In general, I recommend against interpreting the fraction of variance explained by residuals. This fraction is driven by:
If you have additional variables that explain variation in measured gene expression, you should include them in order to avoid confounding with your variable of interest. But a particular residual fraction is not ‘good’ or ‘bad’ and is not a good metric of determining whether more variables should be included.
See GitHub page for up-to-date responses to users’ questions.
## R version 4.5.1 Patched (2025-08-23 r88802)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 24.04.3 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.22-bioc/R/lib/libRblas.so 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.12.0  LAPACK version 3.12.0
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## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C               LC_TIME=en_GB             
##  [4] LC_COLLATE=C               LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                  LC_ADDRESS=C              
## [10] LC_TELEPHONE=C             LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## time zone: America/New_York
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## loaded via a namespace (and not attached):
##  [1] digest_0.6.37     R6_2.6.1          fastmap_1.2.0     xfun_0.53         cachem_1.1.0     
##  [6] knitr_1.50        htmltools_0.5.8.1 rmarkdown_2.30    lifecycle_1.0.4   cli_3.6.5        
## [11] sass_0.4.10       jquerylib_0.1.4   compiler_4.5.1    tools_4.5.1       evaluate_1.0.5   
## [16] bslib_0.9.0       yaml_2.3.10       rlang_1.1.6       jsonlite_2.0.0