# Mathematical description of lgpr models

#### Juho Timonen

#### 11th August 2021

    library(lgpr)
    #> Attached lgpr 1.2.4, using rstan 2.26.23. Type ?lgpr to get started.

This vignette describes mathematically the statistical models of `lgpr`. We study the different arguments of the `lgp()` or `create_model()` modeling functions and what parts of the probabilistic model they customize. This is a concise description, and the original publication (Timonen et al. (2021)) has more information about the actual motivation for the used modeling approaches, and the tutorials have code examples.

## 1. Bayesian GP regression

The models in `lgpr` are models for the conditional distribution \[ p(y \mid f(\textbf{x}), \theta_{\text{obs}}), \] of response variable \(y\) given covariates \(\textbf{x}\), where \(\theta_{\text{obs}}\) is a possible parameter of the observation model (like the magnitude of observation noise). The function \(f\) has a Gaussian Process (GP) prior \[ f \sim \mathcal{GP}(0, k\left(\textbf{x}, \textbf{x}' \mid \theta_{\text{GP}})\right), \]

with covariance (kernel) function \(k(\textbf{x}, \textbf{x}' \mid \theta_{\text{GP}})\) that has hyperparameters \(\theta_{\text{GP}}\). In addition to the GP prior for \(f\), there is a parameter prior distribution \(p(\theta)\) for \(\theta = \left\{ \theta_{\text{GP}}, \theta_{\text{obs}} \right\}\). Given \(N\) observations \(\mathcal{D} = \{y_n, \textbf{x}_n\}_{n=1}^N\) the probabilistic models in `lgpr` have the form \[\begin{align} p\left(\theta, \textbf{f}\right) &= p\left(\textbf{f} \mid \theta\right) \cdot p(\theta) & \text{(prior)} \\ p(\textbf{y} \mid \textbf{f}, \theta) &= \prod_{n=1}^N p(y_n \mid f(\textbf{x}_n), \theta_{\text{obs}}) & \text{(likelihood)}, \end{align}\] where \(\textbf{f} = \left[ f(\textbf{x}_1), \ldots, f(\textbf{x}_N) \right]^{\top}\), \(\textbf{y} = \left[y_1, \ldots, y_N\right]^{\top}\). The parameter prior density \(p(\theta)\) is the product of the prior densities of each parameter, and the GP prior means that the prior for \(\textbf{f}\) is the multivariate normal \[\begin{equation} p\left(\textbf{f} \mid \theta\right) = \mathcal{N}\left(\textbf{f} \mid \textbf{0}, \textbf{K} \right), \end{equation}\] where the \(N \times N\) matrix \(\textbf{K}\) has entries \(\{ \textbf{K} \}_{in} = k(\textbf{x}_i, \textbf{x}_n \mid \theta_{\text{GP}})\).

## 2. Connection between lgpr arguments and different model parts

The below table shows which parts of the above mathematical description are affected by which arguments to `lgp()` or `create_model()`. You can read more about them in the documentation of said functions.

Argument | Affected model part
--- | ---
`formula` | \(k(\textbf{x}, \textbf{x}')\)
`data` | \(\mathcal{D}\)
`likelihood` | \(p(y_n \mid f(\textbf{x}_n), \theta_{\text{obs}})\)
`prior` | \(p(\theta)\)
`c_hat` | \(p(y_n \mid f(\textbf{x}_n), \theta_{\text{obs}})\)
`num_trials` | \(\mathcal{D}\)
`options` | \(k(\textbf{x}, \textbf{x}')\)

## 3. The `likelihood` argument and observation models

The terms observation model and likelihood are used to refer to the same formula, i.e. \(p(y_n \mid f(\textbf{x}_n), \theta_{\text{obs}})\), though the former means it as a function of \(\textbf{y}\) and the latter as a function of \(\theta\). There are currently five observation models available and they all involve an inverse link function transformation \[ h_n = g^{-1}\left( f(\textbf{x}_n)+ \hat{c}_n \right) \] where \(g\) is determined by the `likelihood` argument and \(\hat{c}_n\) by the `c_hat` argument. The below table shows what the link function is in different cases, and what parameter the corresponding observation model has.

`likelihood` | Link function \(g\) | Parameter \(\theta_{\text{obs}}\)
--- | --- | ---
`gaussian` | identity | \(\sigma\)
`poisson` | logarithm | -
`nb` | logarithm | \(\phi\)
`binomial` | logit | -
`bb` | logit | \(\gamma\)

- In the Gaussian observation model (`likelihood="gaussian"`), \[ p(y_n \mid f(\textbf{x}_n), \theta_{\text{obs}}) = \mathcal{N}(y_n \mid h_n, \sigma^2) \] \(\theta_{\text{obs}}=\sigma\) is a noise magnitude parameter.

