**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Cisneros-Barroso E., Fundación Instituto de Investigación Sanitaria de las Islas Baleares, Palma, Illes Balears.

**Main Body of the Abstract**
Background: The study aims to validate MALDI-TOF for early A-ATTRv diagnosis using plasma samples, addressing the challenge of distinguishing carriers from healthy individuals.
Methods: Human plasma samples from Son Llàtzer University Hospital underwent C18 reversed-phase extraction using ZipTips for sample preparation. Samples were diluted 1:10 in 50 mM ammonium bicarbonate and digested with trypsin. Digested and non-digested samples were analysed by MALDI-TOF. Pre-processed spectra that passed the quality control and predictor filtering were used to develop and assess thirty predictive models. The five providing the best performance were selected: SVM, Partial Least Squares, Sparse LDA, Shrinkage Discriminant Analysis, and High Dimensional Discriminant Analysis. A 10-fold cross-validation re-sampling scheme was used for model performance assessment, statistical validation and model parameters tuning, preventing inclusion of patient replicates in the training and testing set of any fold. A majority-voting scheme applied to patient replicates classification assigns the predicted patient class. The performance of the models for digested and non-digested samples was evaluated and compared.
Results: Digested samples outperformed non-digested ones, showing 86% average accuracy when classifying healthy individuals versus carriers and 69% average accuracy predicting patients against carriers. Notably, non-digested samples posed challenges (average accuracy: 54%) in distinguishing carriers from healthy individuals.
Conclusion: The study reveals the significance of sample preparation methods, with digested samples showing improved prediction accuracy. Treatment-related proteomic changes potentially contributed to lower accuracy in discriminating carriers from patients in digested samples. Future analyses should explore correlations between treatment modalities and proteomic profiles, refining MALDI-TOF's applicability for ATTRv disease diagnosis.



Optimizing MALDI-TOF for Early Detection of A-ATTRv Disease: Insights from Predictive Models and Sample Preparations PC7 (#173)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.