Mageck RuntimeWarning overflow encountered in multiply

Question

[liz.b]

I'm trying to run mageckMLE analysis, but the analysis is running very quickly and giving the following warning whilst running permutations:

INFO  @ Wed, 20 Aug 2025 16:01:22: Thread 0: Calculating TAAR1 (1) ...
/package/python-cbrg/current/3.11.3/lib/python3.11/site-packages/mageck/mleem.py:70: RuntimeWarning: overflow encountered in multiply
  mu_sq=np.multiply(mu_estimate,mu_estimate)
/package/python-cbrg/current/3.11.3/lib/python3.11/site-packages/mageck/mleem.py:73: RuntimeWarning: invalid value encountered in divide
  nb_r=np.divide(mu_sq,var_vec-mu_estimate)
/package/python-cbrg/current/3.11.3/lib/python3.11/site-packages/mageck/mleem.py:71: RuntimeWarning: overflow encountered in multiply
  var_vec=mu_estimate+np.multiply(alpha, mu_sq)
INFO  @ Wed, 20 Aug 2025 16:03:59: Thread 0: Calculating PCBD1 (1001) ...

I'm running a mageck MLE analysis on 5 samples and a library of 2000 genes, using a list of negative control genes as the normalisation method. The counts files look normal to me. It seems to be reading in the design matrix etc fine. It was having an issue with the negative control sgRNAs, but that seems to have been fixed using --max-sgrnapergene-permutation set to 105 and I still get the same warning. ChatGPT suggested that it could be due to having read counts for some genes/samples 10x greater than the median, but I don't want to exclude a lot of genes just for having a lot of reads...

Does anyone know what might be the cause or solution?

[ATpoint]

At least show your command line and a head of the files you give to the tool. These internal warning messages are not helpful.