- The Poisson observation model (`likelihood="poisson"`) for count data is \[ y_n \sim \text{Poisson}\left(\lambda_n \right), \] where the rate is \(\lambda_n = h_n\).

- In the negative binomial (`likelihood="nb"`) model, \(\lambda_n\) is gamma-distributed with parameters \[ \begin{cases} \text{shape} &= \phi \\ \text{scale} &= \frac{\phi}{h_n} \end{cases}, \] and \(\phi > 0\) controls overdispersion so that \(\phi \rightarrow \infty\) corresponds to the Poisson model.

- When selecting the binomial or beta-binomial observation model for count data, the number of trials \(\eta_n\), for each \(n=1, \ldots, N\) has to be supplied using the `num_trials` argument. The binomial model (`likelihood="binomial"`) is \[ y_n \sim \text{Binomial}(h_n, \eta_n), \] where the success probability \(\rho_n = h_n\).

- In the beta-binomial model (`likelihood="bb"`), \(\rho_i\) is random so that \[ \rho_n \sim \text{Beta}\left(h_n \cdot \frac{1 - \gamma}{\gamma}, \ (1-h_n) \cdot \frac{1 - \gamma}{\gamma}\right), \] and the parameter \(\gamma \in [0, 1]\) controls overdispersion so that \(\gamma \rightarrow 0\) corresponds to the binomial model.

When using the Gaussian observation model with `sample_f=TRUE` the continuous response \(y\) is normalized to unit variance and zero mean, and \(\hat{c}_n = 0\) for all \(n\) is set. In this case the `c_hat` argument has no effect. With `sample_f = TRUE`, sensible defaults are used. See the documentation of the `c_hat` argument of `lgp()` for exact details and the 5. Model inference section for information about the `sample_f` argument.

## 4. The `formula` argument and kernel functions

### Additive GP regression

The GP models of `lgpr` are additive, so that \[\begin{equation} k(\textbf{x}, \textbf{x}' \mid \theta_{\text{GP}}) = \sum_{j=1}^J \alpha_j^2 k_j(\textbf{x}, \textbf{x}' \mid \theta_{\text{GP}}). \end{equation}\] This is equivalent to saying that we have \(f = f^{(1)} + \ldots + f^{(J)}\) modeled so that each component \(j = 1, \ldots, J\) has a GP prior \[\begin{equation} f^{(j)} \sim \mathcal{GP}\left(0, \alpha_j^2 k_j(\textbf{x}, \textbf{x}' \mid \theta_{\text{GP}}) \right), \end{equation}\] independently from other components.

### Formulas and terms

The number of components \(J\) is equal to the number of terms in your `formula`. Terms are separated by a plus sign. An example formula with three terms could be

    y ~ gp(age) + gp(age)*zs(id) + categ(group)

where `y`, `age`, `id` and `group` have to be columns of `data`. Each formula term defines what the corresponding kernel \(k_j\) will be like, and what covariates and parameters it depends on. Each term adds one \(\alpha\) parameter in the GP parameter vector \(\theta_{\text{GP}}\), and possible additional parameters depending on the term.

### Expressions and kernels

Each term is a product (separated by `*`) of what we call expressions. At this point we are not using standard R formula terminology because terms in `lgpr` are parsed in a custom way. Each expression corresponds to one kernel, and the kernel \(k_j\) is the product of all the kernels in term \(j\). Inside parentheses, each expression must contain the name of one `data` variable, as in `gp(age)`. This determines what variable the kernel depends on. Most of the allowed expressions, their corresponding kernels, and allowed variable types are listed below.

Expression | Corresponding kernel | Allowed variable type
--- | --- | ---
`gp()` | Exponentiated quadratic (EQ) | Continuous
`zs()` | Zero-sum (ZS) | Categorical
`categ()` | Categorical (CAT) | Categorical
`gp_ns()` | Nonstationary (NS) | Continuous
`gp_vm()` | Variance-mask (VM) | Continuous

Continuous covariates should be represented in `data` as `numeric` and categorical covariates as `factor`s. Equations for different kernels are listed here briefly. See Timonen et al. (2021) for more motivation and details about what kind of effects they can model alone and in combinations.

- The EQ kernel is \[ k_{\text{EQ}}(x,x' \mid \theta_{\text{GP}}) = \exp \left( -\frac{(x-x')^2}{2 \ell^2}\right) \] and it has the lengthscale parameter \(\ell\). Each EQ kernel adds one lengthscale parameter to \(\theta_{\text{GP}}\).

- The ZS kernel is \[\begin{equation} k_{\text{ZS}}(z, z') = \begin{cases} 1 \ \ \ \text{ if } z = z' \\ \frac{1}{1 - M} \ \ \ \text{ if } z \neq z' \end{cases} \end{equation}\] where \(M\) is the number of different categories for covariate \(z\).

