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Primer on Probability Sushmita Roy BMI/CS 576 www.biostat.wisc.edu/bmi576/ Sushmita Roy sroy@biostat.wisc.edu Oct 2nd, 2012 BMI/CS 576

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Definition of probability frequentist interpretation: the probability of an event from a random experiment is the proportion of the time events of same kind will occur in the long run, when the experiment is repeated examples – the probability my flight to Chicago will be on time – the probability this ticket will win the lottery – the probability it will rain tomorrow always a number in the interval [0,1] 0 means never occurs 1 means always occurs

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Sample spaces sample space: a set of possible outcomes for some event event: a subset of sample space examples – flight to Chicago: {on time, late} – lottery: {ticket 1 wins, ticket 2 wins,…,ticket n wins} – weather tomorrow: {rain, not rain} or {sun, rain, snow} or {sun, clouds, rain, snow, sleet} or…

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Random variables random variable: a function associating a value with an attribute of the outcome of an experiment example – X represents the outcome of my flight to Chicago – we write the probability of my flight being on time as P(X = on-time) – or when its clear which variable were referring to, we may use the shorthand P(on-time)

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Notation uppercase letters and capitalized words denote random variables lowercase letters and uncapitalized words denote values well denote a particular value for a variable as follows well also use the shorthand form for Boolean random variables, well use the shorthand

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Probability distributions if X is a random variable, the function given by P(X = x) for each x is the probability distribution of X requirements: sun clouds rain snow sleet 0.2 0.3 0.1

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Joint distributions joint probability distribution: the function given by P(X = x, Y = y) read X equals x and Y equals y example x, y P(X = x, Y = y) sun, on-time 0.20 rain, on-time 0.20 snow, on-time 0.05 sun, late 0.10 rain, late 0.30 snow, late 0.15 probability that its sunny and my flight is on time

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Marginal distributions the marginal distribution of X is defined by the distribution of X ignoring other variables this definition generalizes to more than two variables, e.g.

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Marginal distribution example x, y P(X = x, Y = y) sun, on-time 0.20 rain, on-time 0.20 snow, on-time 0.05 sun, late 0.10 rain, late 0.30 snow, late 0.15 xP(X = x) sun 0.3 rain 0.5 snow 0.2 joint distributionmarginal distribution for X

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Conditional distributions the conditional distribution of X given Y is defined as: the distribution of X given that we know the value of Y

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Conditional distribution example x, y P(X = x, Y = y) sun, on-time 0.20 rain, on-time 0.20 snow, on-time 0.05 sun, late 0.10 rain, late 0.30 snow, late 0.15 xP(X = x|Y=on-time) sun 0.20/0.45 = 0.444 rain 0.20/0.45 = 0.444 snow 0.05/0.45 = 0.111 joint distribution conditional distribution for X given Y=on-time

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Independence two random variables, X and Y, are independent if

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Independence example #1 x, y P(X = x, Y = y) sun, on-time 0.20 rain, on-time 0.20 snow, on-time 0.05 sun, late 0.10 rain, late 0.30 snow, late 0.15 xP(X = x) sun 0.3 rain 0.5 snow 0.2 joint distributionmarginal distributions yP(Y = y) on-time 0.45 late 0.55 Are X and Y independent here?NO.

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Independence example #2 x, y P(X = x, Y = y) sun, fly-United 0.27 rain, fly-United 0.45 snow, fly-United 0.18 sun, fly-Northwest 0.03 rain, fly-Northwest 0.05 snow, fly-Northwest 0.02 xP(X = x) sun 0.3 rain 0.5 snow 0.2 joint distributionmarginal distributions yP(Y = y) fly-United 0.9 fly-Northwest 0.1 Are X and Y independent here?YES.

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two random variables X and Y are conditionally independent given Z if once you know the value of Z, knowing Y doesnt tell you anything about X alternatively Conditional independence

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Conditional independence example FluFeverHeadacheP true 0.04 true false0.04 truefalsetrue0.01 truefalse 0.01 falsetrue 0.009 falsetruefalse0.081 false true0.081 false 0.729 Are Fever and Headache independent? NO.

