Statistics

There is a unified interface for computing many types of summary statistics from tree sequences. These are implemented in a flexible way that – like the tree sequence itself – exploits the duality between mutations and branches in the trees to compute statistics of both genome sequence (whose definition does not depend on the trees) and of the underlying trees (whose definition does not depend on the genome sequence). Furthermore, these statistics have a common interface to easily compute (a) averaged statistics in windows along the genome, and (b) summary statistics of many combinations of sets of samples simultaneously. All methods return numpy arrays whose dimensions are determined by the parameters (see Output dimensions).

Please see the tutorial for examples of the statistics API in use.

Warning

Missing data is not currently handled correctly by site statistics defined here, as we always assign missing data to be equal to the ancestral state. Later versions will add this behaviour as an option and will account for the presence of missing data by default.

Available statistics

Here are the statistics that can be computed using tskit, grouped by basic classification and type.

Single site statistics

Patterson’s f statistics

These are the f statistics (also called F statistics) introduced in Reich et al (2009). See the documentation (link below) for the definition, and Peter (2016) for readable discussion of their use.

Y statistics

These are the Y statistics introduced by Ashander et al (2018) as a three-sample intermediate between diversity/divergence (which are pairwise) and Patterson’s f statistics (which are four-way).

Trait correlations

These methods compute correlations and covariances of traits (i.e., an arbitrary vector) with allelic state, possibly in the context of a multivariate linear model with other covariates (as in GWAS).

Derived statistics

The other statistics above all have the property that mode=”branch” and mode=”site” are “dual” in the sense that they are equal, on average, under a high neutral mutation rate. The following statistics do not have this property (since both are ratios of statistics that do have this property).

General methods

These methods allow access to the general method of computing statistics, using weights or sample counts, and summary functions. See the documentation for more details. The pre-implemented statistics above will be faster than using these methods directly, so they should be preferred.

Allele frequency spectrum

We compute allele frequency spectra (AFS), including windowed and joint spectra, using the same general pattern as other statistics, but some of the details about how it is defined, especially in the presence of multiple alleles per site, need to be explained. If all sites are biallelic, then the result is just as you’d expect: see the method documentation at TreeSequence.allele_frequency_spectrum() for the description. Note that with mode="site", we really do tabulate allele counts: if more than one mutation on different parts of the tree produce the same allele, it is the total number with this allele (i.e., inheriting either mutation) that goes into the AFS. The AFS with mode="branch" is the expected value for the Site AFS with infinite-sites, biallelic mutation, so there is nothing surprising there, either.

But, how do we deal with sites at which there are more than two alleles? At each site, we iterate over the distinct alleles at that site, and for each allele, count how many samples in each sample set have inherited that allele. For a concrete example, suppose that we are computing the AFS of a single sample set with 10 samples, and are considering a site with three alleles: a, b, and c, which have been inherited by 6, 3, and 1 samples, respectively, and that allele a is ancestral. What we do at this site depends on if the AFS is polarised or not.

If we are computing the polarised AFS, we add 1 to each entry of the output corresponding to each allele count except the ancestral allele. In our example, we’d add 1 to both AFS[3] and AFS[1]. This means that the sum of all entries of a polarised, site AFS should equal the total number of non-ancestral alleles in the tree sequence that are ancestral to at least one of the samples in the tree sequence but not ancestral to all of them. The reason for this last caveat is that like with most statistics, mutations that are not ancestral to any samples (not just those in the sample sets) are not counted (and so don’t even enter into AFS[0]), and similarly for those alleles inherited by all samples.

Now, if we are computing the unpolarised AFS, we add one half to each entry of the folded output corresponding to each allele count including the ancestral allele. What does this mean? Well, polarised=False means that we cannot distinguish between an allele count of 6 and an allele count of 4. So, folding means that we would add our allele that is seen in 6 samples to AFS[4] instead of AFS[6]. So, in total, we will add 0.5 to each of AFS[4], AFS[3], and AFS[1]. This means that the sum of an unpolarised AFS will be equal to the total number of alleles that are inherited by any of the samples in the tree sequence, divided by two. Why one-half? Well, notice that if in fact the mutation that produced the b allele had instead produced an a allele, so that the site had only two alleles, with frequencies 7 and 3. Then, we would have added 0.5 to AFS[3] twice.

