Oral Presentation 31st Annual Lorne Proteomics Symposium 2026

RDMS.app – An online platform for the interrogation and visualisation of rare disease proteomics data. (133124)

Nikeisha J Caruana 1 , Daniella H Hock 1 2 , Liana Semcesen 1 , Tanavi Sharma 1 , John Christodoulou 2 3 , David Thorburn 2 , David A Stroud 1 2 4
  1. Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria, Australia
  2. Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
  3. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  4. Victorian Clinical Genetic Services, Royal Children's Hospital, Melbourne, Victoria, Australia

Proteomics, leveraging mass spectrometry, offers a transformative approach to rare disease diagnosis by enabling the functional analysis of thousands of proteins in a single test. While genomic sequencing remains central to rare disease diagnostics, its 50% success rate highlights the need for complementary technologies. Mass spectrometry addresses this gap but brings distinct bioinformatics challenges such as incomplete protein coverage and data variability. Unlike genomics, which maps directly to a reference genome, proteomics demands tailored computational strategies, dynamic range management, and instrument variability considerations.

Our solution, rdms.app (Rare Disease Mass Spectrometry), integrates these proteomics challenges into a streamlined diagnostic workflow. This platform allows clinicians and researchers to analyse clinical proteomics data efficiently. Key features include the Relative Complex Abundance (RCA) analysis, which quantifies protein abundances, pinpointing defects in protein complexes. Benchmarking RCA against traditional enzymology revealed greater visual and statistical insights, enhancing diagnostic accuracy. To complement rdms.app, additional tools have been developed including the PDBPainter, and RangeFinder. PDBPainter generates topographical heatmaps, illustrating protein changes within complex structures from the Protein Data Bank, aiding in visualising disorder impacts on proteins and their interactions. RangeFinder presents a focused view on specific protein abundance, comparing patient data to control medians for clearer diagnostic contexts and is particularly useful when comparing trio (e.g paediatric + two adult) clinical samples.

While originally designed for mitochondrial disease investigation, expansion of the rdms.app to all protein complex investigations has begun with an additional integrated application, Complexity, automatically targeting complexes in proteomics data and allowing researchers to generate RCA plots and topographical heatmaps on any human proteomics data they have acquired.

The rdms.app framework has contributed to diagnosing over 60 patients, embedding RCA, PDBPainter, and RangeFinder results into clinical reports. By providing a comprehensive, user-friendly interface, rdms.app allows the integration of proteomics into rare disease diagnostics, promising improved patient diagnostic outcomes.

  1. Hock, D.H., Caruana, N.J., Semcesen, L.N. et al. Untargeted proteomics enables ultra-rapid variant prioritisation in mitochondrial and other rare diseases. Genome Med 17, 58 (2025).