Application of Sparse Linear Discriminant Analysis and Elastic Net for Diagnosis of IgA Nephropathy: Statistical and Biological Viewpoints
Background
IgA nephropathy (IgAN) is the most common primary glomerulonephritis diagnosed based on renal biopsy. Mesangial IgA deposits along with the proliferation of mesangial cells are the histologic hallmark of IgAN. Non-invasive diagnostic tools may help to prompt diagnosis and therapy. The discovery of potential and reliable urinary biomarkers for diagnosis of IgAN depends on applying robust and suitable models. Applying two multivariate modeling methods on a urine proteomic dataset were obtained from IgAN patients, and comparison of the results of these methods were the purpose of this study.


Methods
Two models were constructed for urinary protein profiles of 13 patients and 8 healthy individuals, based on sparse linear discriminant analysis (SLDA) and elastic net (EN) regression methods. A panel of selected biomarkers with the best coefficients were proposed and further analyzed for biological relevance using functional annotation and pathway analysis.


Results
Transferrin, α1-antitrypsin, and albumin fragments were the most important up-regulated biomarkers, while fibulin-5, YIP1 family member 3, prasoposin, and osteopontin were the most important down-regulated biomarkers. Pathway analysis revealed that complement and coagulation cascades and extracellular matrix-receptor interaction pathways impaired in the pathogenesis of IgAN.


Conclusion
SLDA and EN had an equal importance for diagnosis of IgAN and were useful methods for exploring and processing proteomic data. In addition, the suggested biomarkers are reliable candidates for further validation to non-invasive diagnose of IgAN based on urine examination.
['Mohammadi Majd|Tahereh|T|', 'Kalantari|Shiva|S|', 'Raeisi Shahraki|Hadi|H|', 'Nafar|Mohsen|M|', 'Almasi|Afshin|A|', 'Samavat|Shiva|S|', 'Parvin|Mahmoud|M|', 'Hashemian|Amirhossein|A|']
D000293:Adolescent D000328:Adult D015415:Biomarkers D030541:Databases, Genetic D016002:Discriminant Analysis D005260:Female D005922:Glomerulonephritis, IGA D006801:Humans D008297:Male D008875:Middle Aged D040901:Proteomics D055815:Young Adult
IgA nephropathy Biomarker Proteomics