Targeted proteomics informed by long-read RNA-sequencing reveals protein isoform expression associated with bone mineral density

Targeted IS-PRM mass spectrometry detected protein isoforms from 288 peptides representing 166 putative BMD-associated splice-derived isoforms in differentiating osteoprogenitor cells and primary MSCs.

• Why it matters: Genetic risk for complex traits often involves RNA splicing, but it is unclear whether splice events yield stable, distinct protein isoforms that can be validated at the protein level.
• What they did: The study used genetics-guided targeted MS, prioritizing isoforms by sQTL colocalization, and compared targeted acquisition with conventional DDA to recover isoform-informative peptides.
• The result: Targeted acquisition increased recovery of isoform-informative peptides, rescued splice events missed or sparsely sampled by global acquisition, and confirmed protein-level expression of genetically prioritized isoforms in patient-derived clinical material.

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