Question: Harmony batch correction vs. regressing out donor effect in Seurat
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gravatar for Lucy
11 days ago by
Lucy20
Lucy20 wrote:

Hi,

I am performing combined analysis of three scRNA-seq samples from different donors generated using 10x Genomics technology. I am trying to decide whether to use Harmony (https://www.biorxiv.org/content/10.1101/461954v2) to remove donor effects or whether to regress out donor during the sctransform step (https://satijalab.org/seurat/v3.0/sctransform_vignette.html) in the Seurat pipeline.

What are the relative advantages and disadvantages of the two approaches?

Best wishes,

Lucy

ADD COMMENTlink modified 11 days ago by jared.andrews073.4k • written 11 days ago by Lucy20

You might also find this recent discussion helpful: about batch correction in scRNA-seq

ADD REPLYlink written 11 days ago by igor8.6k
1
gravatar for jared.andrews07
11 days ago by
jared.andrews073.4k
St. Louis, MO
jared.andrews073.4k wrote:

You should not use SCTransform to regress out batch effects. Rather, you should use one of Seurat's integration methods. Seurat also has a number of wrappers around different integration methods, including Harmony.

Personally, fastMNN has worked well for me, but it's usually worth trying a few methods, as they don't all perform similarly across all datasets.

ADD COMMENTlink written 11 days ago by jared.andrews073.4k

Thank you. What is the reason to not use SCTransform to regress out batch effects?

ADD REPLYlink written 11 days ago by Lucy20
1

The authors don't recommend it, as it's only meant to remove minor variation/biases due to differences in cell cycle, reads in mitochondrial genes, etc. rather than batch effects that affect every cell in a much more systemic manner. Their docs are a bit of a mess, so I can't find a specific reference, but if you dig around their github issues page, you can find threads that talk about it. Additionally, you can read their preprint about sctransform and/or their paper on integration specifically that shed more light on this.

ADD REPLYlink written 11 days ago by jared.andrews073.4k

Great, thanks for the help!

ADD REPLYlink written 11 days ago by Lucy20
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