Diagnostic
Developments and Applications of Functional Protein MicroarraysFunctional protein microarray is a crucial tool in the study of proteins in native, unbiased, and high-throughput manner. There is a wide variety of applications, including the study of proteome-wide molecular interactions, analysis of post-translational modifications, identification of novel drug targets, and examination of pathogen-host interactions. Functional protein microarray is also useful in profiling antibody specificity, as well as in the discovery of novel biomarkers, especially for autoimmune diseases, infectious diseases, and cancers. Recently, the virion display method has been applied to produce functional GPCR array for various research and pharmaceutical applications.
Identification of a Multiplex Biomarker Panel for Hypertrophic Cardiomyopathy Using Quantitative Proteomics and Machine LearningExploratory myocardial and plasma proteomics screens in patients with hypertrophic cardiomyopathy identified new biomarkers that were developed into a multiplexed targeted liquid chromatography-tandem/mass spectrometry-based assay for validation across a larger cohort of patients with this disease. Using quantitative proteomics and supervised machine learning, this six-biomarker panel shows a relationship with myocardial substrate changes in patients with hypertrophic cardiomyopathy and with their estimated sudden cardiac death risk.
Proteomic Maps of Human Gastrointestinal Stromal Tumor SubgroupsQuantitative proteome profiling of GIST from 13 patients classified into very low/low, intermediate and high-risk subgroups were performed. An extended cohort of GIST (n = 131) was used for immunohistochemical validation of proteins of interest. Functional insights into proteins associated with GIST risk grade were assessed. Immunohistochemical analysis revealed that GIST patients with high PTPN1 had low chances of developing metastasis. This work provides valuable information for understanding the inherent biology and evolution of GIST.
Proteome Analysis of Human Neutrophil Granulocytes From Patients With Monogenic Disease Using Data-independent AcquisitionData-independent acquisition proteomics was used to study proteome changes of naive human neutrophils in rare monogenic diseases affecting their functions. Neutrophils of patients with mutations in the neutrophil elastase gene ELANE demonstrated global proteome dysregulation, whereas chronic granulomatous disease and leukocyte adhesion deficiency had modest effects on the respective neutrophil proteomes. Proteomics then guided targeted genetic assays to resolve two clinical cases with undetermined genetic causes, highlighting the usefulness of mass spectrometry-based clinical diagnostics.