- The CAT kernel is \[\begin{equation} k_{\text{CAT}}(z, z') = \begin{cases} 1 \ \ \ \text{ if } z = z' \\ 0 \ \ \ \text{ if } z \neq z' \end{cases} \end{equation}\]

- The NS kernel is \[\begin{equation} k_{\text{NS}}(x, x' \mid a, \ell) = k_{\text{EQ}}(\omega_a(x), \omega_a(x') \mid \ell), \end{equation}\] where \(\omega_a: \mathbb{R} \rightarrow ]-1,1[\) is an input warping function \[\begin{equation} \omega_a(x) = 2 \cdot \left(\frac{1}{1 + e^{-a x}} - \frac{1}{2} \right), \end{equation}\] Each NS kernel adds one lengthscale parameter \(\ell\) and one warping steepness parameter \(a\) to \(\theta_{\text{GP}}\).

- The VM kernel is \[\begin{equation} k_{\text{VM}}(x, x' \mid a, \ell) = f^a_{\text{VM}}(x) \cdot f^a_{\text{VM}}(x') \cdot k_{\text{NS}}(x, x' \mid a, \ell), \end{equation}\] where \(f^a_{\text{VM}}(x) = \frac{1}{1 + e^{-a h_2 (x-r)}}\) and \(r = \frac{1}{a} \text{logit}(h_1)\). The parameters \(h_1\) and \(h_2\) are determined by `opt$vm_params[1]` and `opt$vm_params[2]`, respectively, where `opt` is the `options` argument given to `lgp()`. Each VM kernel adds one lengthscale parameter \(\ell\) and one warping steepness parameter \(a\) to \(\theta_{\text{GP}}\).

### Masking missing covariates

All kernels that work with continuous covariates are actually also multiplied by a binary mask (BIN) kernel \(k_{\text{BIN}}(x,x')\) which returns \(0\) if either \(x\) or \(x'\) is missing and \(1\) if they are both available. Missing data should be encoded as `NA` or `NaN` in `data`.

### Heterogeneous effects and covariate uncertainty

There are also the `het()` and `unc()` expressions. They cannot be alone in a term but have to be multiplied by EQ, NS or VM. They are not actually kernels alone but edit the covariate or kernel of their term and add additional parameters. See the tutorials for example use cases and Timonen et al. (2021) for their mathematical definition.

## 5. Model inference

After the model is defined, `lgpr` uses the MCMC methods of Stan to obtain draws from the joint posterior \(p\left(\theta, \textbf{f} \mid \mathcal{D}\right)\) or the marginal posterior of parameters, i.e. \(p\left(\theta \mid \mathcal{D}\right)\). Which one of these is done is determined by the `sample_f` argument of `lgp()` or `create_model()`.

### With sample_f = TRUE

This option is always possible but not recommended with `likelihood = "gaussian"`. The joint posterior that is sampled from is \[\begin{equation} p\left(\theta, \textbf{f} \mid \mathcal{D}\right) \propto p\left(\theta, \textbf{f}\right) \cdot p(\textbf{y} \mid \textbf{f}, \theta) \\ \end{equation}\] and sampling requires evaluating the right-hand side and its gradient thousands of times.

### With sample_f = FALSE

This option is only possible (and is automatically selected by default) if `likelihood = "gaussian"`. This is because \[\begin{equation} p\left(\textbf{y} \mid \theta\right) = \mathcal{N}\left(\textbf{y} \mid \textbf{0}, \textbf{K} + \sigma^2 \textbf{I} \right) \end{equation}\] is analytically available only in this case. The distribution that is sampled from is \[\begin{equation} p\left(\theta \mid \mathcal{D}\right) \propto p\left(\theta\right) \cdot p(\textbf{y} \mid \theta) \\ \end{equation}\] and now sampling requires repeatedly evaluating the right-hand side of this equation and its gradient. This analytical marginalization reduces the MCMC dimension by \(N\) and likely improves sampling efficiency. The conditional posterior \(p\left(\textbf{f} \mid \theta, \mathcal{D}\right)\) also has an analytical form for a fixed \(\theta\), so draws from the marginal posterior \(p\left(\textbf{f} \mid \mathcal{D}\right)\) could be obtained by first drawing \(\theta\) and then \(\textbf{f}\), according to the process \[\begin{align} \theta &\sim p\left(\theta \mid \mathcal{D}\right) \\ \textbf{f} & \sim p\left(\textbf{f} \mid \theta, \mathcal{D}\right). \end{align}\] By combining these, we again have draws from the joint posterior \(p\left(\theta, \textbf{f} \mid \mathcal{D}\right)\), but likely with less computational effort.

## References

Timonen, Juho, Henrik Mannerström, Aki Vehtari, and Harri Lähdesmäki. 2021. “Lgpr: An Interpretable Non-Parametric Method for Inferring Covariate Effects from Longitudinal Data.” Bioinformatics 37 (13): 1860–7.