sci-RegulatoryClusteringModel Mac M1 version

Tutorial

See R tutorial in the vignettes folder.

If you want to read more about how SiRCle works, please check out our paper: https://www.biorxiv.org/content/10.1101/2022.07.02.498058v1

Install

R

Just install direcly in R, this will work for Windows and Mac (and probably Linux).

#install.packages("devtools")
library(devtools)
install_github("ArianeMora/SiRCleR_M1")
library(sircleM1)

Windows

Note if you are running Windows you might have an issue with long paths, to fix this please you can resolve this in the registry on Windows 10 (Computer Configuration > Administrative Templates > System > Filesystem > Enable Win32 long paths). If you have a different version of Windows, just google "Long paths fix" and your Windows version.

Mac with an M1 chip (new versions 2022)

If you are using a Mac with an M1 chip please see our M1 R version of the package (https://github.com/ArianeMora/SiRCleR_M1), it only has the regulatory clustering component, you will need to use python for the VAE component because of how the chip works with tensorflow.

Other dependencies

If you are using the visualisations for the over representation analysis you will need to install the following tools (also cite them!)

CRAN packages

install.packages('ggnewscale')

Biocmanager packages

if (!require("BiocManager", quietly = TRUE))
    install.packages("BiocManager")
BiocManager::install("enrichplot")
BiocManager::install("org.Hs.eg.db")
BiocManager::install("clusterProfiler")

Also while we have done our best to ensure all the dependencies are documented, if they aren't please let us know! And we will try to resolve them :)

Run

See the vignettes folder for a proper tutorial with data included that you can run!

Making your CpGs map to a single gene version

This is only in python at the moment if you're interested in this post an issue and I'll work on adding this to the R version :)

Signature Regulatory Clustering model

The general table of how we define regulatory clusters.

Methylation	RNAseq	Proteomics	Regulation driver_1	Regulation driver_2	Regulation_Grouping1	Regulation_Grouping2	Regulation_Grouping3
Hypermethylation	DOWN	DOWN	Methylation increase (MDS)	None	MDS	MDS	MDS
Hypermethylation	UP	DOWN	mRNA increase (TPDE)	Protein decrease (TMDS)	TPDE+TMDS	TPDE+TMDS	TMDS
Hypermethylation	UP	UP	mRNA increase (TPDE)	None	TPDE	TPDE	TPDE
Hypermethylation	DOWN	UP	Methylation increase (MDS)	Protein increase (TMDE)	MDS+TMDE	TMDE	TMDE
Hypermethylation	No Change	UP	mRNA increase (TPDE)	Protein increase (TMDE)	TPDE+TMDE	TMDE	TMDE
Hypermethylation	No Change	DOWN	mRNA increase (TPDE)	Protein decrease (TMDS)	TPDE+TMDS	TMDS	TMDS
Hypermethylation	UP	No Change	mRNA increase (TPDE)	Protein decrease (TMDS)	TPDE+TMDS	TPDE+TMDS	TMDS
Hypermethylation	DOWN	No Change	Methylation increase (MDS)	Protein increase (TMDE)	MDS+TMDE	MDS+TMDE	TMDE
Hypermethylation	No Change	No Change	Methylation increase (ncRNA)	None	MDS-ncRNA	MDS_ncRNA	MDS_ncRNA
Hypomethylation	DOWN	DOWN	mRNA decrease (TPDS)	None	TPDS	TPDS	TPDS
Hypomethylation	UP	DOWN	Methylation decrease (MDE)	Protein decrease (TMDS)	MDE+TMDS	TMDS	TMDS
Hypomethylation	UP	UP	Methylation decrease (MDE)	None	MDE	MDE	MDE
Hypomethylation	DOWN	UP	mRNA decrease (TPDS)	Protein increase (TMDE)	TPDS+TMDE	TPDS+TMDE	TMDE
Hypomethylation	No Change	UP	mRNA decrease (TPDS)	Protein increase (TMDE)	TPDS+TMDE	TMDE	TMDE
Hypomethylation	No Change	DOWN	mRNA decrease (TPDS)	Protein decrease (TMDS)	TPDS+TMDS	TMDS	TMDS
Hypomethylation	UP	No Change	Methylation decrease (MDE)	Protein decrease (TMDS)	MDE+TMDS	MDE+TMDS	TMDS
Hypomethylation	DOWN	No Change	mRNA decrease (TPDS)	Protein increase (TMDE)	TPDS+TMDE	TPDS+TMDE	TMDE
Hypomethylation	No Change	No Change	Methylation decrease (ncRNA)	None	MDE+ncRNA	MDE_ncRNA	MDE_ncRNA
No Change	DOWN	UP	mRNA decrease (TPDS)	Protein increase (TMDE)	TPDS+TMDE	TPDS+TMDE	TMDE
No Change	UP	DOWN	mRNA increase (TPDE)	Protein decrease (TMDS)	TPDE+TMDS	TPDE+TMDS	TMDS
No Change	DOWN	DOWN	mRNA decrease (TPDS)	None	TPDS	TPDS	TPDS
No Change	UP	UP	mRNA increase (TPDE)	None	TPDE	TPDE	TPDE
No Change	No Change	UP	Protein increase (TMDE)	None	TMDE	TMDE	TMDE
No Change	No Change	DOWN	Protein decrease (TMDS)	None	TMDS	TMDS	TMDS
No Change	UP	No Change	mRNA increase (TPDE)	Protein decrease (TMDS)	TPDE+TMDS	TPDE+TMDS	TMDS
No Change	DOWN	No Change	mRNA decrease (TPDS)	Protein increase (TMDE)	TPDS+TMDE	TPDS+TMDE	TMDE
No Change	No Change	No Change	NoChange	NoChange	NoChange	NoChange	NoChange

Please post questions and issues related to sci-rcm on the Issues section of the GitHub repository.