Interface

Tskit offers a powerful and flexible interface for computing population genetic statistics. Consequently, the interface is a little complicated and there are a lot of options. However, we provide sensible defaults for these options and tskit should do what you want in most cases. There are several major options shared by many statistics, which we describe in detail in the following subsections:

Mode

What are we summarising information about?

Windows

What section(s) of the genome are we interested in?

Span normalise

Should the statistic calculated for each window be normalised by the span (i.e. the sequence length) of that window?

The statistics functions are highly efficient and are based where possible on numpy arrays. Each of these statistics will return the results as a numpy array, and the format of this array will depend on the statistic being computed (see the Output format section for details). A convenient feature of the statistics API is that the dimensions of the output array is defined in a simple and intuitive manner by the parameters provided. The Output dimensions section defines the rules that are used.

Please see the tutorial for examples of the statistics API in use.

Mode

There are three modes of statistic: site, branch, and node, that each summarize aspects of the tree sequence in different but related ways. Roughly speaking, these answer the following sorts of question:

site

How many mutations differentiate these two genomes?

branch

How long since these genomes’ common ancestor?

node

On how much of the genome is each node an ancestor of only one of these genomes, but not both?

These three examples can all be answered in the same way with the tree sequence: first, draw all the paths from one genome to the other through the tree sequence (back up to their common ancestor and back down in each marginal tree). Then, (site) count the number of mutations falling on the paths, (branch) measure the length of the paths, or (node) count how often the path goes through each node. There is more discussion of this correspondence in the paper describing these statistics, and precise definitions are given in each statistic.

One important thing to know is that node statistics have somewhat different output. While site and branch statistics naturally return one number for each portion of the genome (and thus incorporates information about many nodes: see below), the node statistics return one number for each node in the tree sequence (and for each window). There can be a lot of nodes in the tree sequence, so beware.

Also remember that in a tree sequence the “sites” are usually just the variant sites, e.g., the sites of the SNPs. (Although tree sequence may in principle have monomorphic sites, those produced by simulation usually don’t.)

Sample sets and indexes

Many standard population genetics statistics are defined with respect to some number of groups of genomes, usually called “populations”. (However, it’s clear from the correspondence to descriptors of tree shape that the definitions can usefully describe something even if the groups of samples don’t come from “separate populations” in some sense.) Basically, statistics defined in terms of sample sets can use the frequency of any allele in each of the sample sets when computing the statistic. For instance, nucleotide divergence is defined for a pair of groups of samples, so if you wanted to compute pairwise divergences between some groups of samples, you’d specify these as your sample_sets. Then, if p[i] is the derived allele frequency in sample set i, under the hood we (essentially) compute the divergence between sample sets i and j by averaging p[i] * (1 - p[j]) + (1 - p[i]) * p[j] across the genome.

So, what if you have samples from each of 10 populations, and want to compute all fourty-five pairwise divergences? You could call divergence fourty-five times, but this would be tedious and also inefficient, because the allele frequencies for one population gets used in computing many of those values. So, statistics that take a sample_sets argument also take an indexes argument, which for a statistic that operates on k sample sets will be a list of k-tuples. If indexes is a length n list of k-tuples, then the output will have n columns, and if indexes[j] is a tuple (i0, ..., ik), then the j-th column will contain values of the statistic computed on (sample_sets[i0], sample_sets[i1], ..., sample_sets[ik]).

How multiple statistics are handled differs slightly between statistics that operate on single sample sets and multiple sample sets.

One-way methods

One-way statistics such as TreeSequence.diversity() are defined over a single sample set. For these methods, sample_sets is interpreted in the following way:

  • If it is a single list of node IDs (e.g., sample_sets=[0, 1 ,2]), this is interpreted as running the calculation over one sample set and we remove the last dimension in the result array as described in the Output dimensions section.

  • If it is None (the default), this is equivalent to sample_sets=ts.samples(), and we therefore compute the statistic over all samples in the tree sequence. Note that we also drop the outer dimension of the result array in this case.

  • If it is a list of lists of samples we return an array for each window in the output, which contains the value of the statistic separately for each of sample_sets in the order they are given.

