Generating user-specific database produces psedo-interactions that are not passed in.

[macelik]

Hello, I am building a custom CellPhoneDB database, but I'm encountering a problem where numerous pairs that are not present in my interactions.csv file are appearing in the generated database, and many actual pairs are missing. I have like 7000 pairs in my interaction file.

The code I am using to generate is here:

cellphonedb database generate --user-interactions combined_interactions.csv --user-interactions-only --user-protein prot_user.csv --user-gene gene_user.csv --result-path combined8

I have an interaction table which looks like below:

partner_a	partner_b	protein_name_a	protein_name_b	annotation_strategy	source
A0A1B0GTJ6	P22888	LOC101059948	LHCGR	user_curated	user
A4D1S0	O96014	WNT11	KLRG2	user_curated	user
A4D1S0	P41273	TNFSF9	KLRG2	user_curated	user

my protein.csv file looks like below

uniprot	protein_name
P01023	A2M_HUMAN
Q07954	LRP1_HUMAN
Q16613	AANAT_HUMAN

and gene table: If an ID did not have a corresponding ensemblID, I just make up one to keep it. such as ENSG0000000001, ENSG0000000002 etc

gene_name	uniprot	hgnc_symbol	ensembl
A2M	P01023	A2M	ENSG00000175899
LRP1	Q07954	LRP1	ENSG00000123384
AANAT	Q16613	AANAT	ENSG00000129673

[macelik]

Hi again, so it turns out, this issue occurs when both the protein and ligand are either ligands or receptors.

Is there any way to force CellPhoneDB to keep the edges in my input list as they are, without reversing them? I have already tried specifying the edges in my input file in a specific order (e.g., protein A first, protein B second), but this does not seem to prevent the edges from being reversed.

[luzgaral]

Hi,

Apologies but since CellphoneDB does not use interaction directionality (-> or <-) and the order of the proteins does not alter the results, CellphoneDB does not force order preservation when processing the user input database.

We understand that you would always like to see ligand as proteinA and receptor as proteinB, but rest assured that this will not impact the results as all the possible combinations are always tested (See the image here).

Hope this helps,

Luz