What is Iterative Mapping?
Iterative Mapping is Nautilus’ novel method for quantifying proteins and proteoforms across the full proteome. In the method, billions of protein molecules are captured and displayed on massive, single-molecule arrays – one protein per optically distinguishable landing pad. Fluorescent probes that bind features indicative of protein or proteoform identity are sequentially added to the array, and multiple probe-protein binding events are recorded for every individual protein molecule. After tens to hundreds of unique probe binding cycles, machine learning-powered algorithms convert the probe binding patterns into confident protein and proteoform identifications that are summed for robust quantification.
What are the benefits of Iterative Mapping?
Unlike other methods, Iterative Mapping is designed to enable complete proteome coverage without compromising reproducibility, sensitivity and dynamic range due to:
- Single-molecule sensitivity and precision – other methods blur signals coming from many molecules and deliver rough estimates of abundance without the ability to identify proteoforms.
- Massive arrays capable of capturing the full proteome – other methods rarely quantify more than 50% of the proteome and often quantify different portions of the proteome in every sample.
- Multi-touch identifications compatible with diverse probe modalities that make quantitation accurate and reproducible – other methods make convoluted inferences about protein quantity from the detection of a few epitopes or peptides per protein yielding inaccurate and irreproducible protein quantifications.
Can you share examples demonstrating Iterative Mapping’s performance?
In our recent preprint, we demonstrated accurate, sensitive, precise, and highly reproducible quantitation of 130 tau proteoforms with just 12 probes. This work shows how all the components of our platform come together to quantify single-protein molecules and provide in-depth views of proteoform landscapes that cannot be seen on other platforms.
We regularly share updates on the application of Iterative Mapping to broadscale proteomics at conferences throughout the year. Access our US HUPO 2025 updates here – it features data demonstrating limited bias in protein library preparation, high sensitivity in protein quantification, and reproducibility in probe binding patterns.
When can I use Iterative Mapping in my work?
Please reach out to us if you’d like to use Iterative Mapping in your research, particularly if you’re interested in using our tau proteoform assay – we’re actively pursuing early-stage collaborations and would love to hear from you! Contact us here.
MORE ARTICLES
