High-resolution protein fragment interactions using AVA-Seq on a human reference set

Ramadan, S.; Aleksic, J.; Al-Thani, N. M.; Mohamoud, Y. A.; Hill, D. E.; Malek, J. A.

doi:10.1101/2021.07.28.454266

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bioRxiv · 10.1101/2021.07.28.454266

High-resolution protein fragment interactions using AVA-Seq on a human reference set

Ramadan, S.·Aleksic, J.·Al-Thani, N. M.·Mohamoud, Y. A.·Hill, D. E.·Malek, J. A.

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Abstract

Protein-protein interactions (PPIs) are important in understanding numerous aspects of protein function. Here, the recently developed all-vs-all sequencing (AVA-Seq) approach to determine protein-protein interactions was tested on a gold-standard human protein interaction set (hsPRS-v2). Initially, these data were interpreted strictly from a binary PPI perspective to compare AVA-Seq to other binary PPI methods tested on the same hsPRS-v2. AVA-Seq recovered 20 of 47 (43%) binary PPIs from this reference set comparing favorably with other methods. The same experimental data allowed for the determination of >500 known and novel PPIs including interactions between wildtype fragments of tumor protein p53 and minichromosomal maintenance complex proteins 2, and 5 (MCM2 and MCM5) that could be of interest in human disease. Additional results gave a better understanding of why interactions might be missed using AVA-Seq and aide future PPI experimental design for maximum recovery of information.

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Ramadan, S., Aleksic, J., Al-Thani, N. M., Mohamoud, Y. A., Hill, D. E., Malek, J. A.. 2021-07-29. High-resolution protein fragment interactions using AVA-Seq on a human reference set. https://doi.org/10.1101/2021.07.28.454266

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