Perturbation Project

[tonywu1999]

Aim of the project

The question of whether results of one perturbation experiment can be applied to predict the results of a future perturbation experiment in a different context remains a challenge in MS proteomics. For example, can we predict the effect of a gene knockout on protein abundance in a cell line in one lab based on how that drug affected the same cell line in another lab? This question remains a challenge since every MS proteomics experiment can have systematic differences, to the point where there is day to day variation within the same lab.

This project aims to formalize the framework for predicting the outcome of perturbations in future experiments based on past experiments. Some questions we aim to address include:

• Given perturbation data in one experiment, what conditions make it possible to predict the effect of a different perturbation for a new experiment?
• How similar must the experimental factors of 2 experiments be to ensure it is practical to transport insights from one context to another? e.g. transporting insights from one cell line to another cell line may be possible, but may not be as feasible between different organs or species.

Dataset Preferences

• We ideally would like datasets involving protein degraders or gene knockouts (i.e. any perturbation that directly affects protein abundance, so unfortunately not kinase inhibitors).
• To ease initial analysis, we focus on transportability of results across labs analyzing the same cell line (e.g. HEK293 seems popular)
• Datasets with high number of replicates, multiple perturbations, and/or multiple cell lines are preferred

Datasets

This table will be constantly updated with new datasets and order of preference for annotation.

PRIDE ID	Paper ID	Number of Replicates Per Group	Conditions	Cell Lines	Perturbation	Main Target	Acquisition Type
PXD053502	PMID39392888	3	drug/control	HEK293	MZ-1 (degrader)	BRD4	DIA
PXD047934	PMID38958654	3	drug1-4/control	HEK293	CC-885 (degrader), ACBI-8451+ACBI-0068 (synthesized degraders)	GSPT1, CDK4	TMT
PXD041200	N/A	4	drug/control	miniTurboID-CRBN HEK293 Flp-In	Lenalidomide (degrader)	CK1α	DIA
PXD041128	N/A	3	drug/control	TurboID-CRBN HEK293 Flp-In	CC-885 (degrader)	GSPT1	DIA
PXD041047	N/A	3	drug/control	TurboID-CRBN HEK293 Flp-In	pomalidomide (degrader)	ZF	DIA
PXD041097	N/A	4	drug/control	TurboID-CRBN HEK293 Flp-In	Thalidomide (degrader)	ZF	DIA
PXD041081	N/A	4	drug/control	TurboID-CRBN HEK293 Flp-In	Iberdomide (degrader)	IKZF1/IKZF3	DIA