MALDI-TOF analysis of blood serum proteome can predict the presence of monoclonal gammopathy of undetermined significance

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia that can progress to malignant multiple myeloma (MM). Specific molecular biomarkers to classify the MGUS status and discriminate the initial asymptomatic phase of MM have not been identified. We examined the serum peptidome profile of MGUS patients and healthy volunteers using MALDI-TOF mass spectrometry and developed a predictive model for classifying serum samples. The predictive model was built using a support vector machine (SVM) supervised learning method tuned by applying a 20-fold cross-validation scheme. Predicting class labels in a blinded test set containing randomly selected MGUS and healthy control serum samples validated the model. The generalization performance of the predictive model was evaluated by a double cross-validation method that showed 88% average model accuracy, 89% average sensitivity and 86% average specificity. Our model, which classifies unknown serum samples as belonging to either MGUS patients or healthy individuals, can be applied to clinical diagnosis.

Prediction of malaria transmission drivers in Anopheles mosquitoes using artificial intelligence coupled to MALDI-TOF mass spectrometry

“…A recent study used a similar approach to distinguish between E. coli and Shigella species 21 . In clinical pathology, this strategy was applied to the blood serum proteome to predict the presence of monoclonal gammopathy of undetermined significance 30 and to discriminate between multiple myeloma patients and healthy donors 20 . In entomology, MALDI-TOF MS coupled with machine learning approaches has been tested to distinguish closely related Anopheles vector species 19 .…”

Rapid classification and prediction of COVID-19 severity by MALDI-TOF mass spectrometry analysis of serum peptidome

“…The preparation of the serum and the analysis of the samples by MALDI-TOF MS were performed as previously described (7). Serum samples were purified and concentrated using reversed phase C18 tip, Pierce™ C18, following the manufacture instructions.…”

Improved Screening of Monoclonal Gammopathy Patients by MALDI-TOF Mass Spectrometry

“…These results show an improvement in the detection rate of all isotypes of M proteins in MM patients when MALDI-TOF MS is used. In addition, Barceló et al have used the MALDI MS fingerprint of small proteome 2–10 kDa coupled with machine learning to predict the presence of monoclonal gammopathy with nearly 90% accuracy, sensitivity, and specificity . This suggests that spectral fingerprints can be used for diagnostics and discrimination of various monoclonal gammopathies using liquid biopsies.…”

“…Spectral profiling by MALDI-TOF MS can reveal informative molecular patterns and contribute to a better understanding of the biological background as well as diagnostics or follow-up of PCL and MM patients. Recently, several studies have implemented MALDI MS to monitor various biomarkers in monoclonal gammopathies. − In particular, abnormal immunoglobulin (M-protein) is produced in large quantities by malignant plasma cells in both MM and PCL patients. Detection and isotyping of the paraprotein by electrophoresis are common in clinical practice, but alternative methods including mass spectrometry have been successfully evaluated. − Eveillard et al.…”