An Artificial Antibody-Based Toolbox Accelerates Validation of Hidden Microproteins Encoded by the Dark Genome - PubMed

4 hours ago

Microproteins encoded by small open reading frames are a pivotal blind spot in conventional protein-coding assumptions.
The annotation of the 'dark proteome' is time- and labor-consuming due to limitations in existing validation methods.
CLAIMID, a comprehensive toolbox, was developed for accelerated and ultrasensitive validation of microproteins at multiple biological scales.
Molecularly imprinted polymers (MIPs) serve as the core of CLAIMID, offering ultrasensitive and precise annotation combined with surface-enhanced Raman scattering (SERS) detection.
MIPs exhibit excellent specificity, comparable to antibodies, and high anti-interference against biological matrices.
CLAIMID enables rigorous validations at multiple scales (single cells, cell populations, tissues) and diverse detection formats (SERS-based immunoassay, imaging, mass spectrometric identification).
Four predicted microproteins were confirmed at the protein level across various cell lines, with three identified as potential tumor biomarkers.
CLAIMID presents an annotation toolbox with unparalleled efficiency, sensitivity, and scalability, advancing microprotein biology.

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