Bio/statistics handout 10:  Binomial and Poisson applications

 

            My purpose in this handout is to provide some examples of how the binomial probability function and the Poisson function arise. 

 

a)  Point statistics:  Suppose that you do an experiment N times and find that a certain even occurs m times out of the N experiments.  Can determine from this data a probability for the event to occur? 

            If we assume that the N experiments are identical in set up, and that the appearance of the even in any one has no bearing on its appearance in any other, then we are let to propose the following hypothesis:  The event occurs in any given experiment with probability q (to be determined) and so the probability that some n ≤ N events occurs in N experiments is given by the q-version of the binomial function, thus

 

Pq(n) =  qn (1-q)N-n .

(10.1)

The question now is:  What value should be used for q?

            The use of experimental data to estimate a single parameter—q in this case—is is an example of what is called point statistics.  Now, it is important for you to realize that there are various ways to obtain a ‘reasonable’ value to use for q.  Here are some:

 

∑       Since we found m events in N trials, take the value of q that gives m for the mean of the probability function in (10.1).  With reference to (9.18) in Handout 9, this choice for q is .

∑       Take q to so that n = m is the integer with the maximal probability.  If you recall (9.20) from Handout 9, this entails taking q so that both

 

 

Pq(m)/ Pq(m+1) > 1    and     Pq(m-1)/ Pq(m) < 1.

(10.2)

      This then implies that  < q < .  Note that q =  satisfies these conditions.

 

b)  P-value and bad choices:  A different approach asks for the bad choices of q rather than the ‘best’ choice.  The business of ruling out various choices for q is more in the spirit of the scientific method.  Moreover, giving the unlikely choices for q is usually much more useful to others than simply giving your favorite candidate.  What follows explains how statisticians determine the likelyhood that a given choice for q is realistic. 

            For this purpose, suppose that we have some preferred value for q.  There is some general agreement that q is not a reasonable choice in the case that there is small probability as computed by the q-version of (10.1) of their being m occurrences of the event of interest.  To make the notion of ‘small probability’ precise, statisticians have introduced the notion of the ‘P-value’ of a measurement.  This is defined with respect to some hypothetical probability function, such as our q-version of (10.1).  In our case, the P-value of m is the probability for the subset of numbers n Î {0, 1, . . . , N} that are at least as far from the mean as is m.  For example, m has P-value  in the case that (10.1) assigns probability  to the set of integers n that obey |n-Nq| ≥ |m-Nq|.  A P-value that is less than 0.05 is deemed ‘significant’ by statisticians.  This is to say that if m has such a P-value, then q is likely to be incorrect.

            In general, the definition of the P-value for a measurement is along the same lines:

 

Definition:  Suppose that a probability function on the set of possible measurements for some experiment is proposed.  The P-value of any given measurement is the probability for the subset of measurements values that lie as far or farther from the mean than the given measurement.  The P-value is deemed significant if it is smaller than 0.05.

 

 

∑n≥m Pq(n) < 0.05 .

(10.3)

            An estimate from the P-value can be had using the Theorem in Section c) of Handout 9.  As you might recall, this theorem invokes the standard deviation, s, as it asserts that the probability of finding a measurement with distance Rs from the mean is less than R-2.  Granted this, a measurement that differs from the mean by 5s or more has probability less than 0.04 and so has a significant P-value.  Such being the case, the 5s bound is often used in lieu of the 0.05 bound.

            To return to our binomial case, to say that m differs from the mean, Nq, by at least 5s, is to say that

 

|m-Nq| ≥ 5 Nq(1-q) .

(10.4)

We should consider q to be a ‘bad’ choice in the case that (10.4) holds.

 

c)  A binomial example using DNA:  As you may recall, a strand of a DNA molecule consists of a chain of smaller molecules tied end to end.  Each small molecule in the chain is one of four types, these labeled A, T, G and C.  Suppose we see that A appears some n times on some length N strand of DNA.  Is this an unusual? 

To make this question precise, we have to decide what is ‘usual’, and this means choosing a probability function for the sample space whose elements consist of all length N strings of letters, where each letter is either A, C, G or T.  For example, the assumption that the appearances of any given molecule on the DNA strand are occurring at random suggests that we take the probability of any given letter A, C, G or T appearing at any given position to be .  Thus, the probability that A does not appear at any given location is , and so the probability that there are n appearances of A in a length N string (if our random model is correct) would be given by the q =  version of the binomial function in equation (10.1). 

This information by itself is not too useful.  A more useful way to measure whether n appearances of A is unusual is to ask for the probability in our standard model for more (or less) appearances of A to occur.  This is to say that if we think that there are too many A’s for the appearance to be random then we should consider the probability as determined by our binomial function  of their being at least this many A’s appearing.  Thus, we should be computing the P-value of the measured number, n.  In the binomial case with q = , this means computing

 

∑kÎB ()k ()N-k

(10.5)

where the sum is over all integers k from the set, B, of integers in {0, . . . , N} that obey |b-| ≥ |n-|. 