Multi-way methods

Multi-way statistics such as TreeSequence.divergence() are defined over a k sample sets.

In this case, sample_sets must be a list of lists of sample IDs, and there is no default.

The indexes parameter is interpreted in the following way:

  • If it is a single k-tuple, this is interpreted as computing a single statistic selecting the specified sample sets and we remove the last dimension in the result array as described in the Output dimensions section.

  • If if is None and sample_sets contains exactly k sample sets, this is equivalent to indexes=range(k). Note that we also drop the outer dimension of the result array in this case.

  • If is is a list of k-tuples (each consisting of integers of integers between 0 and len(sample_sets) - 1) of length n we compute n statistics based on these selections of sample sets.

Windows

Each statistic has an argument, windows, which defines a collection of contiguous windows spanning the genome. windows should be a list of n+1 increasing numbers beginning with 0 and ending with the sequence_length. The statistic will be computed separately in each of the n windows, and the k-th row of the output will report the values of the statistic in the k-th window, i.e., from (and including) windows[k] to (but not including) windows[k+1].

Most windowed statistics by default return averages within each of the windows, so the values are comparable between windows, even of different spans. (However, shorter windows may be noisier.) Suppose for instance that you compute some statistic with windows = [0, a, b] for some valid positions 0 < a < b, and get an output array S with two rows. Then, computing the same statistic with windows = [0, b] would be equivalent to averaging the rows of S, obtaining ((a - 0) * S[0] + (b - a) * S[1]) / (b - 0).

There are some shortcuts to other useful options:

windows = None

This is the default and computes statistics in single window over the whole sequence. As the first returned array contains only a single value, we drop this dimension as described in the output dimensions section. Note: if you really do want to have an array with a single value as the result, please use windows = [0.0, ts.sequence_length].

windows = "trees"

This says that you want statistics computed separately on the portion of the genome spanned by each tree, so is equivalent to passing windows = ts.breakpoints(). (Beware: there can be a lot of trees!)

windows = "sites"

This says to output one set of values for each site, and is equivalent to passing windows = [s.position for s in ts.sites()] + [ts.sequence_length]. This will return one statistic for each site (beware!); since the windows are all different sizes you probably want to also pass span_normalise=False (see below).

Span normalise

In addition to windowing there is an option, span_normalise (which defaults to True), All the primary statistics defined here are sums across locations in the genome: something is computed for each position, and these values are added up across all positions in each window. Whether the total span of the window is then taken into account is determined by the option span_normalise: if it is True (the default), the sum for each window is converted into an average, by dividing by the window’s span (i.e. the length of genome that it covers). Otherwise, the sum itself is returned. The default is span_normalise=True, because this makes the values comparable across windows of different sizes. To make this more concrete: pairwise sequence divergence between two samples with mode="site" is the density of sites that differ between the samples; this is computed for each window by counting up the number of sites at which the two differ, and dividing by the total span of the window. If we wanted the number of sites at which the two differed in each window, we’d calculate divergence with span_normalise=False.

Following on from above, suppose we computed the statistic S with windows = [0, a, b] and span_normalise=True, and then computed T in just the same way except with span_normalize=False. Then S[0] would be equal to T[0] / a and S[1] = T[1] / (b - a). Furthermore, the value obtained with windows = [0, b] would be equal to T[0] + T[1]. However, you probably usually want the (default) normalized version: don’t get unnormalised values unless you’re sure that’s what you want. The exception is when computing a site statistic with windows = "sites": this case, computes a statistic with the pattern of genotypes at each site, and normalising would divide these statistics by the distance to the previous variant site (probably not what you want to do).

And, a final note about “span”: in tree sequences produced by msprime coordinates along the sequence are continuous, so the “spans” used here may not correspond to distance along the genome in (say) base pairs. For instance, pairwise sequence divergence is usually a number between 0 and 1 because it is the proportion of bases that differ; this will only be true if the sequence_length, and hence the “spans” are measured in base pairs (which you ensure in msprime by setting recombination and mutation rates equal to the values in units of crossovers and mutations per base pair, respectively).

