Can Nebula do multi-level comparisons?

[MANZHAOHUI]

For example, two treatments and control with several covariates.
Thank you.

[lhe17]

Hi Zhaohui, Yes, it can. You could treat your control as the reference level and use dummy coding for your two treatments. By running NEBULA, you can get their logFCs, say logFC_1 and logFC_2. Then, you can use their p-values in the output for testing a non-zero logFC_1 for treatment 1 and do the same for treatment 2. If you want to test logFC_1=logFC_2, then you need to output the covariance matrix of logFCs. Please refer to this section https://github.com/lhe17/nebula#testing-contrasts for more details about how to get the covariance matrix for testing contrasts. The example in the vignette tests logFC_1=logFC_2. If you want to test logFC_1=logFC_2=0 (i.e., two treatments and control are the same), once you get the covariance matrix, you can run a chisq omnibus test, like the one used in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061751/. I'll also add this example to the vignette in the next version. I hope this helps. Best regards, Liang

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[MANZHAOHUI]

Thank you for the explanation. It's very helpful.