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cbravo93 avatar cbravo93 commented on July 1, 2024

Hi @helenhuangmath !

I think I just answered this by email, but here it goes:

0- Based on the top above left (likelihood per iteration plot), I would increase the number of burning iterations. For the models with higher number of topics (from 35 on), your likelihood is not stabilized when starting the sampling (this can effect you model selection and results). Maybe 300 burn-in, or even a bit higher would be better.

1a- We have seen that in some datasets it seems more like the curve reach a stable likelihood rather than go down again after maximum. In this case, you can try with the most simple model which has a similar likelihood. For your data, I would maybe add some models (10,20,30) to make sure it is not around there.

1b- I would check the correlation between the scores (topic-cell, region-topic) before merging, and would be careful with downstream analyses (these correlated topics, how much do the regions on them overlap?). If you opt for merging them, then do it on the assignment matrices [for topic-cell and region-topic, respectively: [email protected]$document_expects & [email protected]$topics], and the rest of the functions/normalizations should work. I can help with the code for this, just let me know :).

  1. Normally, binarised topics are around couple thousands regions; but this depends on the thresholds for binarisation you choose. I don’t like thresholds and prefer to work with the probabilities themselves when possible. Normally, regions that are not in topics are because they are generally lowly accessible (can you check the number of cells in which topic regions vs non-topic regions are accessible? And also check the binarisation plots). If you prefer to work with differentially accessible regions, you can also use the predictive distribution matrix (with probabilities of the regions in cells), and run e.g. a wilcoxon test between whatever groups. Also with this matrix, you can look for the accessibility probability of regions of interest (whether they are in a topic or not, this is quite interesting :P).

I hope this is useful, and let me know if you have more questions :)!

C

from cistopic.

helenhuangmath avatar helenhuangmath commented on July 1, 2024

Thank you so much again! It's quite helpful!

from cistopic.

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