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 4.6.0 (2026-04-24)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 24.04.4 LTS
##
## Matrix products: default
## BLAS: /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3
## LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/libopenblasp-r0.3.26.so; LAPACK version 3.12.0
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## locale:
## [1] LC_CTYPE=en_US.UTF-8 LC_NUMERIC=C LC_TIME=en_US.UTF-8
## [4] LC_COLLATE=en_US.UTF-8 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: Etc/UTC
## tzcode source: system (glibc)
##
## attached base packages:
## [1] stats graphics grDevices utils datasets methods base
##
## other attached packages:
## [1] edgeR_4.10.0 pander_0.6.6 variancePartition_1.42.0
## [4] BiocParallel_1.46.0 limma_3.68.1 ggplot2_4.0.3
## [7] knitr_1.51 rmarkdown_2.31
##
## loaded via a namespace (and not attached):
## [1] tidyselect_1.2.1 dplyr_1.2.1 farver_2.1.2 S7_0.2.2
## [5] bitops_1.0-9 fastmap_1.2.0 digest_0.6.39 lifecycle_1.0.5
## [9] statmod_1.5.1 magrittr_2.0.5 compiler_4.6.0 rlang_1.2.0
## [13] sass_0.4.10 tools_4.6.0 yaml_2.3.12 labeling_0.4.3
## [17] plyr_1.8.9 RColorBrewer_1.1-3 KernSmooth_2.23-26 withr_3.0.2
## [21] purrr_1.2.2 numDeriv_2016.8-1.1 BiocGenerics_0.58.0 sys_3.4.3
## [25] grid_4.6.0 aod_1.3.3 caTools_1.18.3 scales_1.4.0
## [29] gtools_3.9.5 iterators_1.0.14 MASS_7.3-65 cli_3.6.6
## [33] mvtnorm_1.3-7 reformulas_0.4.4 generics_0.1.4 reshape2_1.4.5
## [37] minqa_1.2.8 cachem_1.1.0 stringr_1.6.0 splines_4.6.0
## [41] parallel_4.6.0 matrixStats_1.5.0 vctrs_0.7.3 boot_1.3-32
## [45] Matrix_1.7-5 jsonlite_2.0.0 pbkrtest_0.5.5 maketools_1.3.2
## [49] locfit_1.5-9.12 jquerylib_0.1.4 tidyr_1.3.2 snow_0.4-4
## [53] glue_1.8.1 nloptr_2.2.1 codetools_0.2-20 stringi_1.8.7
## [57] gtable_0.3.6 EnvStats_3.1.0 lme4_2.0-1 lmerTest_3.2-1
## [61] tibble_3.3.1 remaCor_0.0.20 pillar_1.11.1 htmltools_0.5.9
## [65] gplots_3.3.0 R6_2.6.1 Rdpack_2.6.6 evaluate_1.0.5
## [69] lattice_0.22-9 Biobase_2.72.0 rbibutils_2.4.1 backports_1.5.1
## [73] RhpcBLASctl_0.23-42 broom_1.0.12 fANCOVA_0.6-1 corpcor_1.6.10
## [77] bslib_0.10.0 Rcpp_1.1.1-1.1 nlme_3.1-169 xfun_0.57
## [81] buildtools_1.0.0 pkgconfig_2.0.3