Frequently asked questions

Frequently asked questions#

This section contains answers to frequently asked questions. Don’t see what you’re looking for here? Feel free to check out our Discourse or chat with us directly on Zulip.

What is the difference between batch_key and categorical_covariate_keys?#

While both batch_key and categorical_covariate_keys are meant to be used for categorical covariates whose effects we want to regress out, they have support for different features. batch_key generally supports more features and should be used before categorical_covariate_keys if possible. In particular, batch_key supports the following compared to categorical_covariate_keys:

  • Used to specify the main technical effect in the data, such as the sequencing lab, lane, sequencing type, or dataset of origin, for example.

  • Support for per-category dispersion parameters by specifying dispersion="gene-batch" for models such as SCVI.

  • Support for flexible embedding modeling by specifying batch_representation="embedding".

  • Support for counterfactual decoding by specifying the transform_batch argument in methods such as get_normalized_expression.

  • For models where use_observed_lib_size=False can be set, the model will treat the library size as a learned parameter, where the variational prior is set to a normal distribution with mean and variance computed per-batch.

On the other hand, categorical_covariate_keys supports the following features compared to batch_key:

  • Definition of multiple covariates at once (e.g., categorical_covariate_keys=["assay_type", "donor"]).

They also share some features:

  • One-hot encoded by default

  • Only passed into the decoder by default, and have the same behavior when specifying encode_covariates and deeply_inject_covariates.

  • Meant to capture technical nuisance effects.

My model errors out during training due to NaNs - how can I fix this?#

There is no straightforward solution sicne these are usually caused by numerical instabilities, but here are several factors to consider:

  • Data quality: Ensure that the data is appropriately preprocessed (e.g. removing cells/spots with low counts).

  • Data distribution: Ensure that, if the model expects raw counts (e.g. scVI), the data is not normalized or transformed in any way. This often means passing in the correct layer argument to the setup_anndata method.

  • Training parameters: You may need to adjust parameters such as the learning rate or batch size to stabilize training, or use gradient clipping to prevent exploding gradients.

  • Model activations: Some models contain exponential activations due to reproducibility reasons, which may be sometimes numrically unstable. Consider using another activation such as the softplus for more stability.

  • Adversarial training: For models with adversarial training (e.g. totalVI), consider turning off the component to see if the issue is resolved.

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