contains repeated patterns of 2-5
  nucleotides
• The number of repeats in each sequence varies
  from person to person.

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• For a start
• QUESTION NO 1
• HOW CAN WE EXPLAIN, FOR INSTANCE, THE DIFFERENCE
  IN HEIGHTS OF 2 PERSONS IN THE LIGHT OF WHAT HAVE
  BEEN DISCUSSED IN THIS COURSE ON BIOINFORMATICS?

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HUMAN TRAIT DIFFERENCE

• The difference in height relates to the HMGA2
  gene.
• For tall persons, a C is written in the DNA code
  instead of a T i.e they inherit the
  C-containing copy of the DNA code.
• One copy can add about 0.5 cm in height, two
  copies about 1cm etc

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• QUESTION NO 2
• WHAT HAPPENS WHEN A DNA SAMPLE OF A PERSON IS
  TAKEN FOR THE PURPOSE OF RESOLVING CRIMINAL
  PROBLEMS, PATERNITY PROBLEMS etc?

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Q2 DNA ANALYSIS PROCEDURE

• (i) DNA sample is extracted from a cheek swab OR
  blood OR semen OR hair
• (ii) DNA is isolated from other cellular
  components in the laboratory by a technician or a
  robotic instrument.

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• Extracted DNA passes through a standard method of
  creating many additional copies of a selected
  segment of DNA.
• This method or process is called POLYMERASE CHAIN
  REACTION(PCR)?
• For this process, there are 10 relevant sites in
  the United Kingdom and 13 in the U.S.A these are
  the targets of the PCR method.

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• The database system established in the U.S.A to
  link existing local, state and federal systems is
  knon as the COMBINED DNA INDEX SYSTEM (CODIS)?

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• Then, a genetic analyzer separates the resulting
  10 or 13(as the case may be) DNA fragments, and
  measures the number of repeats in each fragment.
• For instance, repeats may be MICROSATELLITE
  REPEATS or SINGLE-NUCLEOTIDE POLYMORPHISMS

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EXAMPLE OF MICROSATELLITE REPEATS

• GTC GAT CCA CAC ACA CAC ACA CAT CGA
  TTC (a)?
• TCG ATC CAC ACA CAC ACA CAC ACA TCG
  ATT (b)?
• ATC CAC ACA CAC ACA CAC ACA CAC ACA TCG
  (c)?
• NOTE
• The dinucleotide repeat CA is reiterated 8
  times in (a), 9 times in (b) and 12 times in ( c
  ) at different positions in the genome.

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EXAMPLE OF SINGLE-NUCLEOTIDE POLYMORPHISMS

• ACGGGTCGTCGATCCATCGATTCGTAGCTAT
• ACGGGTTGTCGATCCATCGATTCGTAGCTAT
• NOTE
• Single-nucleotide polymorphism(SNP, pronounced
  snip) occurs when the same stretch of DNA
  varies from one copy of a chromosome to another
  by a single nucleotide.

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• For the purpose of forensic analysis, only
  repeats at several positions (called LOCI) on the
  genome are important.
• The number of repeats at each locus is called an
  ALLELE

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• QUESTION 3
• WHAT IS RESPONSIBLE FOR DIFFERENCES BETWEEN HUMAN
  GENOMES AROUND THE WORLD?

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• Research has shown that a lot of differences in
  the genomes of races of the world can be traced
  to single nucleotide polymorphisms (SNP)

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(C) SOME FUNDAMENTAL PROBLEMS OF BIOINFORMATICS

• 1.SEQUENCING AND COMPARISON OF THE GENOMES OF
  DIFFERENT SPECIES
• - This activity involves copying several
  different human genomes many times breaking
  them into millions of small fragments.
• - The sequence of bases of genomes varies from
  individual to individual
• - Any 2 humans have the same complement of
  genes, but different alleles
• - Draft sequencing of the following organisms
  has been completed

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• HUMAN GENOME
• BACTERIAL GENOMES
• YEAST
• NEMATODE
• DROSOPHILA MELANOGASTER, a fruit fly

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• 2. IDENTIFICATION OF THE GENES AND DETERMINATION
  OF THE PROTEINS THEY ENCODE
• - Genes can be identified by methods confined
  to a single genome
• OR
• - by comparative methods which use information
  about one organism to understand another related
  one.

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• 3. UNDERSTANDING OF GENE EXPRESSION
• i.e
• - How do genes and proteins act in concert to
  control cellular processes?
• - Why do different cell types express
  different genes do so at different times?

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• 4. TRACING OF THE EVOLUTIONARY RELATIONSHIPS
  AMONG EXISTING SPECIES THEIR EVOLUTIONARY
  ANCESTORS

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• 5. FINDING A SOLUTION TO THE PROTEIN FOLDING
  PROBLEM
• - i.e Giving the linear sequence of amino
  acids in a protein,what is the 3-dimensional
  structure into which it folds?
• - This is still an unsolved problem.

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• 6. DISCOVERY OF THE ASSOCIATIONS BETWEEN GENE
  MUTATIONS DISEASE
• - Diseases like Huntingtons disease Cystic
  fibrosis are caused by a single mutation
• - Diseases like Diabetes, Cancer Heart
  disease are caused by both genetic
  environmental factors

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• (i) Storing of billions of bases of DNA, RNA and
  protein sequence data in public databases
• - COMPUTER PROGRAMMING
• - DATABASE DESIGN

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D.RELEVANT MATHEMATICAL AND COMPUTATIONAL TOOLS

• (ii) Conversion of laser-scanned traces into
  sequences of As, Cs, Gs and Ts
• - DYNAMIC PROGRAMMING (ALGORITHM)?
• - MACHINE LEARNING
• - FOURIER ANALYSIS

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• (iii) Assembling of millions of fragments into
  large pieces
• - COMBINATORIAL THEORY
• - GRAPH THEORY
• - PROBABILITY THEORY
• - STATISTICS

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• (iv) Identification of new genes from an assembly
  of genome
• - HIDDEN MARKOV MODEL
• - STOCHASTIC CONTEXT-FREE GRAMMARS

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• (v) Comparison of new DNA sequences to those in
  the databases
• - FINITE STATE MACHINES OTHER STRING
  SEARCH ALGORITHMS
• - SEQUENCE ALIGNMENT ALGORITHMS(mainly
  involves DYNAMIC ALGORITHM)?
• - STATISTICAL SCORING

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• (vi) Knowing about the proteins which genes
  encode
• - HIDDEN MARKOV MODEL
• - DATA STUCTURES (for clustering
  phylogenetic tree analysis)

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• (vii) Studying of the Structure function of
  protein
• - CODING THEORY

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REFERENCES

• 1. Ostrander, Elaine A (2007), Genetics and the
  Shape of Dogs, American Scientist, Vol. 95,406
  413
• 2. Karp,Richard M (2002),Mathematical Challenges
  From Genomics and Molecular Biology, Notices of
  the American Mathematical Society, Vol. 49, No.
  5,544-553
• 3. Cole, Simon A (2007),Double Helix Jeopardy,
  IEEE Spectrum, August, 38-43