Biological Sequence Analysis

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Biological Sequence Analysis

• 140.638.01

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Course Objectives

• See handout

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Related Journals

• Journal of Computational Biology
• PLoS Computational Biology
• Bioinformatics
• Human Molecular Biology
• Nucleic Acid Research
• Nature

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Who are you?

• Field of research/What program
• Stats background
• Computing background
• Register or audit
• Why are you taking this course
• Specific topics you are interested
• Working on any sequence-related projects right
  now

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Administrative Details

• See handout
• Alternative times for class
• Mon 330-5
• Friday 1030-1150

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Historic Overview of Sequence Analysis
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• 1951, Sanger and Tuppy Protein Sequencing
• 1960s, Margaret Dayhoff assembled protein
  sequence atlas. (NBRF)
• Late 1970s, Walter Goad assembled DNA sequence
  database. (LANL)
• Lipman and Benson ENTREZ, internet access to
  sequence database
• Early 1980s, computers applied to sequence
  analysis

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• Sequence Alignment
• 1970, Dot Matrix (Gibbs McIntyre)
• 1970, Dynamic programming for global alignment
  (Needleman Wunsch)
• 1981, local alignment (Smith Waterman)
• 1982-1995, multiple sequence alignment
• Database search for similar sequences
• 1988, Pearson Lipman FASTA
• 1990, Altschul et al. BLAST

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• RNA secondary structure 1971 (Tinoco)
• Gene prediction 1982(Fickett)
• Phylogenetic trees 1987 --
• 2003, Human Genome Project Completed!

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The Human Genome
Genomic Content 3.3billion bases 30K genes 23
chromosomes (22X/Y
DAD
MOM
2 copies in every cell (46 chr) One copy from
each parent Each parent passes on a mixed copy
YOU
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Nucleotides are the chemical building block of
Nucleic Acids DNA and RNA
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Nucleotide sequence determines the amino acid
sequence
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Alternative Splicing

• The human genome contains 30k genes
• But we have gt300k proteins

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The Human Genome
Genomic Content 3.3 billion bases 30K genes 23
chromosomes (22X/Y)
2 copies in every cell One copy from each
parent Each parent passes on a mixed copy
DAD
MOM
Deletions Insertions Mutations Evolutionary Scale
YOU
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Review of basic probability

• Random variables
• Conditional probability
• Expectation variance

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In An Experiment

• Sample Space all conceivable outcomes
• Sample point one conceivable outcome
• Random variable (informal def.) A quantity
  that takes a value from the sample space with
  some degree of randomness
• Event a set of conceivable outcomes
• Probability of an event A how likely will event
  A occur

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Independence

• If A and B are two events defined on the same
  sample space S and
• P(A AND B) P(A) P(B),
• A and B are called independent events.
• Typically, two events are independent if the
  outcome of one does not affect the outcome of the
  other.

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Independent Bernoulli trials

• An event with 2 outcomes (coin-tossing)
• Are the building blocks of
• Binomial distribution
• Geometric distribution

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Expectation of a Random Variable

• The average value of the random variable after a
  large number of random experiments
• Expectation of a Bernoulli random variable, a
  binomial variable?

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Variance of a Random Variable

• The average squared deviation of the random
  variable from its mean
• Variance of a Bernoulli random variable, a
  binomial variable?

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The materials used in this class are made
possible by

• Zhiping Weng, http//zlab.bu.edu
• Carlo Colantuoni
• Wenyi Wang
• Zhijin Wu
• Garland publishing, Albertss the Cell
• And the wealth of internet resources