A Nanopore Protein Sequencing Reply

Oct 28, 2025

Over on LinkedIn, someone posted the following:

I’ve written about most of these points elsewhere but thought it would be useful to put this all together in one place. So here we go.

Do nanopore-based proteomics platforms reach levels of accuracy that enable de novo protein sequencing?

No. This is very unlikely in the first instance in my view. It will just be difficult to fit the number of states in the available current ranges (also see here, and here). Processing the proteins (e.g. by expansion) may help.

But de novo, single molecule protein sequencing in a first product isn’t very likely.

More importantly it is probably an unnecessary high barrier to entry and a product that had sufficient throughput, but worked on an ensemble or fingerprinting basis would already be ready to enter the market.

Do Nanopore approaches offer meaningful scale and cost advantages?

No. Currently nanopore sequencing likely has the highest cost-of-goods per base of any available DNA sequencing technology.

The only way I could currently see this not being the case would be an expansion based approach. Here the same approach Roche have suggested for sequencing might be applied to protein sequencing.

Can nanopore reach sufficient precision on PTMs etc?

It’s still not 100% that we will be able to obtain any practically useful protein sequence information from nanopores.

But I’m leaning toward yes.

Broadly. Protein sequencing applications seem more like counting than de novo sequencing. Counting the percentage of protein X that has a PTM at position Y seems tractable.

Being able to identify with high accuracy, the de novo sequencing of a single protein… seems less practical.

Summary

To be successful over competing protein sequencing techniques, nanopore approaches will need an accuracy/quality advantage. If it only performs equally well as a fluorescent readout system, then nanopores will likely lose out on scale and cost-of-goods.