            As this sum might be difficult in any given case, we can also resort to using the fact that the probability of being R standard deviations from the mean is less than R-2.  In the case at hand, the standard deviation, s, is (3N)1/2, and so the set of integers b that obey |b-| > R(3N)1/2 has probability less than R-2.  Taking R = 5, we see that our value for n has P-value less that 0.05 if the measured value of n obeys |n-| ≥ 5(3N)1/2.  In this regard, never forget that the P-value is defined with respect to an underlying theoretical proposal for a particular probability function.  Thus, a significant P-value kills the theory.

            Note that our result from the preceding paragraph for this DNA example can be framed as follows:  The measured fraction, , of occurrences of A has significant P value in our random model in the case that

 

| -| >  .

(10.6)

You should note here that as N gets bigger, the right hand side of this last inequality gets smaller.  Thus, as N gets bigger, the experiment must find the ratio  ever closer to  so as to forstall the death of our hypothesis about the random occurrences of the constituent molecules on the DNA strant. 

 

d)  An example using the Poisson function:  All versions of the Poisson probability function are defined on the set À = {0, 1, 2, …}.  As noted in the previous handout, a particular version is determined by a choice of a positive number, t.  The Poisson probability for the given value of t is:

 

Pt(n) =  tn e-t.

(10.7)

Here is a suggested way to think about Pt: 

 

Pt(n) gives the probability of seeing n occurrences of a particular event in any given unit time interval when the occurrences are unrelated and they average t per unit time.

(10.8)

            Here is an example that doesn’t come from Biology but is none-the-less dear to my heart:  I like to go star gazing, and over the years, I have noted an average of 1 meteor per night.  Tonight I go out and see 5 meteors.  Is this unexpected given the hypothesis that the appearance of any two meteors are unrelated?  To test this hypothesis, I should compute the P-value of n = 5 using the t = 1 version of (10.7).  Since the mean of Pt is t, this involves computing

 

(∑m≥5 ) e-1 = 1 – (1 + 1 +  +  + )·e-1

(10.9)

My trusty computer can compute this, and I find that P(5) ≤ 0.004.  Thus, my hypothesis of the unrelated and random occurrence of meteors is unlikely to be true.

            What follows is an example from biology, this very relevant to the theory behind the ‘genetic clocks’ that predict the divergence of modern humans from an African ancestor some 100,000 years ago.  To start the story, there is the notion of a ‘point mutation’ of a DNA molecule.  This occurs when the molecule is copied for reproduction when a cell divides; it involves the change of one letter in one place on the DNA string.  Such changes, cellular typographical errors, occur with very low frequency under non-stressful conditions.  Environmental stresses tend to increase the frequency of such mutations.  In any event, under normal circumstances, the average point mutation rate per site on a DNA strand, per generation has been determined via experiments.  Let m denote the latter.  The average number of point mutations per generation on a segment of DNA with N sites on it is thus mN.  In T ≥ 1 generations, the average number of mutations in this N-site strand is thus mNT. 

            Now, make the following assumptions:

 

∑       The occurrence of any one mutation on the given N-site strand has no bearing on the occurrence of another.

∑       Environmental stresses are no different now than in the past,

∑       The strand in question can be mutated at will with no effect on the organism’s reproductive success.

(10.11)

Granted the latter, the probability of seeing n mutations in T generations on this N-site strand of DNA is given by the t = mNT version of the Poisson probability:

 

(mNT)n e-mNT .

(10.10)

            The genetic clock idea exploits this formula in the following manner:  Suppose that two closely related species diverged from a common ancestor some unknown number of generations in the past.  This is the number we want to estimate.  Call it R.  Today, a comparison of the N site strand of DNA in the two organisms finds that they differ by mutations at n sites.  The observed mutations have arisen over the course of T = 2R generations.  That is, there are R generations worth of mutations in the one species and R in the other, so 2R in all.  We next say that R is a reasonable guess if the t = mN(2R) version of the Poisson function gives n any P-value that is greater than 0.05.   For this purpose, remember that the mean of the t version of the Poisson probability function is t.    

            We might also just look for the values of R that make n within 5 standard deviations of the mean for the t = mN(2R) version of the Poisson probability.  Since the square of the standard deviation of the t version of the Poisson probability function is also t, this is equivlent to the demand that | 2 mNR – n | ≤ 5(2 mNR)1/2.  This last gives the bounds

 

  ≤ R ≤ .

  (10.12)

 

 

Exercises:

 

1.      Define a probability function, P, on {0, 1, 2, …} by setting P(n) = ()n.  What is the P-value of 5?

 

2.      Suppose we lock a monkey in a room with a word processor, come back some hours later and see that the monkey has typed N lower case characters.  Suppose this string of N characters contains consecutive characters that read:

 

professor taubes is a jerk

 

Is this monkey onto something?  Or is this just a chance occurrence? To decide, note that this string has 26 characters.  The monkey’s word processor key board allows 48 lower case characters including the space bar.  Assume that the monkey is typing at random, and give the probability that this string appears in the N-characters.  Estimate (within a power of 10) an upper bound for N below which this string has significant P-value.*

 

* This is not quite the correct question to ask since we would be surprised (or maybe not) by any string that had ‘taubes’ in a derogatory fashion.  True, it is very unlikely that this particular string arises.  Somewhat more likely, some string with ‘taubes’ arises.  In particular, such a string has a reasonable chance when N is on the order of 100 billion.