I think there is a problem with TxDb.Hsapiens.UCSC.hg19.knownGene and EnsDb.Hsapiens.v75. I'm struggling to install all of these packages as they pause at byte-compile and prepare package for lazy loading . Can anyone try to re-install them in their local machine because am not the only one who is having the problem, please? They used to work fine until a week ago!

As usual, I install the packages by:

BiocManager::install(c("Homo.sapiens", "EnsDb.Hsapiens.v75", "TxDb.Hsapiens.UCSC.hg19.knownGene"))

I also tried installing them individually:


It pause at:

* installing *source* package ‘TxDb.Hsapiens.UCSC.hg19.knownGene’ ...
** using staged installation
** R
** inst
** byte-compile and prepare package for lazy loading

sessionInfo( )

R version 4.0.3 (2020-10-10)
Platform: x86_64-apple-darwin17.0 (64-bit)
Running under: macOS Big Sur 10.16

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRblas.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRlapack.dylib

[1] en_GB.UTF-8/en_GB.UTF-8/en_GB.UTF-8/C/en_GB.UTF-8/en_GB.UTF-8

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

loaded via a namespace (and not attached):
[1] BiocManager_1.30.10 compiler_4.0.3      tools_4.0.3    

I've tried with and without RStudio. I'd be grateful if someone can try to replicate the error, please?

  • $\begingroup$ Can you edit your question to include how you are trying to install the packages? thanks. $\endgroup$
    – user438383
    Jan 1, 2021 at 13:18
  • $\begingroup$ Sorry @user438383, I forgot to add how I installed the pacakges. I edited the question now and added more details. $\endgroup$
    – Sam
    Jan 1, 2021 at 13:27
  • $\begingroup$ Thanks. Just tried it on macOs 10.15 and it seems to have installed OK. Does the same problem occur if you try and install a different package via bioconductor, or a package using install.packages()? $\endgroup$
    – user438383
    Jan 1, 2021 at 13:33
  • $\begingroup$ Oh, thank you. This is extremely strange because I tried it on my friend's computer and had the same problem. I can install any other package via Bioconductor without problem except for these three. Can I ask if you installed all three of them? $\endgroup$
    – Sam
    Jan 1, 2021 at 13:37
  • $\begingroup$ It's been a week and I've tried uninstalling R, RStudio and RFrameworks countless times but still not working. I'm sorry but can I ask if if you used BiocManager::install(c("Homo.sapiens", "EnsDb.Hsapiens.v75", "TxDb.Hsapiens.UCSC.hg19.knownGene")) to install them? $\endgroup$
    – Sam
    Jan 1, 2021 at 13:39

1 Answer 1


I am able to successfully install these packages using:

BiocManager::install(c("Homo.sapiens", "EnsDb.Hsapiens.v75", "TxDb.Hsapiens.UCSC.hg19.knownGene"))

This completes without any errors / warnings (R v4.0.3 / macOS 10.16), so I don't believe the packages themselves/Bioconductor are 'broken', but I suspect you are having compiler issues due to the Big Sur update.

These are the steps I used to solve the problem:

  1. Reinstall xcode command line tools (even if it says "up to date")
sudo rm -rf /Library/Developer/CommandLineTools
sudo xcode-select --install
  1. Install gcc & llvm via Homebrew (instructions for installing Homebrew) or, if you already have gcc/llvm installed via Homebrew, skip to the next step
# This can take several hours
brew install gcc
brew install llvm
  1. Once you have gcc & llvm installed via Homebrew:
brew cleanup
brew update
brew upgrade
brew reinstall gcc
brew reinstall llvm
  1. Link some headers into /usr/local/include
sudo ln -s /Library/Developer/CommandLineTools/SDKs/MacOSX.sdk/usr/include/* /usr/local/include/

# You can safely ignore warnings like this:
#ln: /usr/local/include//tcl.h: File exists
#ln: /usr/local/include//tclDecls.h: File exists
#ln: /usr/local/include//tclPlatDecls.h: File exists
#ln: /usr/local/include//tclTomMath.h: File exists
#ln: /usr/local/include//tclTomMathDecls.h: File exists
#ln: /usr/local/include//tk.h: File exists
#ln: /usr/local/include//tkDecls.h: File exists
#ln: /usr/local/include//tkPlatDecls.h: File exists
  1. Create a new ~/.R/Makevars file (if you already have a ~/.R/Makevars file, save it in a different directory (away from ~/.R/)) and include only these lines in the file:
FLIBS=-L/usr/local/gfortran/lib/gcc/x86_64-apple-darwin19/10.2.0 -L/usr/local/gfortran/lib -lgfortran -lquadmath -lm

LLVM_LOC = /usr/local/opt/llvm
CC=/usr/local/gfortran/bin/gcc -fopenmp
CXX=/usr/local/gfortran/bin/g++ -fopenmp
CFLAGS=-g -O3 -Wall -pedantic -std=gnu99 -mtune=native -pipe
CXXFLAGS=-g -O3 -Wall -pedantic -std=c++11 -mtune=native -pipe
LDFLAGS=-L/usr/local/opt/gettext/lib -L$(LLVM_LOC)/lib -Wl,-rpath,$(LLVM_LOC)/lib
CPPFLAGS=-I/usr/local/opt/gettext/include -I$(LLVM_LOC)/include -I/Library/Developer/CommandLineTools/SDKs/MacOSX.sdk/usr/include
  1. Compile a package from source in R/Rstudio
# To check whether openmp is enabled, compile data.table:
install.packages("data.table", type = "source")
  1. If your package fails to compile, a couple of SO users have had to install a fresh gfortran (re: https://stackoverflow.com/a/65334247/12957340), which you can download from https://github.com/fxcoudert/gfortran-for-macOS/releases/tag/10.2-bigsur-intel

Once you can install packages from source without error/issue, update Bioconductor

BiocManager::install(version = "3.12")

Then, finally, you should be able to install your packages using

BiocManager::install(c("Homo.sapiens", "EnsDb.Hsapiens.v75", "TxDb.Hsapiens.UCSC.hg19.knownGene"))
  • $\begingroup$ You are amazing Jared, I'll go through the steps right now to see if it works, fingers crossed. $\endgroup$
    – Sam
    Jan 7, 2021 at 19:46
  • 1
    $\begingroup$ Awesome, it is working now. Thank you so much, Jared :) $\endgroup$
    – Sam
    Jan 16, 2021 at 2:12

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