Note

Click here to download the full example code

# Kernel tricks¶

This example shows some niche, but useful functionalities of `cellrank.tl.kernels.Kernel`

.

CellRank is split into `cellrank.tl.kernels`

and `cellrank.tl.estimators`

. Kernels compute transition matrices
based on some inputs, like RNA velocity [Bergen20], [Manno18], while estimators perform inference based on a given
kernel, e.g. they compute initial and terminal cells and fate probabilities.

Here, will will dive a bit deeper into the how these kernel objects work.

```
import cellrank as cr
adata = cr.datasets.pancreas_preprocessed("../example.h5ad")
adata
```

Out:

```
AnnData object with n_obs × n_vars = 2531 × 2000
obs: 'day', 'proliferation', 'G2M_score', 'S_score', 'phase', 'clusters_coarse', 'clusters', 'clusters_fine', 'louvain_Alpha', 'louvain_Beta', 'initial_size_unspliced', 'initial_size_spliced', 'initial_size', 'n_counts', 'velocity_self_transition', 'dpt_pseudotime'
var: 'highly_variable_genes', 'gene_count_corr', 'means', 'dispersions', 'dispersions_norm', 'fit_r2', 'fit_alpha', 'fit_beta', 'fit_gamma', 'fit_t_', 'fit_scaling', 'fit_std_u', 'fit_std_s', 'fit_likelihood', 'fit_u0', 'fit_s0', 'fit_pval_steady', 'fit_steady_u', 'fit_steady_s', 'fit_variance', 'fit_alignment_scaling', 'velocity_genes'
uns: 'clusters_colors', 'clusters_fine_colors', 'diffmap_evals', 'iroot', 'louvain_Alpha_colors', 'louvain_Beta_colors', 'neighbors', 'pca', 'recover_dynamics', 'velocity_graph', 'velocity_graph_neg', 'velocity_params'
obsm: 'X_diffmap', 'X_pca', 'X_umap', 'velocity_umap'
varm: 'PCs', 'loss'
layers: 'Ms', 'Mu', 'fit_t', 'fit_tau', 'fit_tau_', 'spliced', 'unspliced', 'velocity', 'velocity_u'
obsp: 'connectivities', 'distances'
```

First, we create some kernels which will be used to compute the cell-to-cell transition matrix:

`cellrank.tl.kernels.ConnectivityKernel`

computes the transition matrix using the KNN graph from`scanpy.pp.neighbors()`

[Wolf18]. Note that this kernel is by itself directionless and should be used in conjunction with e.g.`cellrank.tl.kernels.VelocityKernel`

.`cellrank.tl.kernels.VelocityKernel`

uses RNA velocity for the transition matrix computation [Manno18] [Bergen20], but can also take into account uncertainty in RNA velocity.`cellrank.tl.kernels.PseudotimeKernel`

works similarly as in Palantir [Setty19] - it orients the edges of the KNN graph constructed in the expression space using the pseudotemporal ordering of cells, such as Diffusion Pseudotime (DPT) [Haghverdi16].

```
ck = cr.tl.kernels.ConnectivityKernel(adata)
vk = cr.tl.kernels.VelocityKernel(adata)
pk = cr.tl.kernels.PseudotimeKernel(adata)
```

Kernels can be easily combined with each other. All of the constants within parentheses (if they are needed) will be normalized to 1 automatically. This effect will be shown after the transition matrix has been computed.

```
10 * vk + 15 * ck
```

Out:

```
((10 * <VelocityKernel>) + (15 * <ConnectivityKernel>))
```

We can also build more complex kernel expression. Note that multiple usage of the same kernel instance in the expression caches it’s transition matrix, so it’s only computed once.

```
k = ((vk + vk + 42 * vk) + ck * 2) + ck * (3 * vk + 4 * pk)
k
```

Out:

```
((1 * ((1 * <VelocityKernel>) + (1 * <VelocityKernel>) + (42 * <VelocityKernel>) + (2 * <ConnectivityKernel>))) + ((1 * <ConnectivityKernel>) * (1 * ((3 * <VelocityKernel>) + (4 * <PseudotimeKernel>)))))
```

For complex expression like the one above, one can get the unique base kernels as follows.

```
k.kernels
```

Out:

```
[<VelocityKernel>, <ConnectivityKernel>, <PseudotimeKernel>]
```

Kernels can also be inverted (i.e. the `backward`

attribute is set to the opposite value to the current one).
Note that this operation does *NOT* create a copy and modifies the kernel inplace, most importantly, the computed
transition matrix is removed. This makes it more easier to recompute the transition matrix of kernels,
since the handles point to the original objects.

Note that in the 2nd `print()`

statement, we access the private attribute - that’s because accessing
`cellrank.tl.kernels.Kernel.transition_matrix`

computes the transition matrix with default values.
This happens only with basic kernels and not the kernel expressions and only if they are not part of a
larger expression.

```
ck.compute_transition_matrix()
print(ck.transition_matrix is not None)
inv_ck = ~ck
print(ck._transition_matrix is not None)
print(inv_ck is ck)
```

Out:

```
True
False
True
```

We can also easily copy the kernel objects.

```
vk.compute_transition_matrix(
mode="deterministic", softmax_scale=4, show_progress_bar=False
)
print(vk.transition_matrix is not None)
inv_vk = ~(vk.copy())
print(vk._transition_matrix is not None)
print(vk is inv_vk)
```

Out:

```
True
True
False
```

After the transition matrix is computed, we can inspect the parameters used in its computation.

```
ck.compute_transition_matrix()
ck.params
```

Out:

```
{'dnorm': True, 'key': 'connectivities'}
```

The transition matrix can be written to `anndata.AnnData`

object. It is saved in the `.obsp`

attribute.
This also writes the parameters to the `.uns`

attribute.

```
ck.write_to_adata(key="transition_matrix")
adata.obsp["transition_matrix"]
```

Out:

```
<2531x2531 sparse matrix of type '<class 'numpy.float64'>'
with 102924 stored elements in Compressed Sparse Row format>
```

Precomputed kernels are useful if you have a transition matrix that was computed outside of CellRank that you would like to analyze using one of our estimators. It’s essentially an interface to CellRank’s estimators.

Below we supply a transition matrix saved in `adata.obsp["transition_matrix"]`

, but `anndata.AnnData`

object
is not required and we can just supply either `numpy`

or `scipy.sparse`

array. In that case, a minimal
empty `anndata.AnnData`

object is created, as shown below.

```
pk = cr.tl.kernels.PrecomputedKernel(adata.obsp["transition_matrix"])
pk.adata
```

Out:

```
AnnData object with n_obs × n_vars = 2531 × 1
```

**Total running time of the script:** ( 0 minutes 7.230 seconds)

**Estimated memory usage:** 141 MB