Output format

Each of the statistics methods returns a numpy ndarray. Suppose that the output is named out. If windows has been specified, the number of rows of the output is equal to the number of windows, so that out.shape[0] is equal to len(windows) - 1 and out[i] is an array of statistics describing the portion of the tree sequence from windows[i] to windows[i + 1] (including the left but not the right endpoint). What is returned within each window depends on the mode:

mode="site" or mode="branch"

The output is a two-dimensional array, with columns corresponding to the different statistics computed: out[i, j] is the j-th statistic in the i-th window.

mode="node"

The output is a three-dimensional array, with the second dimension corresponding to node id. In other words, out.shape[1] is equal to ts.num_nodes, and out[i,j] is an array of statistics computed for node j on the i-th window.

The final dimension of the arrays in other cases is specified by the method.

Note, however, that empty dimensions can optionally be dropped, as described in the Output dimensions section.

A note about default values and division by zero: Under the hood, statistics computation fills in zeros everywhere, then updates these (since statistics are all additive, this makes sense). But now suppose that you’ve got a statistic that returns nan (“not a number”) sometimes, like if you’re taking the diversity of a sample set with only n=1 sample, which involves dividing by n * (n - 1). Usually, you’ll just get nan everywhere that the division by zero happens. But there’s a couple of caveats. For site statistics, any windows without any sites in them never get touched, so they will have a value of 0. For branch statistics, any windows with no branches will similarly remain 0. That said, you should not rely on the specific behavior of whether 0 or nan is returned for “empty” cases like these: it is subject to change.

Output dimensions

In the general case, tskit outputs two dimensional (or three dimensional, in the case of node stats) numpy arrays, as described in the Output format section. The first dimension corresponds to the window along the genome such that for some result array x, x[j] contains information about the jth window. The last dimension corresponds to the statistics being computed, so that x[j, k] is the value of the kth statistic in the jth window (in the two dimensional case). This is a powerful and general interface, but in many cases we will not use this full generality and the extra dimensions in the numpy arrays are inconvenient.

Tskit optionally removes empty dimensions from the output arrays following a few simple rules.

  1. If windows is None we are computing over the single window covering the full sequence. We therefore drop the first dimension of the array.

  2. In one-way stats, if the sample_sets argument is a 1D array we interpret this as specifying a single sample set (and therefore a single statistic), and drop the last dimension of the output array. If sample_sets is None (the default), we use the sample set ts.samples(), invoking this rule (we therefore drop the last dimension by default).

  3. In k-way stats, if the indexes argument is a 1D array of length k we intepret this as specifying a single statistic and drop the last dimension of the array. If indexes is None (the default) and there are k sample sets, we compute the statistic from these sample sets and drop the last dimension.

Rules 2 and 3 can be summarised by “the dimensions of the input determines the dimensions of the output”. Note that dropping these dimensions is optional: it is always possible to keep the full dimensions of the output arrays.

Please see the tutorial for examples of the various output dimension options.

General API

The methods TreeSequence.general_stat() and TreeSequence.sample_count_stat() provide access to the general-purpose algorithm for computing statistics. Here is a bit more discussion of how to use these.

Polarisation

Many statistics calculated from genome sequence treat all alleles on equal footing, as one must without knowledge of the ancestral state and sequence of mutations that produced the data. Separating out the ancestral allele (e.g., as inferred using an outgroup) is known as polarisiation. For instance, in the allele frequency spectrum, a site with alleles at 20% and 80% frequency is no different than another whose alleles are at 80% and 20%, unless we know in each case which allele is ancestral, and so while the unpolarised allele frequency spectrum gives the distribution of frequencies of all alleles, the polarised allele frequency spectrum gives the distribution of frequencies of only derived alleles.

This concept is extended to more general statistics as follows. For site statistics, summary functions are applied to the total weight or number of samples associated with each allele; but if polarised, then the ancestral allele is left out of this sum. For branch or node statistics, summary functions are applied to the total weight or number of samples below, and above each branch or node; if polarised, then only the weight below is used.

