statistics.ppt

Lecture outline Database searches BLAST FASTA Statistical Significance of Sequence Comparison Results Probability of matching runs Karin-Altschul statistics Extreme value distribution The purpose of sequence alignment Homology Function identification about 70% of the genes of M. jannaschii were assigned a function using sequence similarity (1997) Similarity How much similar do the sequences have to be to infer homology? Two possibilities when similarity is detected: The similarity is by chance They evolved from a common ancestor – hence, have similar functions Measures of similarity Percent identity: 40% similar, 70% similar problems with percent identity? Scoring matrices matching of some amino acids may be more significant than matching of other amino acids PAM matrix in 1970, BLOSUM in 1992 problems? Statistical Significance Goal: to provide a universal measure for inferring homology How different is the result from a random match, or a match between unrelated requences? Given a set of sequences not related to the query (or a set of random sequences), what is the probability of finding a match with the same alignment score by chance? Different statistical measures p-value E-value z-score Statistical significance measures p-value: the probability that at least one sequence will produce the same score by chance E-value: expected number of sequences that will produce same or better score by chance z-score: measures how much standard deviations above the mean of the score distribution Search Significance Scores A search will always return some hits. How can we determine how “unusual” a particular alignment score is? ORF’s Assumptions Assessing significance requires a distribution I have an apple of diameter 5”. Is that unusual? Is a match significant? Match scores for aligning my sequence with random sequences. Depends on: Scoring system Database Sequence to search for Length Composition How do we determine the random sequences? Generating “random” sequences Rand