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Conditional independence example FluFeverHeadacheP true 0.04 true false0.04 truefalsetrue0.01 truefalse 0.01 falsetrue 0.009 falsetruefalse0.081 false true0.081 false 0.729 Are Fever and Headache conditionally independent given Flu : YES.

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Chain rule of probability for two variables for three variables etc. to see that this is true, note that

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Bayes theorem this theorem is extremely useful there are many cases when it is hard to estimate P(x | y) directly, but its not too hard to estimate P(y | x) and P(x)

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Bayes theorem example MDs usually arent good at estimating P(Disorder| Symptom) theyre usually better at estimating P(Symptom | Disorder) if we can estimate P(Fever | Flu) and P(Flu) we can use Bayes Theorem to do diagnosis

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Expected values the expected value of a random variable that takes on numerical values is defined as: this is the same thing as the mean we can also talk about the expected value of a function of a random variable

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Expected value examples Suppose each lottery ticket costs $1 and the winning ticket pays out $100. The probability that a particular ticket is the winning ticket is 0.001.

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distribution over the number of successes in a fixed number n of independent trials (with same probability of success p in each) e.g. the probability of x heads in n coin flips The binomial distribution P(X=x) p=0.5p=0.1 xx

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k possible outcomes on each trial probability p i for outcome x i in each trial distribution over the number of occurrences x i for each outcome in a fixed number n of independent trials e.g. with k=6 (a six-sided die) and n=30 The multinomial distribution vector of outcome occurrences

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Continuous distributions Needed for real-valued attributes – Weight of an object – Height of a tree Pobability distribution needs a probability density function which must be integrated over an interval to derive probability values

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Cumulative distribution function (CDF) To define a probability distribution for a continuous variable, we need to integrate f(x)

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Examples of continuous distributions Uniform distribution over [a,b] Gaussian distribution

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Statistics of alignment scores Q: How do we assess whether an alignment provides good evidence for homology? A: determine how likely it is that such an alignment score would result from chance. What is chance? – real but non-homologous sequences – real sequences shuffled to preserve compositional properties – sequences generated randomly based upon a DNA/protein sequence model

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Model for unrelated sequences well assume that each position in the alignment is sampled randomly from some distribution of amino acids let be the probability of amino acid a the probability of an n -character alignment of x and y is given by

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Model for related sequences well assume that each pair of aligned amino acids evolved from a common ancestor let be the probability that evolution gave rise to amino acid a in one sequence and b in another sequence the probability of an alignment of x and y is given by

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Probabilistic model of alignments How can we decide which possibility (U or R) is more likely? one principled way is to consider the relative likelihood of the two possibilities taking the log, we get

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Probabilistic model of alignments the score for an alignment is thus given by: the substitution matrix score for the pair a, b should thus be given by:

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Scores from random alignments suppose we assume sequence lengths m and n a particular substitution matrix and amino-acid frequencies and we consider generating random sequences of lengths m and n and finding the best alignment of these sequences this will give us a distribution over alignment scores for random pairs of sequences

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The extreme value distribution were picking the best alignments, so we want to know what the distribution of max scores for alignments against a random set of sequences looks like this is given by an extreme value distribution The one that is of most interest to us is called the Gumbel distribution PDF CDF

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x is a given score threshold K and are constants that can be calculated from the substitution matrix the frequencies of the individual amino acids Assessing significance of scores the probability of observing a max score at least x from N random sequence alignments is : Effective lengths of sequences

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Statistics of alignment scores E value in BLAST is the expected number of sequences one would expect to see of max score x – If p is the probability of observing a score > x, E=p*m*n – n is the sum of all sequences in a database. theory for gapped alignments not as well developed computational experiments suggest this analysis holds for gapped alignments (but K and must be estimated from data)

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