Summary functions

For convenience, here are the summary functions used for many of the statistics. Below, \(x\) denotes the number of samples in a sample set below a node, n denotes the total size of a sample set, \(p = x / n\), and boolean expressions (e.g., \((x > 0)\)) are interpreted as 0/1.

diversity

\(f(x) = \frac{x (n - x)}{n (n-1)}\)

For an unpolarized statistic with biallelic loci, this calculates \(2 p (1-p)\).

segregating_sites

\(f(x) = (x > 0) (1 - x / n)\)

(Note: this works because if \(\sum_i p_1 = 1\) then \(\sum_{i=1}^k (1-p_i) = k-1\).)

Y1

\(f(x) = \frac{x (n - x) (n - x - 1)}{n (n-1) (n-2)}\)

divergence

\(f(x_1, x_2) = \frac{x_1 (n_2 - x_2)}{n_1 n_2}\),

unless the two indices are the same, when the diversity function is used.

For an unpolarized statistic with biallelic loci, this calculates \(p_1 (1-p_2) + (1 - p_1) p_2\).

genetic_relatedness

\(f(x_i, x_j) = \frac{1}{2}(x_i - m)(x_j - m)\),

where \(m = \frac{1}{n}\sum_{k=1}^n x_k\) with \(n\) the total number of samples.

Y2

\(f(x_1, x_2) = \frac{x_1 (n_2 - x_2) (n_2 - x_2 - 1)}{n_1 n_2 (n_2 - 1)}\)

f2

\(f(x_1, x_2) = \frac{x_1 (x_1 - 1) (n_2 - x_2) (n_2 - x_2 - 1)}{n_1 (n_1 - 1) n_2 (n_2 - 1)} - \frac{x_1 (n_1 - x_1) (n_2 - x_2) x_2}{n_1 (n_1 - 1) n_2 (n_2 - 1)}\)

For an unpolarized statistic with biallelic loci, this calculates \(((p_1 - p_2)^2 - (p_1 (1-p_2)^2 + (1-p_1) p_2^2)/n_1 - (p_1^2 (1-p_2) + (1-p_1)^2 p_2)/n_2\) \(+ (p_1 p_2 + (1-p_1)(1-p_2))/ n_1 n_2)(1 + \frac{1}{n_1 - 1})(1 + \frac{1}{n_2 - 1})\), which is the unbiased estimator for \((p_1 - p_2)^2\) from a finite sample.

Y3

\(f(x_1, x_2, x_3) = \frac{x_1 (n_2 - x_2) (n_3 - x_3)}{n_1 n_2 n_3}\)

f3

\(f(x_1, x_2, x_3) = \frac{x_1 (x_1 - 1) (n_2 - x_2) (n_3 - x_3)}{n_1 (n_1 - 1) n_2 n_3} - \frac{x_1 (n_1 - x_1) (n_2 - x_2) x_3}{n_1 (n_1 - 1) n_2 n_3}\)

For an unpolarized statistic with biallelic loci, this calculates \(((p_1 - p_2)(p_1 - p_3) - p_1 (1-p_2)(1-p_3)/n_1 - (1-p_1) p_2 p_3/n_1)(1 + \frac{1}{n_1 - 1})\), which is the unbiased estimator for \((p_1 - p_2)(p_1 - p_3)\) from a finite sample.

f4

\(f(x_1, x_2, x_3, x_4) = \frac{x_1 x_3 (n_2 - x_2) (n_4 - x_4)}{n_1 n_2 n_3 n_4} - \frac{x_1 x_4 (n_2 - x_2) (n_3 - x_3)}{n_1 n_2 n_3 n_4}\)

For an unpolarized statistic with biallelic loci, this calculates \((p_1 - p_2)(p_3 - p_4)\).

trait_covariance

\(f(w) = \frac{w^2}{2 (n-1)^2}\),

where \(w\) is the sum of all trait values of the samples below the node.

trait_correlation

\(f(w, x) = \frac{w^2}{2 x (1 - x/n) (n - 1)}\),

where as before \(x\) is the total number of samples below the node, and \(n\) is the total number of samples.

trait_linear_model

\(f(w, z, x) = \frac{1}{2}\left( \frac{w - \sum_{j=1}^k z_j v_j}{x - \sum_{j=1}^k z_j^2} \right)^2\),

where \(w\) and \(x\) are as before, \(z_j\) is the sum of the j-th normalised covariate values below the node, and \(v_j\) is the covariance of the trait with the j-th covariate.