Description Usage Arguments Details Value References See Also Examples

This function fits a Latent Dirichlet Allocation (LDA) to single-cell RNA-seq data.

1 2 3 |

`data` |
A matrix of (non-negative) RNA-seq expression levels where each row is a gene and each column is the cell sequenced. |

`method` |
LDA inference method to use. Can be any unique prefix of ‘maptpx’, ‘Gibbs’ or ‘VEM’ (defaults to ‘maptpx’) |

`k.topics` |
Integer (optional). Number of topics to fit in the model. If |

`log.scale` |
Boolean (optional). Whether the data should be log-scaled. |

`sd.filter` |
Numeric or |

`tot.iter, tol` |
Numeric parameters (optional) forwarded to the chosen LDA inference method's contol class. |

Latent Dirichlet allocation (LDA) is a generative model that allows sets of observations to be explained by unobserved groups (topics) that explain why some parts of the data are similar [Blei, 2003]. Each topic is modelled as a (Dirichlet) distribution over observations and each set of observations is also modelled as a (Dirichlet) distribution over topics. In lieu of the traditional NLP context of word occurence counts in documents, our model uses RNA-seq observation counts in single cells. Three separate LDA inference methods can be used at the moment:

Gibbs uses Collapsed Gibbs Sampling method (implemented by Xuan-Hieu Phan and co-authors in the topicmodels package [Phan, 2008]) to infer the parameters of the Dirichlet distributions for a given number of topics. It gives high accuracy but is very time-consuming to run on large number of cells and genes.

VEM uses Variational Expectation-Maximisation (as described in [Hoffman, 2010]). This method tends to converge faster than Gibbs collapsed sampling, albeit with lower accuracy.

maptpx uses the method described in [Taddy, 2011] and implemented in package maptpx to estimate the parameters of the topic model for increasing number of topics (using previous estimates as a starting point for larger topic numbers). The best model (/number of topics) is selected based on Bayes factor over the Null model. Although potentially less accurate, this method provides the fastest way to train and select from a large number of models, when the number of topics is not well known.

When in doubt, the function can be ran with its default parameter values and should produce a usable LDA model in reasonable time (using the ‘maptpx’ inference method). The model can be further refined for a specific number of topics with slower methods. While larger models (using large number of topics) might fit the data well, there is a high risk of overfitting and it is recommended to use the smallest possible number of topics that still explains the observations well. Anecdotally, a typical number of topics for cell differentiation data (from pluripotent to fully specialised) would seem to be around 4 or 5.

A LDA model fitted for `data`

, of class LDA-class (for methods 'Gibbs' or 'VEM') or topics (for 'maptpx')

Blei, Ng, and Jordan. “Latent dirichlet allocation.” the Journal of machine Learning research 3 (2003): 993-1022.

Hoffman, Blei and Bach (2010). “Online Learning for Latent Dirichlet Allocation.” In J Lafferty, CKI Williams, J Shawe-Taylor, R Zemel, A Culotta (eds.), Advances in Neural Information Processing Systems 23, pp. 856-864. MIT Press, Cambridge, MA.

Hornik and Grün. “topicmodels: An R package for fitting topic models.” Journal of Statistical Software 40.13 (2011): 1-30.

Phan, Nguyen and Horiguchi. “Learning to classify short and sparse text & web with hidden topics from large-scale data collections.” Proceedings of the 17th international conference on World Wide Web. ACM, 2008.

Taddy. “On estimation and selection for topic models.” arXiv preprint arXiv:1109.4518 (2011).

LDA, topics, LDA_Gibbscontrol-class, CTM_VEMcontrol-class

1 2 3 4 5 6 7 8 9 10 11 12 13 | ```
# Load skeletal myoblast RNA-Seq data from HSMMSingleCell package:
library(HSMMSingleCell)
data(HSMM_expr_matrix)
# Run LDA inference using 'maptpx' method for k = 4:
lda.results = compute.lda(HSMM_expr_matrix, k.topics=4, method="maptpx")
# Run LDA inference using 'maptpx' method for number of topics k = 3 to 6:
lda.results = compute.lda(HSMM_expr_matrix, k.topics=3:6, method="maptpx")
# Run LDA inference using 'Gibbs' [collapsed sampling] method for number of k = 4 topics:
lda.results = compute.lda(HSMM_expr_matrix, k.topics=4, method="Gibbs")
``` |

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