A proteome-wide atlas of drug mechanism of action - Nature Biotechnology

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A proteome-wide atlas of drug mechanism of action - Nature Biotechnology
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A proteome-wide atlas of the effect of 875 compounds reveals mechanisms of action and off-target effects

) Number of PubMed citations per library compound, with select examples shown. Overlap of all annotated targets from the MOA library and all targets with an FDA approved drug. The list of FDA approved drug targets was acquired from The Human Protein Atlas Target redundancy for compounds in the library. 694 compounds are annotated to target a protein that is also targeted by another compound. 183 compounds target proteins that are unique among the library. All annotated targets were considered.

Representative plot comparing the Log2 FC values for two replicates of the control compound. The median Pearson correlation for two replicates of the control compound was 0.87, which is the correlation of the two replicates shown. Percent coefficient of variation protein level fold-change measurements across all 55 biological replicates . After merging/averaging two biological replicates , the Percent CV was recalculated .

, which is the same graph using a five standard deviation cutoff. Rate at which proteins increase versus decrease by five standard deviations. Proteins that mostly increase with small molecule treatments are in blue, those that mostly decrease in red. Only those proteins quantified in more than half of compound are shown . Change rate is calculated by taking the number of compounds affecting expression by five standard deviations and dividing by the compounds where the protein was quantified.

The 541 compound-target pairs analyzed, broken down by the two different regulation thresholds. Those in green and red are highlighted/annotated in Fig.

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